Impact of CYP2A6 Gene Polymorphism on the Efficacy and Safety of S-1 Therapy in Patients with Gastric Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: The relationship of CYP2A6 polymorphisms with S-1 therapy outcomes in gastric cancer is unclear. This review aims to assess the association between CYP2A6 gene polymorphisms (CYP2A6*4, *7, *9, *10) and S-1 therapy outcomes in gastric cancer, aiming to identify predictive markers for S-1 efficacy and adverse reactions. METHODS: We searched seven databases, using random or fixed effect models to calculate hazard ratio (HR) and 95% confidence interval (CI) based on study heterogeneity. RESULTS: A total of 1143 articles were retrieved from multiple online databases as of March 28, 2023. After screