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Objectives: General practitioners are trained to care for patients with a high level of responsibility and professional competency. However, there are few reports on the physical and mental health status of general practitioners (GPs) in China, particularly regarding help seeking and self-treatment. The primary aims of this study were to explore GPs' expectations of their own family doctors and their reflection on role positioning, and to explore the objective factors that hinder the system of family doctors. Study design: Cross-sectional study. Methods: We conducted an online survey of Chinese GPs. Descriptive statistics were used to summarize the findings. Results: More than half of the participants (57.20%) reported that their health was normal over the past year. A total of 420 participants (23.35%) reported having chronic diseases. For sleep duration, 1205 participants (66.98%) reported sleeping 6–8 h per day; 473 participants (26.29%) reported chronic insomnia. Two hundred thirty-one participants (12.84%) had possible depression. A total of 595 (33.07%) participants reported that they had contracted a fixed family doctor. In terms of preventing themselves from contracting for a family doctor, the following factors were identified: lack of sufficient time (54.81%), could solve obstacles themselves (50.97%), and embarrassment (24.24%). The proportion of the contract group (12.44%) taking personal relationship as a consideration was higher than that of the non-contract group (7.64%) (χ2 = 10.934 P = 0.01). Most participants (79.90%) in the non-signed group reported never having seen a family doctor. In terms of obstacles, more than half of the signed group thought that they could solve obstacles themselves, while the non-signed group (39.20%) was less confident in the ability of family doctors than the signed group (29.75%) (χ2 = 15.436, P < 0.01). Conclusions: GPs work under great pressure and lack of self-care awareness, resulting in an increased prevalence of health conditions. Most GPs did not have a regular family doctor. Having a family doctor with a fixed contract is more conducive to the scientific management of their health and provides a reasonable solution to health problems. The main factors hindering GPs from choosing a family doctor were time consumption, abilities to solve obstacles themselves, and trust in the abilities of GPs. Therefore, simplifying the process of family doctor visits, Changing the GPs' medical cognition, and strengthening the policy of GP training would be conducive to promoting a family doctor system that enhances hierarchical diagnosis and treatment. International collaboration could integrate GP health support into global healthcare system. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze and explore the nursing effects of integrated medical and nursing care intervention in correction surgery for children with concealed penis. Methods: A total of 76 eligible patients with concealed penis were randomly divided into an observation group and a control group. The control group received conventional nursing care, while the observation group received integrated medical and nursing care intervention. Outcomes include pain levels, comfort status, incidence of complications, and nursing satisfaction were collected and analyzed to investigate the nursing effects of the integrated medical and nursing care model. Results: After 2/3 days of nursing intervention, the patients in the observation group had significantly lower pain scores (measured by FPS-R) compared to the control group (P < 0.05). The patients in the observation group also had significantly higher comfort scores (measured by Kolcabal) compared to the control group (P < 0.05). The incidence of complications in the observation group was significantly lower than that in the control group (2.63 vs. 23.68, P < 0.05). Parental satisfaction in the observation group was significantly higher than that in the control group (P < 0.05). Conclusion: The integrated medical and nursing care intervention in correction surgery for children with concealed penis demonstrated positive nursing effects. It effectively reduced pain, improved comfort, lowered the risk of complications, and increased parental satisfaction. This approach maximizes the role of nursing care and is recommended for clinical implementation. [ABSTRACT FROM AUTHOR]

Background: Mental health issues (depression and suicidal ideation) are increasingly common in children and emerge as escalating public health concerns. The syndemics that underline the importance of risk factor clustering provides a framework for intervention, but there is a lack of research on syndemics involving the adverse interactions of children's mental health problems. This study therefore examined the cumulative and synergistic effects of vulnerable conditions on depression and suicidal ideation among children in China. Methods: A mental health screening census of students in grades 5–12 was conducted from November 2022 to January 2023 in Nanling County, Anhui Province, China. The prevalence and co-occurrence of vulnerable conditions (unfavorable parental marital status, left-behind experience, bullying victimization, and self-harm behavior), depression, and suicidal ideation and the cumulative and synergistic effects of vulnerable conditions on depression and suicidal ideation were explored. Results: Nearly a quarter of students (24.8%) reported at least two syndemic conditions. Overall, the prevalence of depression and suicidal ideation were 20.2% and 24.2% respectively. The odds of depression and suicidal ideation were higher for children with one or more vulnerable conditions and were ten times higher for children with three or more vulnerable conditions compared with those without any vulnerable condition. These four vulnerable conditions can increase the odds of depression and suicidal ideation by interacting synergistically with each other. Conclusion: Our findings signal the importance of addressing mental health syndemics among children in China by simultaneously considering concurrent vulnerable conditions. [ABSTRACT FROM AUTHOR]

Background: It is uncertain if mean platelet volume and periodontitis are related. The objective of this study was to examine the association between levels of mean platelet volume and moderate/severe periodontitis in adult persons who inhabit the U.S. Methods: We screened 6,809 people from the National Health and Nutrition Examination Survey (NHANES 2009–2012). Mean platelet volume was measured in the Mobile Examination Centers (MECs) using the Beckman Coulter analyzer. The category of periodontitis was defined by the CDC/AAP using clinical periodontal parameters. Multiple logistic regression models were employed to examine the distribution for covariate differences across the various independent groups. Four models were employed to examine the relationship between mean platelet volume level and periodontitis. Smoothed curve fitting was utilized to confirm the linearity of the relationships. To determine the impact of factors on the connection between MPV and periodontitis, subgroup analysis and interaction testing were utilized. Results: Results from the multiple logistic regression analysis indicate a significant association between moderate/severe periodontitis and the mean platelet level, even after considering any potential confounding variables (OR = 1.090, 95% CI: 1.019–1.166, P-value = 0.01211). Additionally, those in the upper tertile of mean platelet volume levels had a 21.6% higher probability of developing periodontitis when compared with those in the least tertile of mean platelet levels (OR = 1.216, 95% CI:1.052–1.406, P-value = 0.00816). Moreover, it showed a positive correlation between mean platelet volume (MPV) and moderate/severe periodontitis. Subgroup analyses indicated a positive association between the level of mean platelet volume and moderate/severe periodontitis among individuals who were under 60 years of age, had low income, were obese, never smoked, were heavy drinkers, had hypertension, and had no cardiovascular disease (p < 0.05). However, none of the subgroups exhibited significant interactions (p for interaction > 0.05). Conclusion: A correlation has been found between mean platelet volume levels and periodontal disease in individuals residing in the United States. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare the prevalence of oral frailty among community-dwelling older people in Nanjing, China with the usage of different measurements, and to investigate the potential risk factors of oral frailty. Design: Cross-sectional study. Setting and participants: A total of 338 community-dwelling older people in Nanjing, China were recruited. Methods: Oral frailty was measured based on the Oral Frailty Index-8 (OFI-8) scale and other measurement methods including the number of natural teeth (TN), repetitive saliva-swallowing test (RSST), and oral diadochokinesis (ODK). The chi-square test and the binary logistic regression analysis were performed to identify potential risk factors for oral frailty. Results: There were 310 participants included in the analysis. Prevalence of oral frailty by using the OFI-8, OFI-8 + TN, OFI-8 + ODK, OFI-8 + TN + ODK and RSST measurement methods were 69.0%, 27.4%, 51.9%, 21.0% and 2.9%, respectively. Passive smoking (OR = 2.04; 95%CI 1.03–4.03), being widowed/unmarried (OR1 = 2.53; 95%CI 1.25–5.10; OR2 = 2.94; 95%CI 1.12–7.77), pre-frailty (OR = 1.76; 95%CI 1.03–3.01), frailty (OR = 3.01; 95%CI 1.39–6.54), and aged 80 years and above (OR = 3.99; 95%CI 1.35–11.81) were found to be risk factors of oral frailty by the usage of the four kinds of measurement methods. Conclusions and implications: The definition and diagnostic criteria of oral frailty are strongly needed to be unified in future research. Only subjective assessment is not enough for assessing oral frailty. Among objective indicators, RSST is not suitable as a screening method for oral frailty. In addition, objective indicators including TN and ODK should be valued for early screening and preventive interventions. The risk factors of oral frailty include physical frailty, passive smoking, and being widowed. [ABSTRACT FROM AUTHOR]

Simple Summary: Central nervous system lymphoma (CNSL) is a highly aggressive form of lymphoma. However, treatments such as chemotherapy and radiotherapy may be intolerable for older or specific patients due to the associated toxicity and severe neurotoxicity. Some studies have shown that Bruton tyrosine kinase inhibitors (BTKis) are effective for CNSL. However, most of these studies were small-sample studies, so the efficacy and safety of BTKis in CNSL are not yet clearly defined. Furthermore, the existing reviews have mainly focused on patients with relapsed/refractory CNSL or primary CNSL, and there have been fewer studies on second-generation BTKis, with a lack of reviews on the evidence of BTKis for CNSL. Therefore, this systematic review aims to comprehensively and systematically elucidate the efficacy and safety of BTKis in the treatment of CNSL. The results indicate that BTKis are effective not only for relapsed/refractory cases but also for newly diagnosed CNSL, with an acceptable safety profile. However, high-quality clinical trials are still needed in the future. Background: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Bruton tyrosine kinase inhibitors (BTKis) for central nervous system lymphoma (CNSL). Methods: A systematic review was carried out to identify relevant studies from the PubMed, Embase, Cochrane Library, Web of Science, WanFang, CNKI, and CBM databases. The studies included patients with CNSL who received BTKis and reported the overall response (OR), complete remission (CR), and partial response (PR). An overall effect analysis was performed using STATA 15.0. A random-effects model was utilized to calculate the pooled rates, and 95% confidence intervals (CI) were determined for all outcomes. Results: A total of 21 studies involving 368 patients were included in the meta-analysis. For newly diagnosed CNSL, due to the small simple size, we conducted a quantitative description, and the ORR could reach up to 100%. For relapsed/refractory patients, the pooled ORR was 72% (95% CI: 64–80%, I2 = 54.89%, p = 0.00), with a pooled CR and PR of 43% (95% CI: 33–54%, I2 = 65.40%, p = 0.00) and 23% (95% CI: 13–35%, I2 = 78.05%, p = 0.00), respectively. Most adverse events were hematology-related and generally manageable. Conclusion: BTKis showed acceptable efficacy and safety in treating patients with CNSL. However, large and well-designed trials are still required to confirm BTKis as a treatment for CNSL. [ABSTRACT FROM AUTHOR]

Background: Numerous previous research have established the need for spiritual care among patients with cancer globally. Nevertheless, there was limited research, primarily qualitative, on the spiritual care needs of Chinese inpatients with advanced breast cancer. Furthermore, the need for spiritual care was rarely explored using the Kano model. To better understand the spiritual care needs and attributes characteristics of inpatients with advanced breast cancer, this study examined the Kano model. Methods: A descriptive cross-sectional design study was conducted in the oncology departments of three tertiary grade-A hospitals in China from October 2022 to May 2023. To guarantee high-quality reporting of the study, the Strengthening the Reporting of Observational Studies in Epidemiology Checklist was used. Data on the demographic characteristics questionnaire, the Nurse Spiritual Therapeutics Scale (NSTS), and the Kano model-based Nurse Spiritual Therapeutics Attributes Scale (K-NSTAs) were collected through convenience sampling. The Kano model, descriptive statistics, two independent samples t-tests, and one-way analysis of variance were used to analyze the data. Results: The overall score for spiritual care needs was 31.16 ± 7.85. The two dimensions with the highest average scores, "create a good atmosphere" (3.16 ± 0.95), and the lowest average scores, "help religious practice" (1.72 ± 0.73). The 12 items were distributed as follows: three attractive attributes were located in Reserving Area IV; five one-dimensional attributes were distributed as follows: three one-dimensional attributes were located in Predominance Area I, and two were found in Improving Area II; two must-be attributes were located in Improving Area II; and two indifference attributes were located in Secondary Improving Area III. Conclusion: The Chinese inpatients with advanced breast cancer had a middle level of spiritual care needs, which need to be further improved. Spiritual care needs attributes were defined, sorted, categorized, and optimized accurately and perfectly by the Kano model. And "create a good atmosphere" and "share self-perception" were primarily one-dimensional and must-be attributes. In contrast, the items in the dimensions of "share self-perception" and "help thinking" were principally attractive attributes. Nursing administrators are advised to optimize attractive attributes and transform indifference attributes by consolidating must-be and one-dimensional attributes, which will enable them to take targeted spiritual care measures based on each patient's characteristics and unique personality traits. [ABSTRACT FROM AUTHOR]

Background: Postoperative pain is common in pediatric urological surgery. The study assess the impact of perioperative intravenous infusion of low-dose esketamine on postoperative pain in pediatric urological surgery. Methods: Pediatric patients (n = 80) undergoing urological surgery were randomized into four groups. Patients in the control group were administered an analgesic pump containing only hydromorphone at a dose of 0.1 mg/kg (Hydromorphone Group 1, H1) or 0.15 mg/kg (Hydromorphone Group 2, H2). Patients in the experimental group were injected intravenously with 0.3 mg/kg of esketamine (Esketamine group 1, ES1) or equal volume of saline (Esketamine Group 2, ES2) during anesthesia induction. Esketamine 1.0 mg/kg and hydromorphone 0.1 mg/kg were added to the analgesic pump. Face, Leg, Activity, Crying, and Comfort (FLACC) scale or the Numerical Rating Scale (NRS) and adverse effects were recorded at 2, 6, 24, and 48 h postoperatively. Additionally, total and effective PCA button presses were recorded. Results: In comparison to the H1 group, the pain scores were notably reduced at all postoperative time points in both the ES1 and H2 groups. The ES2 group exhibited lower pain scores only at 24 and 48 h postoperatively. When compared to the H2 group, there were no significant differences in pain scores at various postoperative time points in the ES2 group. However, the ES1 group demonstrated significantly lower pain scores at 6, 24 and 48 h postoperatively, and these scores were also significantly lower than those observed in the ES2 group. The total and effective number of PCA button presses in the ES1, ES2 and H2 group were lower than that in the H1 group (P < 0.001). The incidence of adverse effects within 48 h after surgery was 15% in ES1, 22% in ES2, 58% in H1, and 42% in H2, respectively (P = 0.021). Conclusions: The use of low-dose esketamine infusion in analgesia pump can effectively alleviates postoperative pain in pediatric urological patients, leading to a significant reduction in the number of analgesic pump button press. The combined approach of perioperative anesthesia induction and analgesia pump administration is recommended for optimal pain management in these patients. Trial registration: Chinese Clinical Trial Registry- ChiCTR2300073879 (24/07/2023). [ABSTRACT FROM AUTHOR]

Objective: The main objectives of this study were to identify the active components of Tongguanteng injection (TGT) and investigate the preclinical efficacy and mechanism of TGT on osteosarcoma using a combination of network pharmacology and experimental validation. Methods: To identify the active constituents and targets of TGT against osteosarcoma using network pharmacology, we constructed a network consisting of an 'active ingredient-disease-target-pathway' and a protein–protein interaction (PPI) network. The target organ network was utilized to investigate the distribution of core targets in tissues. Afterwards, the core targets underwent Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The binding energy between receptors and ligands was compared using molecular docking. In addition, SwissADME was employed to forecast the pharmacokinetic characteristics of the substances. Finally, real-time polymerase chain reaction (RT-PCR), cell proliferation assay, morphological analysis, apoptosis assay, mitochondrial membrane potential (MMP) detection, and Western blotting were utilized to confirm the potential mechanisms of TGT treatment in osteosarcoma cell lines 143B and SAOS2. Results: A total of 54 chemical constituents of TGT and 71 targets associated with osteosarcoma were acquired. Through the molecular docking technology, Tenacigenin B, Marsdekoiside, Taraxasterol, Tenacissoside G, Tenacissoside L, and Tenacissoside J were identified as the primary active components of TGT among the various compounds. Analysis of target organs suggests that TGT may play an anti-osteosarcoma role through immune regulation. The GO and KEGG enrichment analysis revealed that TGT could trigger osteosarcoma cell apoptosis by inhibiting the HIF-1 signalling pathway and modulating PD-1 expression and the PD-1 checkpoint pathway in cancer. SwissADME database predicted that Tenacigenin B and Taraxasterol had the best drug-likeness. In vitro studies also demonstrated that TGT suppressed the activity and induced alterations in the morphology of osteosarcoma cells. It decreased MMP levels, triggered apoptosis by increasing Bax expression and Caspase-3 activity, and decreased Bcl-2 expression, thereby exerting an anti-osteosarcoma effect. In the meantime, RT-PCR tests demonstrated that TGT could control immune response against tumors and hinder the proliferation and spread of cancerous cells by impacting the levels of critical factors, including JUN, HSP90AA1, HDAC1, and CDK1. Conclusion: The study accurately anticipated the active components, targets, and pathways of TGT in the management of osteosarcoma. The molecular mechanism of TGT-induced apoptosis in osteosarcoma cells was demonstrated by in vitro experiments. These results provide theoretical and technical support for TGT as a clinical adjuvant drug for osteosarcoma. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to measure pandemic fatigue, physical and mental health, and job status of front‐line medical staff in Ningbo. And to identify factors associated with pandemic fatigue. Background: There was an acute increase in fatigue symptoms at the COVID‐19 pandemic onset. The front‐line medical staff is particularly vulnerable to fatigue due to their high‐intensity work. Design: This was a descriptive, cross‐sectional study conducted using an online survey that included demographic data, investigation of COVID‐19 history and job status. The Fatigue Assessment Scale, GAD‐7 score and Sleep Quality Scale were used to collect data from 479 front‐line medical staff. Methods: The study involved 479 front‐line medical staff in Ningbo, China. The survey was conducted using an online questionnaire that included demographic data, investigation of COVID‐19 history and job status. The Fatigue Assessment Scale, GAD‐7 score and Sleep Quality Scale were used to collect data. Results: The results showed that of the 479 participants, 393 (82%) reported pandemic fatigue, 393 (82%) reported job satisfaction and 433 (90.4%) identified with their sense of job value. Sleep quality, work with a fever, economic subsidies for fighting COVID‐19 and recognizing professional value were significantly correlated with pandemic fatigue. Conclusions: As the COVID‐19 pandemic challenges front‐line medical workers, implementing measures is essential. Health policy implementers could provide sufficient front‐line medical staff to ensure rest in case of infection, promote sleep quality and foster professional value and financial subsidies in units. Relevance to clinical practice: The study shows how pandemic fatigue affects front‐line medical staff during the COVID‐19 pandemic and suggests measures to support them, including promoting sleep quality, providing rest for infected staff, fostering professional value and financial subsidies. The recommendations are relevant to clinical practice as they help support medical staff and ensure high‐quality care for patients during the pandemic. Patient or Public Contribution: No Patient or Public Contribution. Not applicable. [ABSTRACT FROM AUTHOR]

Objective. To investigate the relationship between glucagon-like peptide-1 receptor gene polymorphisms and susceptibility to early onset type 2 diabetes. Methods. Samples from 316 type 2 diabetes patients with early onset type 2 diabetes (n = 137) and late-onset type 2 diabetes (n = 179) and 145 nondiabetic individuals were analyzed. Multiplex PCR combined with resequencing Hi-Reseq technology was used to detect single nucleotide polymorphisms of the glucagon-like peptide-1 receptor gene, and the allele frequency, genotype distribution, and clinical parameters were analyzed between each diabetes subgroup and the control group. Results. Sixteen single nucleotide polymorphisms were identified in the exonic region of the glucagon-like peptide-1 receptor gene according to the minor allele frequency (MAF > 0.05) in the participants. Among these, the glucagon-like peptide-1 receptor rs3765467 (G⟶A) mutation was statistically associated with early onset type 2 diabetes. Compared with that of the GG carriers, carriers of genotype AA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. In the dominant model, the frequencies of the rs3765467 AA + GA genotype were significantly decreased in the early onset type 2 diabetes group, and carriers of genotype AA + GA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. Moreover, fasting C peptide levels were significantly higher in GA + AA genotype carriers than those in GG genotype carriers. Conclusion. The glucagon-like peptide 1 receptor rs3765467 polymorphism was significantly associated with age at type 2 diabetes diagnosis and thus may be used as a marker to screen and detect individuals at risk of developing early onset type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Effective pain management is closely related to nurses' knowledge, attitudes and empathy regarding pain. Nursing educators and managers should understand the relationship between nurses' pain management knowledge, attitudes and empathy level, and take targeted measures accordingly. Currently, there is limited study exploring the relationship between pain empathy and pain knowledge and attitudes among nurses in North China. Objectives: The purpose of this study was to investigate the level of nurses' pain management knowledge and attitudes and pain empathy, to analyze the factors influencing pain empathy, and to explore the relationship between these two variables. Design: This study was a quantitative, descriptive-correlation design. Setting and participants: The study population was registered nurses in North China, the sample included 177 registered nurses in North China. Methods: Data were collected with the "General data questionnaire", "Knowledge and attitudes survey regarding pain" (KASRP) and the "Empathy for pain scale" (EPS) via Wechat mini program "Questionnaire Star". Results: The 177 registered nurses completed the survey. The averege correct rate for KASRP was (51.94 ± 9.44)%, and none of the respondents achieved a percentage score of >80%. The mean score for pain empathy was (2.78 ± 0.78), the empathy reactions dimension was (2.99 ± 0.77), and the body and mind discomfort dimension was (2.71 ± 0.80). The results of multiple stepwise linear regression showed that whether they had received empathy training, whether they had greater trauma or severe pain and whether they had negative emotions were independent influencing factors for EPS scores. Pearson correlation analysis showed that KASRP scores were positively correlated with EPS scores (r = 0.242, P < 0.05). Conclusions: The pain knowledge and attitudes of nurses in North China are far from optimal. Nurses have a relatively low accuracy rate in areas such as medication knowledge, assessment of patient pain based on case studies, and handling PRN prescriptions. Nursing educators and administrators need to design some pain management courses in a targeted manner. Nurses' empathy for pain was at a moderate level. Pain empathy was positively correlated with pain knowledge and attitudes, suggesting that empathy for pain can be developed postnatally. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the relationship between activities of daily living (ADL) limitations and family doctor contract services among overweight and obese older adults, as well as to examine whether this association varies by urban-rural residence. Methods: Data for the present study were obtained from the sixth Health Service of Shandong province, China. A total of 4,249 overweight and obese older adults were included in this study. Binary logistic regression models were used to evaluate the relationship between ADL limitations and family doctor contract services, to examine the potential differences between urban and rural areas. Results: Of 4,249 overweight and obese older adults, the prevalence of limitations in ADL and family doctor service contracting rate in Shandong province were 12.47% and 66.46%, respectively. The results of the regression analyses revealed that overweight and obese older adults with ADL limitations were more likely to sign up for family doctor services than those without ADL limitations (OR = 1.27, 95%CI: 1.02–1.58, P = 0.033). Only among rural overweight and obese older adults, the relationship between ADL limitations and family doctor contract services was statistically significant (OR = 1.50, 95%CI: 1.13–1.99, P = 0.005). Conclusions: Our study found a significant association between ADL limitations and family doctor contract services among overweight and obese older adults in Shandong, China. This relationship differed by urban-rural residence. To promote the positive development of the family doctor contract service system, the government should increase publicity, provide personalized contracted services, and prioritize the healthcare needs of overweight and obese older adults with ADL limitations, with special attention to rural areas. [ABSTRACT FROM AUTHOR]

Background: The anatomical characteristics of difficult airways can be analysed geometrically. This study aims to develop and validate a geometry-assisted difficult airway screening method (GADAS method) for difficult tracheal intubation. Methods: In the GADAS method, a geometric simulated model was established based on computer graphics. According to the law of deformation of the upper airway on laryngoscopy, the expected visibility of the glottis was calculated to simulate the real visibility on laryngoscopy. Validation of the new method: Approved by the Ethics Committee of Yijishan Hospital of Wannan Medical College. Adult patients who needed tracheal intubation under general anaesthesia for elective surgery were enrolled. The data of patients were input into the computer software to calculate the expected visibility of the glottis. The results of tracheal intubation were recorded by anaesthesiologists. The primary observation outcome was the screening performance of the expected visibility of the glottis for difficult tracheal intubation. Results: The geometric model and software of the GADAS method were successfully developed and are available for use. We successfully observed 2068 patients, of whom 56 patients had difficult intubation. The area under the receiver operating characteristic curve of low expected glottis visibility for predicting difficult laryngoscopy was 0.96 (95% confidence interval [CI]: 0.95–0.96). The sensitivity and specificity were 89.3% (95% CI: 78.1-96.0%) and 94.3% (95% CI: 93.2%-95.3), respectively. Conclusions: It is feasible to screen difficult-airway patients by applying computer techniques to simulate geometric changes in the upper airway. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the research status and hotspots of surgical treatment for tremor in Parkinson's disease (PD) from 2002 to 2022, utilizing bibliometric and visual analysis. Additionally, it aims to offer insights into future research trends in this field. Methods: This study collected publications on the surgical treatment of tremor in PD from 2002 to 2022 using the Web of Science (WOS) database. CiteSpace, VOSviewer, and Scimago Graphica were employed to quantify the number of publications and analyze the bibliographic information networks, including the contributions of countries/cities, authors, keywords, and co-cited references. Results: A total of 2,815 publications were included in the study, revealing that 541 scientific institutions experienced an increase in publications from 2002 to 2022. Michael Okun emerged as the most productive author, and the United States emerged as the leading hub for research. The study identified 772 keywords. Noteworthy citation bursts and long-term activity were observed in pallidotomy, bilateral stimulation, and focused ultrasound thalamotomy. The top 10 highly co-cited references comprised eight deep brain stimulation (DBS) studies (including two follow-up studies and six randomized controlled trials), one randomized controlled trial on focused ultrasound, and one consensus on tremor. Conclusion: This study uses an in-depth and systematic bibliometric and visualization analysis to visualize the evolution of research and identify emerging hotspots. The identified hotspots are as follows: Firstly, DBS has received significant attention and widespread recognition as a surgical treatment for tremor in PD. Secondly, there are various key aspects to consider in DBS, such as operative indications, operative targets, and surgical protocols. Lastly, magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as a promising treatment option in the surgical management of tremor in Parkinson's disease. This research also provides insights into the phenomenon of these hotspots, offering valuable prompts and reminders for further research. [ABSTRACT FROM AUTHOR]

Segmentation is a crucial step in extracting the medical image features for clinical diagnosis. Though multiple metrics have been proposed to evaluate the segmentation performance, there is no clear study on how or to what extent the segmentation errors will affect the diagnostic related features used in clinical practice. Therefore, we proposed a segmentation robustness plot (SRP) to build the link between segmentation errors and clinical acceptance, where relative area under the curve (R-AUC) was designed to help clinicians to identify the robust diagnostic related image features. In experiments, we first selected representative radiological series from time series (cardiac first-pass perfusion) and spatial series (T2 weighted images on brain tumors) of magnetic resonance images, respectively. Then, dice similarity coefficient (DSC) and Hausdorff distance (HD), as the widely used evaluation metrics, were used to systematically control the degree of the segmentation errors. Finally, the differences between diagnostic related image features extracted from the ground truth and the derived segmentation were analyzed, using the statistical method large sample size T-test to calculate the corresponding p values. The results are denoted in the SRP, where the x-axis indicates the segmentation performance using the aforementioned evaluation metric, and the y-axis shows the severity of the corresponding feature changes, which are expressed in either the p values for a single case or the proportion of patients without significant change. The experimental results in SRP show that when DSC is above 0.95 and HD is below 3 mm, the segmentation errors will not change the features significantly in most cases. However, when segmentation gets worse, additional metrics are required for further analysis. In this way, the proposed SRP indicates the impact of the segmentation errors on the severity of the corresponding feature changes. By using SRP, one could easily define the acceptable segmentation errors in a challenge. Additionally, the R-AUC calculated from SRP provides an objective reference to help the selection of reliable features in image analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: Given the variable aggressiveness of PCa, patients with indolent PCa do not require intervention, but rather require active surveillance and close lifelong follow-up, while those with invasive PCa require surgery, various types of radiation therapy, androgen-deprivation therapy (ADT), or multimodal treatment. Hence, it is critical to accurately distinguish indolent from invasive PCa for prognosis evaluation and treatment decision-making. The aim of the present study was to investigate the value of MR radiomics feature-based machine learning (ML) models in predicting the Ki67 index and Gleason grade group (GGG) of PCa. Biparametric magnetic resonance imaging (bpMRI) radiomics-based ML models to predict immuno-histochemically-determined Ki67 expression and the GGG demonstrated the ability to identify aggressive PCa. A preliminary exploration was performed in the conjoint analysis, laying the theoretical foundation for models predicting two or more variables; such models are expected to provide more comprehensive pathological information and provide valuable guidance for clinical decision-making in a noninvasive, synchronous, and objective manner. Purpose: The Ki67 index and the Gleason grade group (GGG) are vital prognostic indicators of prostate cancer (PCa). This study investigated the value of biparametric magnetic resonance imaging (bpMRI) radiomics feature-based machine learning (ML) models in predicting the Ki67 index and GGG of PCa. Methods: A total of 122 patients with pathologically proven PCa who had undergone preoperative MRI were retrospectively included. Radiomics features were extracted from T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) maps. Then, recursive feature elimination (RFE) was applied to remove redundant features. ML models for predicting Ki67 expression and GGG were constructed based on bpMRI and different algorithms, including logistic regression (LR), support vector machine (SVM), random forest (RF), and K-nearest neighbor (KNN). The performances of different models were evaluated with receiver operating characteristic (ROC) analysis. In addition, a joint analysis of Ki67 expression and GGG was performed by assessing their Spearman correlation and calculating the diagnostic accuracy for both indices. Results: The ML model based on LR and ADC + T2 (LR_ADC + T2, AUC = 0.8882) performed best in predicting Ki67 expression, and ADC_wavelet-LHH_firstorder_Maximum had the highest feature weighting. The SVM_DWI + T2 (AUC = 0.9248) performed best in predicting GGG, and DWI_wavelet HLL_glcm_SumAverage had the highest feature weighting. The Ki67 and GGG exhibited a weak positive correlation (r = 0.382, p < 0.001), and LR_ADC + DWI had the highest diagnostic accuracy in predicting both (0.6230). Conclusion: The proposed ML models are suitable for predicting both Ki67 expression and GGG in PCa. This algorithm could be used to identify indolent or invasive PCa with a noninvasive, repeatable, and accurate diagnostic method. [ABSTRACT FROM AUTHOR]

Tamoxifen is a drug used for treating breast cancer (BC), especially for individuals diagnosed with estrogen receptor-positive (ER+) BC. Its prolonged use could reduce the risk of recurrence and significantly lengthen the survival rate of BC patients. However, an increasing number of patients developed resistance to tamoxifen treatment, which reduced therapeutic efficiency and caused substandard prognosis. Therefore, the exploration of the molecular processes involved in tamoxifen resistance (TR) is urgently required. This investigation aimed to elucidate the relationship of microRNA-330 (miR-330-3p) with the TR of BC. There is little information on miR-330-3p′s link with drug-resistant BC, although it is well known to regulate cell proliferation and apoptosis. Primarily, miR-330-3p expression in parental BC (MCF7/T47D), TR (MCF7-TR), and T47D/TR cell lines was detected by qRT-PCR. Then, the impact of miR-330-3p on the TR of BC cells was assessed by a cell proliferation assay. Lastly, dual-luciferase reporter, qRT-PCR, and western blot assessments were carried out to identify histone deacetylase 4 (HDAC4) as the potential miR-330-3p target gene. The data indicated that miRNA-330 was overexpressed in TR ER+ BC cells and its overexpression could induce TR. Furthermore, miRNA-330 could also reduce the expression of HDAC4, which is closely linked to TR, and overexpression of HDAC4 could reverse miRNA-330-induced drug resistance. In summary, miR-330-3p could induce TR of ER+ BC cells by downregulating HDAC4 expression, which might be a novel marker of TR and a possible treatment target against BC patients who are tamoxifen-resistant. [ABSTRACT FROM AUTHOR]

Background: Temporomandibular joint disorders (TMD) is the most common non-dental pain complaint in the maxillofacial region, which presents a variety of symptoms and signs, including temporomandibular joints (TMJ) and masticatory muscle pain, joint noise, tinnitus, headaches, irregular or restricted mandibular function, masticatory difficulty, and restricted mouth opening. When comes to the relationship between obesity and TMD, it has remained controversial and inconsistent, therefore, we first conducted this meta-analysis to estimate the unclear relationship between obesity and TMD. Methods: Searches were conducted in PubMed, Web of Science, Embase, and Cochrane Library. Subjects were divided into five groups according to BMI level in this study, including the normal weight group: 18.5 ≤ BMI < 25, overweight group: 25 ≤ BMI < 30, obesity group: BMI ≥ 30, control group: BMI < 25, and overweight and obesity group: BMI ≥ 25. Statistics analyses were conducted using Stata (15.0). The number of PROSPERO was CRD42022368315. Results: Eight studies were included in this study, and six articles with a total of 74,056 participants were synthesized for meta-analysis. Compared to normal weight individuals, overweight and obesity together decreased the risk of TMD (OR = 0.66, 95% CI = 0.46–0.95), and it was significantly decreased by obesity alone (OR = 0.58). Moreover, it was lower in obesity compared with control subjects (OR = 0.83, 95% CI = 0.73–0.94). Furthermore, in overweight and obese individuals, it was much lower in obesity than in overweight (OR = 0.82, 95% CI = 0.71–0.94). Conclusions: Obesity is not a risk factor for TMD, and maybe a protective factor for TMD, of which patients with larger BMI are less likely to suffer from TMD pain. Therefore, the value of BMI should be taken into consideration in the assessment of TMD. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a prevalent condition characterized by low bone density and increased risk of fractures, resulting in a significant healthcare burden. Previous research has suggested that serum ferritin levels may be related to the risk of developing osteoporosis. The aim of this study was to investigate the relationship between dietary iron intake and the development of osteoporosis. Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018, a total of 11,690 adults aged over 20 were evaluated. Bone mineral density (BMD) measurements of the femoral neck and lumbar spine were used to assess osteoporosis and osteopenia. Dietary iron intake was determined using food intake interviews and the Food and Nutrient Database for Dietary Studies. Logistic regression models were applied to investigate the association between dietary iron consumption and osteopenia and osteoporosis. Results: After adjusting for sociodemographic factors, compared with those who had the first quartile (Q1) of dietary iron intake, the odds ratio (OR) for osteopenia across the quartiles of dietary iron intake levels was 0.88 (95%CI: 0.79–0.98), 0.80 (95%CI: 0.72–0.89), and 0.74 (95%CI: 0.67–0.83) for Q2, Q3, and Q4, respectively. And the OR for osteoporosis across the quartiles of dietary iron intake levels was 1.00, 0.77 (95%CI: 0.50–1.19), 0.54 (95%CI: 0.34–0.89), and 0.83 (95%CI: 0.54–1.29) for Q1, Q2, Q3, and Q4, respectively. Notably, the observed association was significant among females but not males. Conclusion: The risk of osteopenia/osteoporosis in females decreases with a moderate increase in dietary iron consumption. For females to preserve bone health, moderately increasing their dietary iron intake without overindulging should be seen as a key approach. Our study provides useful insights for developing dietary strategies to prevent and manage osteoporosis in vulnerable populations. [ABSTRACT FROM AUTHOR]

Aim: To determine the associated factors of professional identity among intensive care unit (ICU) nurses during the COVID‐19 pandemic in China. Design: Multicentre cross‐sectional study. Methods: This study invited 348 ICU nurses in five hospitals in China from May to July 2020. Online self‐report questionnaires were adopted to collect their demographic and occupational characteristics, perceived professional benefits and professional identity. Based on univariate and multiple linear regression analysis, a path analysis was performed to determine the associated factors' effects on professional identity. Results: The mean score of professional identity was 102.38 ± 16.46. Perceived professional benefits, doctor recognition level and family support level were associated with ICU nurses' professional identity. The path analysis revealed that perceived professional benefits and doctor recognition level had direct effects on professional identity. In addition, doctor recognition level and family support level had indirect effects on professional identity through the mediation of perceived professional benefits. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is highly malignant and associated with poor prognoses in patients worldwide. There has been widespread recognition that lncRNAs are tightly linked to LUAD tumorigenesis and development. Here, we identified that the LINC00621 level was increased in LUAD tissues and concerned with the poor prognoses in LUAD patients. Methods: Bioinformatical analysis and RT‐qPCR determined the level of LINC00621 in LUAD tissues and cell lines. The admeasurement of the proliferation, migration, and invasion abilities of LUAD cells was utilized in the CCK8 and Transwell formulas. Luciferase reporter assay was used to corroborate the downstream target genes of LINC00621. The phosphorylated SMAD3 protein was tested by Western blotting assay. The impression of LINC00621 knockdown on LUAD tumor growth and metastasis put into effect by murine models. ChIP‐qPCR assay was carried out to verify the transcriptional regulation by FOXA1 on LINC00621. Results: In vitro, the knockdown of LINC00621 significantly reduced the proliferative, migrating, and invasive abilities, the same was true for tumorigenesis and metastasis in vivo. MiR‐34a‐5p as a straight target of LINC00621 was ascertained, and LUAD patients with inferior miR‐34a‐5p levels had undesirable prognoses. Furthermore, TGFBR1 is an immediate and functional connection site of miR‐34a‐5p. Collectively, LINC00621 can sponge miR‐34a‐5p and upregulate TGFBR1 levels, which further sensitized TGF‐β signaling pathway. Finally, it was revealed that FOXA1 transcriptionally upregulated LINC00621. Conclusion: This study uncovered that FOXA1‐induced LINC00621 promotes LUAD progression via the miR‐34a‐5p/TGFBR1/TGF‐β axis, and is one novel therapeutic target that may be used in LUAD treatment. [ABSTRACT FROM AUTHOR]

Background: Management of postoperative pulmonary complications (PPCs) can be challenging in gastric cancer patients undergoing radical gastrectomy and is always associated with poor prognosis. Even though oncology nurse navigator (ONN) provide effective and critical individualized care to patients, little is known about their impact on the occurrence of PPCs in gastric cancer patients. This study aimed to determine whether ONN decreases the incidence of PPCs in gastric cancer patients. Methods: This was a retrospective review in which data for gastric cancer patients at one centre was evaluated before and after an ONN hired. An ONN was introduced to patients at their initial visit to manage pulmonary complications throughout treatment. The research was conducted from 1 August 2020 to 31 January 2022. The study participants were divided into the non-ONN group (from 1 August 2020 to 31 January 2021) and the ONN group (from 1 August 2021 to 31 January 2022). The incidence and severity of PPCs between the groups were then compared. Results: ONN significantly decreased the incidence of PPCs (15.0% vs. 9.8%) (OR = 2.532(95% CI: 1.087–3.378, P = 0.045)), but there was no significant difference in the components of PPCs including pleural effusion, atelectasis, respiratory infection, and pneumothorax. The severity of PPCs was also significantly higher in the non-ONN group (p = 0.020). No significant statistical difference was observed for the major pulmonary complications ( 3) between the two groups (p = 0.286). Conclusions: Role of ONN significantly decrease the incidence of PPCs in gastric cancer patients undergoing radical gastrectomy. [ABSTRACT FROM AUTHOR]

Background: Patients treated in the intensive care unit (ICU) may experience a reversal of day and night. The circadian rhythm in ICU patients can be disturbed. Methods: To explore the relationship between ICU delirium and the circadian rhythms of melatonin, cortisol and sleep. A prospective cohort study was carried out in a surgical ICU of a tertiary teaching hospital. Patients who were conscious during the ICU stay after surgery and were scheduled to stay in the ICU for more than 24 h were enrolled. Serum melatonin and plasma cortisol levels were measured three times a day by drawing arterial blood on the first three days after ICU admission. Daily sleep quality was assessed by the Richard-Campbell Sleep Questionnaire (RCSQ). The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) was performed twice a day to screen for ICU delirium. Results: A total of 76 patients were included in this study, and 17 patients developed delirium during their ICU stay. Melatonin levels were different at 8:00 (p = 0.048) on day 1, at 3:00 (p = 0.002) and at 8:00 (p = 0.009) on day 2, and at all three time points on day 3 (p = 0.032, 0.014, 0.047) between delirium and non-delirium patients. The plasma cortisol level in the delirium patients was significantly lower than that in the non-delirium patients at 16:00 on day 1 (p = 0.025). The changes in melatonin and cortisol secretion levels exhibited obvious biological rhythmicity in non-delirium patients (p < 0.001 for melatonin, p = 0.026 for cortisol), while no rhythmicity was found in melatonin and cortisol secretion levels in the delirium group (p = 0.064 for melatonin, p = 0.454 for cortisol). There was no significant difference in RCSQ scores in the first three days between the two groups. Conclusions: The disturbance of the circadian rhythm of melatonin and cortisol secretion was associated with the development of delirium in ICU patients. Clinical staff should pay more attention to the importance of maintaining patients' normal circadian rhythms in the ICU. Trial registration: The study was registered with the US National Institutes of Health ClinicalTrials.gov(NCT05342987) (25/04/2022). [ABSTRACT FROM AUTHOR]

Simple Summary: Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming a major cause of cirrhosis and hepatocellular carcinoma (HCC). The risk of liver-related mortality, including HCC, significantly increases with the progression of liver fibrosis in NAFLD patients. This study aimed to characterize the molecular and cellular changes occurring during liver fibrosis progression in NAFLD patients. The identified gene and immune cell signatures may lead to novel surveillance and prevention strategies. The expression of immune- and cancer-related genes was measured in liver biopsies from 107 NAFLD patients. The strongest difference in overall gene expression was between liver fibrosis stages F3 and F4, with 162 cirrhosis-associated genes identified. Strong correlations with fibrosis progression from F1 to F4 were observed for 91 genes, including CCL21, CCL2, CXCL6, and CCL19. In addition, the expression of 21 genes was associated with fast progression to F3/F4 in an independent group of eight NAFLD patients. These included the four chemokines, SPP1, HAMP, CXCL2, and IL-8. A six-gene signature including SOX9, THY-1, and CD3D had the highest performance detecting the progressors among F1/F2 NAFLD patients. We also characterized immune cell changes using multiplex immunofluorescence platforms. Fibrotic areas were strongly enriched in CD3+ T cells compared to CD68+ macrophages. While the number of CD68+ macrophages increased with fibrosis severity, the increase in CD3+ T-cell density was more substantial and progressive from F1 to F4. The strongest correlation with fibrosis progression was observed for CD3+CD45R0+ memory T cells, while the most significant increase in density between F1/F2 and F3/F4 was for CD3+CD45RO+FOXP3+CD8− and CD3+CD45RO−FOXP3+CD8− regulatory T cells. A specific increase in the density of CD68+CD11b+ Kupffer cells with liver fibrosis progression was also observed. [ABSTRACT FROM AUTHOR]

Background: Caregivers of asthmatic children have a poor knowledge of proper asthma-management practices in Nigeria. This study examined the knowledge, attitudes, and practice behaviors of caregivers in the management of asthma in children under 5 years of age in Oyo State, Nigeria. Methods: While a mixed method was used in the original research, this brief describes the quantitative method used in this study to evaluate caregivers' asthma-management practices. A 55-item questionnaire on childhood asthma knowledge, attitude, and practice was administered during child welfare-clinic visits to 118 caregivers. Data were analyzed using the IBM SPSS Version 25.0. Statistical significance was set at p < 0.05 and 95% CI. Result: More than 70% of caregivers knew that asthma is associated with airway inflammation and about 90% knew that flu infections triggered asthma attacks in their children. Caregivers with a higher income (OR = 3.0; 95% CI = 1.558–5.778; p = 0.001) were 3.0 times more likely to practice proper asthma-care behavior than those with a lesser income. Conclusions: Childhood asthma remains underdiagnosed and undertreated in Nigeria. An optimal public health approach is needed to identify and target underserved communities that suffer poorer asthma outcomes and to improve caregivers' knowledge and practices of asthma management. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the epidemiological pattern of maxillofacial fractures in northwestern China by retrospectively analysing the demographics, aetiologies, concomitant injuries, fracture sites, and management. Methods: A 10-year retrospective analysis of 2240 patients with maxillofacial fractures admitted to the General Hospital of Ningxia Medical University was conducted. The extracted data included sex, age, aetiology, fracture site, concomitant injuries, time of treatment, therapeutic approaches and complications. Statistical analyses were performed, including descriptive analysis and the chi-square test. Logistic regression was used to determine the impact factors of maxillofacial fractures and concomitant injuries. P values < 0.05 were considered statistically significant. Results: The age of the included patients ranged from 1 to 85 years, and the mean age was 35.88 ± 15.69 years. The male-to-female ratio was 3.9:1. The most frequent aetiology of maxillofacial fractures was road traffic accidents (RTAs) (56.3%), and the most common fracture sites were the anterior wall of the maxillary sinus, arcus zygomaticus and mandibular body. A total of 1147 patients (51.2%) were affected by concomitant injuries, with craniocerebral injury being the most common. Logistic regression analyses revealed increased risks of mid-facial fractures in elderly individuals (odds ratio (OR) = 1.029, P < 0.001) and females (OR = 0.719, P = 0.005). Younger patients had a higher risk of mandibular fractures (OR = 0.973, P < 0.001). RTAs increased the risk for mid-facial fractures and high falls increased the risk for mandibular fractures. Conclusions: The maxillofacial fracture pattern is correlated with sex, age and aetiology. Patients were mainly young and middle-aged males, and the main cause of injury was RTAs, mostly causing compound fractures. Medical staff must be systematically educated to comprehensively examine patients with injuries resulting from RTAs. The management of patients with fractures requires thorough consideration of the patient's age, aetiology, fracture site, and concomitant injuries. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection, for which effective therapeutic strategies are still absent. Shengjiang San (SJS), a well-known Traditional Chinese Medicine formula, has been widely used clinically. However, its role in sepsis-induced lung injury remains unclear. Methods: To explore its specific mechanism, we firstly established a sepsis animal model using cecal ligation and puncture (CLP) and treated MH-S cells with LPS plus ATP. Then, UPLC/Q-TOF–MS/MS was utilized to identify its active ingredients. Network pharmacology analysis was performed to uncover the potential mechanism. HE staining and biochemical analysis were conducted to validate its therapeutic effect. ELISA was applied to detect the release of pro-inflammatory and anti-inflammatory cytokines. Western blot was utilized to detect the protein levels of GSDMD, NLRP3, P65, ASC and caspase-1. Results: SJS could dramatically increase the survival rate of sepsis. In addition, it is able to inhibit the pro-inflammatory cytokines release at day 1 post CLP while promote their production at day 7, indicating SJS could attenuate uncontrolled inflammatory response in the early stage and improve immunosuppression in the late phase. Network pharmacology analysis showed that pyroptosis is the crucial action SJS exerted in the protection of sepsis-induced lung injury. Western blot data implicated SJS could attenuate pyroptosis in early sepsis while enhance in the late phase. Conclusions: SJS acted to alleviate sepsis-induced lung injury through its bidirectional regulatory effect. [ABSTRACT FROM AUTHOR]

Introduction: The misfolding and aggregation of ß-amyloid (Aß) easily form Aß fibers, which are continuously deposited in the brain, leading to the massive generation of amyloid plaques, severely destroying neuronal connections, and promoting Alzheimer's disease (AD) The occurrence and development of AD is one of the pathogenesis of AD. There is an urgent need to develop inhibitors against Aß aggregation, which is hopefully a potential way to treat AD. Methods: In this study, we first found the crystal structure of the Aβ1-42 receptor protein from the RCSB PDB protein structure database and used the SYBYL X2.0 software for molecular docking, and then used the Peptide Ranker, Innovagen, DPL, and ToxinPred online websites to perform peptides. Predict the activity score, toxicity and water solubility, and then calculate the affinity constant KD value of polypeptide and Aβ through Surface Plasmon Resonance (SPR) experiment. Subsequently, the CCK-8 kit method was used to determine the toxicity of different concentrations of peptides (3.125, 6.25, 12.5, 25, 50, 100, 200 μM) to PC12 cells, and then the peptides and Aβ according to different concentration ratios (1:4, 1:2, 1:1, 1:0.5, 1:0.25, 0:4), this method is also used to detect the effect of peptides on Aβ-induced neurotoxicity. The thioflavin T (ThT) fluorescence method was used to detect the effects of peptides (50 μM) on Aβ (25 μM) aggregation inhibitory effect. Results: The results showed that the CScore of YVRHLKYVRHLK peptide molecule docking was 10.0608, the predicted activity score was 0.20, and the KD value was 5.385 × 10-5. The ThT and CCK-8 kit method found that the peptide itself is less toxic to PC12 cells at a concentration of 50 μM, and it has a significant inhibitory effect on the formation of Aβ1-42 aggregates when incubated with Aβ1-42 at a ratio of 1:1 (p < 0.05) and can significantly reduce the PC12 cytotoxicity induced by Aβ1-42 (p < 0.05). Conclusion: In conclusion, the polypeptide YVRHLKYVRHLK designed in this study has a neuroprotective effect on PC12 cytotoxicity induced by Aβ1-42. [ABSTRACT FROM AUTHOR]

Aim: This study aims to evaluate demands for general and pharmacological knowledge and training related to intravenous (IV) therapy among pediatric nurses. Materials and Methods: This multicentric cross-sectional study involved 12,707 pediatric nurses from 100 hospitals in China. A questionnaire was used to assess information about IV drug administration training received, and the demands for pharmacology-related knowledge, and corresponding methods of acquisition. A generalized linear model using Logit link function was employed to assess relationships between factors and multivariate analysis was conducted. Results: More than 99% of participants showed their training demands for IV therapy training. Pediatric nurses' demands and methods for acquiring IV therapy knowledge and the knowledge related to IV therapy pharmacology have significant differences in social demographic factors, previous knowledge, whether they have received training or not, and other factors (all P < 0.05). Received a needlestick injury in the past month (P = 0.007) and knowledge acquired through in-hospital or out-of-hospital training (P = 0.039) were factors that reduced the demands for methods to acquire further pharmacology-related knowledge of IV therapy. Working in internal medicine (P = 0.025) and not having experienced a needlestick injury in the past year (P = 0.007) reduced the demands for IV therapy knowledge. Attended hospital (P = 0.007) or departmental meetings (P = 0.009), being pediatric primary nurses (P = 0.044), and studied special IV guidelines (P = 0.006) reduced the desire for methods to acquire IV therapy knowledge. Conclusion: There was a high demand for greater general and pharmacological knowledge related to IV therapy among pediatric nurses. Resources should be coordinated to provide ongoing training to nurses to improve the quality of IV care. [ABSTRACT FROM AUTHOR]

Purpose: Various physiological and psychological negative situations experienced by nurses as a result of COVID-19 pandemic have been shown to increase their perception of organizational difficulty and decrease their career commitment, thereby accelerating the turnover rate of nurses. Resilience and career adaptability have important influences on career commitment, so there is a need to evaluate the relationships between them and the underlying mechanisms. Patients and methods: Using a cross-lagged design, the Career Adaptability Scale, the Chinese version of career commitment, and Davidson's Resilience Scale as research methods, we studied 692 nursing students for two consecutive years to evaluate the relationship among career adaptability, resilience, and career commitment. Results: Career adaptability at T1 substantially and positively predicts the career commitment at T2. Career adaptability and resilience are mutually predictive. No interaction is found between resilience and career commitment over time. There is a substantial difference in the cross-lagged relationship among career adaptability, resilience, and career commitment for low- and high-career interest. Conclusion: Our results show the importance of developing career commitment early on. Developing career adaptability, enhancing resilience, and increasing career interest in nursing students might help to increase career commitment. [ABSTRACT FROM AUTHOR]

Simple Summary: Approximately 70% of patients with advanced epithelial ovarian cancer who achieve clinical remission after initial surgery and chemotherapy have a recurrence. Wilms' Tumor 1 (WT1), which is overexpressed in ovarian cancer cells, is a promising target for tumor-directed immunotherapy for ovarian cancer due to its prevalence and specificity. The aim of our open-label, non-randomized phase I study was to assess the safety of a WT1 peptide vaccine (galinpepimut-S) in combination with nivolumab in patients with WT1-expressing ovarian cancer in second or third remission. In a sample of 11 patients, the combination of galinpepimut-S vaccine and nivolumab induced immune responses and was deemed safe and tolerable. Our findings provide additional evidence that the combination of immune checkpoint inhibitors (e.g., nivolumab) and vaccines results in enhanced anti-tumor immune responses. We examined the safety and immunogenicity of sequential administration of a tetravalent, non-HLA (human leukocyte antigen) restricted, heteroclitic Wilms' Tumor 1 (WT1) peptide vaccine (galinpepimut-S) with anti–PD-1 (programmed cell death protein 1) nivolumab. This open-label, non-randomized phase I study enrolled patients with WT1-expressing ovarian cancer in second or third remission from June 2016 to July 2017. Therapy included six (every two weeks) subcutaneous inoculations of galinpepimut-S vaccine adjuvanted with Montanide, low-dose subcutaneous sargramostim at the injection site, with intravenous nivolumab over 12 weeks, and up to six additional doses until disease progression or toxicity. One-year progression-free survival (PFS) was correlated to T-cell responses and WT1-specific immunoglobulin (Ig)G levels. Eleven patients were enrolled; seven experienced a grade 1 adverse event, and one experienced a grade ≥3 adverse event considered a dose-limiting toxicity. Ten (91%) of eleven patients had T-cell responses to WT1 peptides. Seven (88%) of eight evaluable patients had IgG against WT1 antigen and full-length protein. In evaluable patients who received >2 treatments of galinpepimut-S and nivolumab, the 1-year PFS rate was 70%. Coadministration of galinpepimut-S and nivolumab demonstrated a tolerable toxicity profile and induced immune responses, as indicated by immunophenotyping and WT1-specific IgG production. Exploratory analysis for efficacy yielded a promising 1-year PFS rate. [ABSTRACT FROM AUTHOR]

Background: Frailty has been considered to be associated with major mortality and increased length of stay after cardiac surgery. This study aimed to explore the predictive potential of frailty assessment in the prognosis of elderly patients undergoing bypass surgery. Methods: This study assessed the preoperative frailty according to the Fried's frailty phenotype, and included 150 frail and 150 non-frail elderly patients (≥ 65 y) who underwent bypass surgery. The present study evaluated the prognosis of elderly patients based on sequential organ failure assessment (SOFA) score, and collected clinical indicators to construct logistic regression models with the prognosis as the dependent variable, to explore the potential predictive ability of preoperative frailty. Moreover, this study focused on the complications and analyzed the relationship between preoperative frailty and postoperative complications. Results: In the present study, 244 patients were divided into the favorable prognosis group and 56 patients were divided into the unfavorable prognosis group. Logistic regression analysis showed that increased myoglobin and high cardiac function classification were independent risk factors for unfavorable prognosis in elderly patients undergoing bypass surgery. The discrimination of the clinical prediction model was determined by the receiver operating characteristic (ROC) curve, and the area under curve (AUC) was 0.928. After adding preoperative frailty assessment, the AUC was improved to 0.939. This study found a significant correlation between preoperative frailty and postoperative complications, mainly in the circulatory system. Conclusion: Preoperative frailty assessment could be a predictive factor for the prognosis of elderly patients undergoing coronary artery bypass grafting. According to our study, frailty assessment and appropriate intervention before bypass surgery may be beneficial to the enhanced recovery after cardiac surgery. Trial registration: The clinical study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (2021-SR-393). All patients signed an informed consent form. [ABSTRACT FROM AUTHOR]

Background and objective Radiotherapy is one of the most common treatments for lung cancer, and about 40%-50% of patients after radiotherapy will appear uncontrolled or recurrence in the case of local tumors. Radioresistance is the predominant cause of local therapeutic failure. Nevertheless, the lack of in vitro radioresistance models is an influential factor obstructing the study of its mechanism. Therefore, the establishment of radioresistant cell lines, H1975DR and H1299DR, was beneficial to explore the mechanism of radioresistance in lung adenocarcinoma. Methods The radioresistant cell lines of H1975DR and H1299DR were obtained from H1975 and H1299 cells irradiated with equal doses of X-rays; Clo-nogenic assays were performed to compare the clone-forming ability of H1975 vs H1975DR cells, H1299 vs H1299DR cells, then fitting cell survival curve by linear quadratic model; The comet assay was employed to examine DNA damage repair and calculate the percentage of DNA tails; The optical microscopy, CCK-8, flow cytometry, Transwell invasion assays were used to compare biological characteristics such as cell morphology, cell proliferation, apoptosis level, cycle distribution, cell migration and invasion; Western blot was carried out to measure the protein expression of DNA damage repair factors, such as DNA-PKcs, 53BP1, RAD51, and p-ATM. Results After five months of continuous irradiation and stable culture, radioresistant cell lines H1975DR and H1299DR were obtained. The cell proliferation activity, clone formation ability and DNA damage repair ability of the two radioresistant cell lines were significantly improved under X-ray irradiation. The proportion of the G2/M phase was markedly decreased and the proportion of the G0/Gj phase was increased. Cell migration and invasion ability were significantly enhanced. Relative expression levels of p-DNA-PKcs (Ser2056), 53BP1 in the nonhomologous end-joining (NHEJ) repair pathway and p-ATM (Ser1981), RAD51 in the homologous recombination (HR) repair pathway were higher than those in H1975 and H1299. Conclusion H1975 and H1299 cell lines can be able to differentiate into lung adenocarcinoma radioresistant cell lines H1975DR and H1299DR by equal dose fractional irradiation, which provided an in vitro cyto-logical model for the study of radiotherapy resistance mechanism of lung cancer patients. [ABSTRACT FROM AUTHOR]

Background and objective Small cell lung cancer (SCLC) with high c-Myc expression is prone to relapse and metastasis, leading to extremely low survival rate. Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaci-clib plays a key role in the treatment of tumors, but the effects and mechanisms on SCLC remain unclear. This study was to analyze the effect and molecular mechanism of Abemaciclib in inhibiting proliferation, migration and invasion of SCLC with high c-Myc expression, with a view to expanding a new direction for reducing the recurrence and metastasis. Methods Proteins interacting with CDK4/6 were predicted using the STRING database. The expressions of CDK4/6 and c-Myc in 31 cases of SCLC cancer tissues and paired adjacent normal tissues were analyzed by immunohistochemistry. The effects of Abemaciclib on the proliferation, invasion and migration of SCLC were detected by CCK-8, colony formation assay, Transwell and migration assay. Western blot was used to detect the expressions of CDK4/6 and related transcription factors. Flow cytometry was used to analyze the effects of Abemaciclib on the cell cycle and checkpoint of SCLC. Results The expression of CDK4/6 was associated with c-Myc by STRING protein interaction network. c-Myc can directly modalize achaete-scute complex homolog 1 (ASCL1), neuronal differentiation 1 (NEUROD1) and Yes-associated protein 1 (YAP1). Moreover, CDK4 and c-Myc regulate the expression of programmed cell death ligand 1 (PD-L1). Immunohistochemistry showed that the expressions of CDK4/6 and c-Myc in cancer tissues were higher than those in adjacent tissues(P<0.0001). CCK-8, colony formation assay, Transwell and migration assay verified that Abemaciclib could effectively inhibit the proliferation, invasion and migration of SBC-2 and H446OE(P<0.0001). Western blot analysis further showed that Abemaciclib not only inhibited CDK4 (P<0.05) and CDK6 (P<0.05), but also affected c-Myc (P<0.05), ASCL1 (P<0.05), NEUROD1 (P<0.05) and YAP1 (P<0.05), which are related to SCLC invasion and metastasis. Flow cytometry showed that Abemaciclib not only inhibited the cell cycle progression of SCLC cells (P<0.0001), but also significantly increased PD-L1 expression on SBC-2 (P<0.01) and H446OE (P<0.001). Conclusion Abemaciclib significantly inhibits the proliferation, invasion, migration and cell cycle progression of SCLC by inhibiting the expressions of CDK4/6, c-Myc, ASCL1, YAP1 and NEUROD1. Abemaciclib can also increase the expression of PD-L1 in SCLC. [ABSTRACT FROM AUTHOR]

Background: Metabolic hypertension (MH) has become the most common type of hypertension in recent years due to unhealthy eating habits and lifestyles of people, such as over-eating alcohol, high fat, and sugar diets (ACHFSDs). Therefore, effective means to combat MH are needed. Previous studies have shown that Panax notoginseng (Burkill) F. H. Chen flower saponins (PNFS) can lower blood pressure in spontaneously hypertensive rats (SHR). However, whether it acts on MH and its mechanism of action remain unclear. Methods: The pharmacodynamic effects of PNFS were evaluated in rats with ACHFSDs-induced MH. The blood pressure, blood biochemical, grip strength, face temperature, vertigo time, and liver index were estimated. The histological changes in the liver and aorta were observed using hematoxylin and eosin staining. The levels of ET-1, TXB2, NO, PGI2, Renin, ACE, Ang II, and ALD in plasma were detected using ELISA. The levels of C3, KLF5, LXRα, and Renin in kidney tissues were measured using qRT-PCR.The expression levels of C3, KLF5, LXRα, and Renin in kidney tissues were examined using Western blotting. Results: In the present study, PNFS was found to reduce blood pressure, face temperature, and vertigo time, increase grip strength and improve dyslipidemia in rats with MH. In addition, PNFS decreased the plasma levels of ET-1 and TXB2, elevated the levels of NO and PGI2, and improved pathological aortic injury. Meanwhile, PNFS decreased the plasma levels of Renin, ACE, Ang II, and ALD. QRT-PCR and Western bolt showed that PNFS downregulated C3, KLF5, LXRα, and Renin protein and mRNA expression in the kidneys of rats with MH. Conclusion: The finding of the present study suggested that PNFS could downregulate C3 and KLF-5 expression in rats with MH, thereby inhibiting the overactivation of the renin–angiotensin–aldosterone system, while improving vascular endothelial function and ultimately reducing blood pressure in rats with MH. [ABSTRACT FROM AUTHOR]

Background: Chronic systemic inflammation may be associated with neurocognitive decline, but the relationships between inflammatory bowel disease and related medications and the risk of Alzheimer's disease remain unclear. Methods: We performed a meta-analysis to evaluate the associations of ulcerative colitis, Crohn's disease and related medications with risk of Alzheimer's disease. We identified cohort and case-control studies by searching PubMed, Embase and Web of Science up to August 2022. Results: Seven eligible studies with 20,174 cases of Alzheimer's disease were included in the meta-analysis. Six studies reported the association between ulcerative colitis and risk of Alzheimer's disease; five studies reported the association between Crohn's disease and risk of Alzheimer's disease. Meta-analysis combining these studies did not reveal any significant association of ulcerative colitis or Crohn's disease with risk of Alzheimer's disease. The pooled relative risks were 1.16 (95%CI: 0.96, 1.41) and 1.17 (95%CI: 0.84, 1.62) for ulcerative colitis and Crohn's disease, respectively. High heterogeneity was detected across the studies. Of note, there was an inverse association between inflammatory bowel disease related medication exposure and risk of Alzheimer's disease. The pooled relative risk of three studies for Alzheimer's disease was 0.86 (95%CI: 0.75, 0.99). No publication bias was detected. Conclusion: This study does not support the association of ulcerative colitis and Crohn's disease with the risk of Alzheimer's disease. However, medications for the treatment of inflammatory bowel disease might be associated with a lower risk of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Objectives. Primary central nervous system lymphoma (PCNSL) usually has a poor prognosis. Cerebrospinal fluid (CSF) interleukin (IL)-10 has shown diagnostic, prognostic, and monitoring value in our previous studies. Cell-free circulating tumor DNA can be detected in the CSF of refractory/relapse cases and has also shown monitoring value. However, information about its monitoring value in newly diagnosed PCNSL patients and comparisons of CSF IL-10 and CSF cell-free DNA (cfDNA) are scarce. Methods. We performed next-generation sequencing on paraffin-embedded tissue and the serial CSF cfDNA of 10 newly diagnosed PCNSL patients and on the baseline CSF cfDNA of 11 other central nervous system lymphoma patients. We also monitored the CSF IL-10 levels of the 10 newly diagnosed PCNSL patients. Results. In seven newly diagnosed PCNSL patients with sufficient baseline CSF cfDNA, six had ≥1 mutated genes in their CSF cfDNA. The most common were MYD88(4/7), PIM1(3/7), MLL2(3/7), and ETV6(2/7). We also identified multiple somatic mutations, most commonly in PIM1. MYD88L265P can be detected in both tumor tissue and CSF cfDNA. The genomic profiles of CFS cfDNA were similar in PCNSL and PIOL patients. Newly diagnosed PCNSL patients with persistently positive cfDNA and negative IL-10 progressed quickly, while those with negative cfDNA and negative IL-10 were in maintenance therapy for more than 18 months. Two patients without cfDNA had increased CSF IL-10 concentrations before disease relapse. These results indicate that negative CSF cfDNA predicts better results, and persistently positive CSF cfDNA predicts disease progression earlier than conventional magnetic resonance imaging. Conclusion. In conclusion, CSF cfDNA is a potential predictor of relapse and progression, which complements the monitoring value of CSF IL-10 in newly diagnosed PCNSL patients. [ABSTRACT FROM AUTHOR]

Background: Arising from chemoreceptor cells, carotid body tumors (CBTs) are rare neoplasms associated with hemodynamics. Perioperative changes in blood pressure (BP) and heart rate (HR) are not completely understood. Methods: This retrospective, observational, controlled study included all CBT patients from 2013 to 2018 in Peking Union Medical College Hospital. Perioperative changes in BP/HR within or between unilateral/bilateral/control groups were investigated. Perioperative details across Shamblin types were also assessed. Results: This study included 108 patients (116 excised CBTs). The postoperative systolic BP and HR increased in both unilateral (mean difference of systolic BP = 5.9mmHg, 95% CI 3.1 ~ 8.6; mean difference of HR = 3.7 bpm, 95% CI 2.6 ~ 4.9) and bilateral (mean difference of systolic BP = 10.3mmHg, 95% CI 0.6 ~ 19.9; mean difference of HR = 8.4 bpm, 95% CI 0.5 ~ 16.2) CBT patients compared with the preoperative measures. Compared with control group, the postoperative systolic BP increased (difference in the alteration = 6.3mmHg, 95% CI 3.5 ~ 9.0) in unilateral CBT patients; both systolic BP (difference in the alteration = 9.2mmHg, 95% CI 1.1 ~ 17.3) and HR (difference in the alteration = 5.3 bpm, 95% CI 1.0 ~ 9.6) increased in bilateral CBT patients. More CBT patients required extra antihypertensive therapy after surgery than controls (OR = 2.5, 95% CI 1.14 ~ 5.5). Maximum tumor diameter, intraoperative vascular injury, continuous vasoactive agent requirement, total fluid volume, transfusion, estimated blood loss, operation duration, postoperative pathology, overall complications, and intensive care unit/hospital lengths of stay significantly varied among Shamblin types. Conclusion: CBT excision may be associated with subtle perioperative hemodynamic changes. Perioperative management of CBT patients necessitates careful assessment, full preparation and close postoperative monitoring. [ABSTRACT FROM AUTHOR]

Background: It is well established that lipoprotein(a)[Lp(a)] play a vital role in atherosclerosis. Whether Lp(a) can predict recurrence of cardiovascular events (CVEs) in prior CVEs patients is still unclear. We aim to investigate its association with subsequent long-term adverse events in this high-risk population. Methods: A total of 4,469 patients with prior CVEs history after PCI were consecutively enrolled and categorized according Lp(a) values of < 10 (low), 10 to 30 (medium), and ≥ 30 mg/dL (high). The primary endpoint was MACCE, a composite of all-cause death, myocardial infarction, stroke and unplanned revascularization. Results: During an average of 5.0 years of follow-up, 1,078 (24.1%) and 206 (4.6%) patients experienced MACCE and all-cause death with 134 (3.0%) of whom from cardiac death. The incidence of MACCE, all-cause death and cardiac death were significantly higher in the high Lp(a) group (p < 0.05). After adjustment of confounding factors, high Lp(a) level remained an independent risk factor for MACCE (adjusted HR 1.240, 95%CI 1.065–1.443, p = 0.006), all-cause death (adjusted HR 1.445, 95%CI 1.023–2.042, p = 0.037) and cardiac death (adjusted HR 1.724, 95%CI 1.108–2.681, p = 0.016). This correlation remained significant when treated as a natural logarithm-transformed continuous variable. This finding is relatively consistent across subgroups and confirmed again in two sensitivity analyses. Conclusions: Our present study confirmed that Lp(a) was an independent predictor for recurrent CVEs in patients with established CVEs, illustrating that Lp(a) level might be a valuable biomarker for risk stratification and prognostic assessment in this high-risk population. [ABSTRACT FROM AUTHOR]

Objectives In the present study, we aimed to assess the prevalence and clinical significance of anti-Ro52 antibodies in a cohort of patients with idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) with different myositis-specific autoantibodies (MSAs). Methods A cohort of 267 IIM-ILD patients, including 62 patients with PM, 126 patients with DM and 79 patients with clinically amyopathic DM (CADM) were retrospectively analysed in this study. Clinical and laboratory findings, pulmonary function tests (PFTs), HRCT patterns and treatment information were compared between patients with and without anti-Ro52 antibodies. The association between prognosis and anti-Ro52 antibodies was also evaluated based on different MSA subgroups. Results Anti-Ro52 antibodies were more frequent in patients with anti-MDA5 (62.1%, P  < 0.01) and anti-Jo1 (64.9%, P  < 0.01) antibodies than in those with other MSAs. The proportion of patients with anti-Jo1 antibodies was higher in the anti-Ro52 antibody-positive group than in the anti-Ro52 antibody-negative group. Patients with anti-Ro52 antibodies were more likely to exhibit the Gottron sign than the anti-Ro52 antibody-negative group (P  < 0.001). Furthermore, it was a predictive factor for rapid progression interstitial lung disease (RP-ILD) (P  = 0.001) and was also associated with a higher mortality rate (log-rank test, P  = 0.001). Furthermore, RP-ILD was more frequently exhibited in anti-MDA5- and anti-Ro52-positive patients. Moreover, anti-Ro52 antibody positivity was closely associated with a higher mortality rate in anti-MDA5-ILD patients (log-rank test, P  < 0.05). Conclusions Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5 and anti-Jo1 antibodies. Within all patients with IIM-ILD, those with anti-Ro52 autoantibodies had a higher frequency of RP-ILD and a poorer prognosis, especially in the anti-MDA5 antibody subgroup. [ABSTRACT FROM AUTHOR]

Background: Understanding genetic influences on Alzheimer's disease (AD) may improve early identification. Polygenic hazard score (PHS) is associated with the age of AD onset and cognitive decline. It interacts with other risk factors, but the nature of such combined effects remains poorly understood. Materials and methods: We examined the effect of genetic risk and hippocampal atrophy pattern on episodic memory in a sample of older adults ranging from cognitively normal to those diagnosed with AD using structural MRI. Participants included 51 memory unimpaired normal control (NC), 69 mild cognitive impairment (MCI), and 43 AD adults enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Hierarchical linear regression analyses examined the main and interaction effects of hippocampal subfield volumes and PHS, indicating genetic risk for AD, on a validated episodic memory composite score. Diagnosis-stratified models further assessed the role of PHS. Results: Polygenic hazard score moderated the relationship between right fimbria/hippocampus volume ratio and episodic memory, such that patients with high PHS and lower volume ratio had lower episodic memory composite scores [ΔF = 6.730, p = 0.011, ΔR² = 0.059]. This effect was also found among individuals with MCI Δ1F = 4.519, p = 0.038, ΔR² = 0.050]. In contrast, no interaction effects were present for those NC or AD individuals. A follow-up mediation analysis also indicated that the right fimbria/hippocampus volume ratio might mediate the link between PHS and episodic memory performance in the MCI group, whereas no mediation effects were present for those NC or AD individuals. Conclusion: These findings suggest that the interaction between AD genetic risk and hippocampal subfield volume ratio increases memory impairment among older adults. Also, the results highlighted a potential pathway in which genetic risk affects memory by degrading hippocampal subfield volume ratio in cognitive decline subjects. [ABSTRACT FROM AUTHOR]

Background. Activation of chronic hepatitis B virus (HBV) infection is an important cause of acute-on-chronic liver failure (ACLF). However, the effect of HBV-ACLF episode on hepatocellular carcinoma (HCC) occurrence remains largely unknown. Methods. A total of 769 HBV-ACLF patients and 2114 HBV-related chronic liver disease (HBV-CLD) patients diagnosed between August 1998 and December 2011 were enrolled in this prospective cohort study. Of the HBV-CLD patients, 380 received lifetime antiviral treatment with nucleos(t)ide analogues. Propensity score matching was applied to reduce baseline differences between HBV-ACLF and HBV-CLD cohorts. Results. The survival rate of HBV-ACLF patients was 53.6%, 50.3%, 47.8%, and 46.2% at 90-day, 1-year, 5-year, and 10-year, respectively. The cumulative incidence of HCC was lower in HBV-ACLF cohort with 369 eligible patients survived for >90 days than in HBV-CLD cohort with the 380 patients (5.77/1,000 vs. 9.78/1,000 person-years, p = 0.0497). HBV-ACLF episode decreased HCC risk regardless of liver cirrhosis, and in patients without family history of HCC. Multivariate Cox analyses indicated that male, increasing age, liver cirrhosis, and platelet count (≤100 × 109/L) increased, whereas HBV-ACLF episode decreased, HCC risk independently. In the propensity score-matched cohorts, HBV-ACLF episode reduced HCC incidence (10.20/1,000 vs. 4.66/1,000 person-years, p = 0.0326). The area under curve of nomogram was 0.812 for 3-year HCC probability. Conclusions. HBV-ACLF episode decreases HCC occurrence in chronic HBV patients. Older age and liver cirrhosis independently increased HCC occurrence. A nomogram-enrolled episode of ACLF reliably predicts the occurrence of HCC. [ABSTRACT FROM AUTHOR]

Background. Pulmonary alveolar proteinosis (PAP) is a rare disorder which is characterized by the accumulation of excessive surfactant lipids and proteins in alveolar macrophages and alveoli. Oral statin therapy has been reported to be a novel therapy for PAP with hypercholesterolemia. We aimed to evaluate the safety and efficacy of oral statin therapy for PAP without hypercholesterolemia. Methods. In a prospective real-world observational study, 47 PAP patients without hypercholesterolemia were screened. Oral statin was initiated as therapy for these PAP patients with 12 months of follow-up. Results. Forty PAP patients completed the study. 26 (65%) of 40 PAP patients responded to statin therapy according to the study criteria. Partial pressure of arterial oxygen (PaO2) and percentage of diffusion capacity predicted (DLCO%) significantly increased while disease severity score (DSS) and radiographic abnormalities decreased after 12 months of statin therapy (all p < 0.05). The factors associated with response were higher levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody and baseline total cholesterol/high-density lipoprotein cholesterol (TC/HDL) (p = 0.015 and p = 0.035 , respectively). The area under the receiver operating characteristic curve (AUROC) of dose of atorvastatin for predicting the response to statin therapy for PAP was 0.859 (95% CI: 0.738-0.979, p < 0.001). The cutoff dose of atorvastatin was 67.5 mg daily with their corresponding specificity (64.3%) and sensitivity (96.2%). No severe side effects were observed during the study. Conclusions. In PAP patients without hypercholesterolemia, statin therapy resulted in improvements in arterial blood gas (ABG) measurement, pulmonary function, and radiographic assessment. [ABSTRACT FROM AUTHOR]

Simple Summary: Identifying new prognostic markers can provide a reference for the treatment of lung adenocarcinoma (LUAD) to improve its prognosis. Circadian rhythm disturbances are closely linked to the initiation, progression and prognosis of lung cancer. We aimed to explore the value of circadian miRNA (cmiRNA) as a prognostic marker of LUAD. A prognostic signature comprising seven pairs of cmiRNAs was established, and it exhibited excellent predictive value for overall and progression-free survival. High-risk patients showed higher sensitivity to primary chemotherapy drugs and targeted medicine compared with low-risk patients. Overall, the novel circadian-related miRNA pair signature could provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for LUAD. The cmiRNA–Cgenes network and corresponding enrichment analysis might provide clues for studying the underlying circadian dysregulation mechanisms involved in the progression of LUAD in the future. Lung adenocarcinoma (LUAD) is the primary histological subtype of lung cancer with a markedly heterogeneous prognosis. Therefore, there is an urgent need to identify optimal prognostic biomarkers. We aimed to explore the value of the circadian miRNA (cmiRNA) pair in predicting prognosis and guiding the treatment of LUAD. We first retrieved circadian genes (Cgenes) from the CGDB database, based on which cmiRNAs were predicted using the miRDB and mirDIP databases. The sequencing data of Cgenes and cmiRNAs were retrieved from TCGA and GEO databases. Two random cmiRNAs were matched to a single cmiRNA pair. Finally, univariate Cox proportional hazard analysis, LASSO regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature consisting of seven cmiRNA pairs. The signature exhibited good performance in predicting the overall and progression-free survival. Patients in the high-risk group also showed lower IC50 values for several common chemotherapy and targeted medicines. In addition, we constructed a cmiRNA–Cgenes network and performed a corresponding Gene Ontology and Gene Set enrichment analysis. In conclusion, the novel circadian-related miRNA pair signature could provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for LUAD. [ABSTRACT FROM AUTHOR]

Objective: Many studies have explored the neural mechanisms of cognitive impairment in chronic obstructive pulmonary disease (COPD) patients using the functional MRI. However, the dynamic properties of brain functional networks are still unclear. The purpose of this study was to explore the changes in dynamic functional network attributes and their relationship with cognitive impairment in stable COPD patients. Materials and methods: The resting-state functional MRI and cognitive assessments were performed on 19 stable COPD patients and 19 age-, sex-, and education-matched healthy controls (HC). We conducted the independent component analysis (ICA) method on the resting-state fMRI data, and obtained seven resting-state networks (RSNs). After that, the static and dynamic functional network connectivity (sFNC and dFNC) were respectively constructed, and the differences of functional connectivity (FC) were compared between the COPD patients and the HC groups. In addition, the correlation between the dynamic functional network attributes and cognitive assessments was analyzed in COPD patients. Results: Compared to HC, there were significant differences in sFNC among COPD patients between and within networks. COPD patients showed significantly longer mean dwell time and higher fractional windows in weaker connected State I than that in HC. Besides, in comparison to HC, COPD patients had more extensive abnormal FC in weaker connected State I and State IV, and less abnormal FC in stronger connected State II and State III, which were mainly located in the default mode network, executive control network, and visual network. In addition, the dFNC properties including mean dwell time and fractional windows, were significantly correlated with some essential clinical indicators such as FEV1, FEV1/FVC, and c-reactive protein (CRP) in COPD patients. Conclusion: These findings emphasized the differences in sFNC and dFNC of COPD patients, which provided a new perspective for understanding the cognitive neural mechanisms, and these indexes may serve as neuroimaging biomarkers of cognitive performance in COPD patients. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction may contribute to the increased morbidity and mortality associated with coronary heart disease (CHD). Flow-mediated dilatation (FMD) is the most popular noninvasive method for vascular endothelial function evaluation. This meta-analysis aimed to investigate the association between FMD and CHD. We searched the publications listed in the PubMed, Web of Science, Scopus, and Embase databases. Stata 14 software was used to analyze the data. Standardized mean difference (SMD) was used to calculate FMD levels, and the effect sizes were expressed with a 95% confidence interval (CI). I2 statistics were used to evaluate statistical heterogeneity. In this meta-analysis, 9 studies enrolled a total number of 943 participants, including 534 (56.63%) patients with CHD and 409 controls (43.37%). We found that patients with CHD showed a significantly lower FMD than the controls (SMD −0.706%; 95% CI: −0.985, −0.427; P = 0.001) with high heterogeneity. In addition, funnel plot analysis suggested asymmetry that could be evidence of publication bias. But sensitivity analyses show that there were no influential studies. This meta-analysis provides evidence that patients with CHD show a significantly lower FMD than controls and highlights the literature on FMD as a hallmark in CHD diseases. [ABSTRACT FROM AUTHOR]

Introduction. Rheumatoid arthritis (RA) is an autoimmune disorder associated with joint damage and attendant cardiovascular complications. Wedelolactone (Wed), derived from Eclipta alba, possesses anti-inflammatory activity. Whether Wed regulates RA inflammation and related heart damage remains unknown. Material and methods. A murine model of collagen-induced arthritis (CIA) was well-established by two subcutaneous injections of type II collagen (days 0 and 21). Wed was then administered via intraperitoneal injection every other day from day 28 to day 48. Joint swelling was monitored and paw thickness was calculated. Histopathological changes in synovial tissues or ankle cartilage were evaluated by hematoxylin and eosin (H&E) and Safranin O-Fast Green staining. The concentrations of inflammatory factors in serum and synovial tissues were detected by ELISA. The qRT-PCR, Western blotting, immunohistochemistry (IHC), and immunofluorescence (IF) were performed to assess receptor activator of nuclear factor kappa ligand (RANKL), matrix metalloprotease (MMP)-3, NLRP3, caspase-1 (pro- and cleaved forms), p-p65, IκBα, p-IκBα, p65, asmooth-actin 2 (ACTA2), collagen type I and E-cadherin expression. H&E and Masson staining were used to assess the pathological alterations in the heart. Results. Treatment with Wed ameliorated ankle joint swelling and cartilage degradation. Wed decreased the infiltration of inflammatory cells, the release of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-a, and IL-18), and the expression of RANKL and MMP-3 in serum and synovial tissues of CIA mice. Moreover, Wed increased the expression of NLRP3 and cleaved-caspase-1 in the synovium, leading to IL-1ß and IL-18 secretion. Nuclear factor-kappaB (NF-κB) activation in synovial tissues was suppressed by Wed, as manifested by reduced phosphorylation of p65 and IκBa and nuclear translocation of p65. Furthermore, Wed reduced in CIA mice heart weight/body weight ratio and dampened cardiac inflammation and fibrosis that was accompanied at the mRNA level by down-regulation of ACTA2 and collagen I and up-regulation of E-cadherin. Conclusions. These findings suggested that Wed attenuated synovial inflammation and joint damage in a mouse model of RA via inhibiting NF-κB/NLRP3 inflammasome activation, and ameliorated RA-induced cardiac complications. [ABSTRACT FROM AUTHOR]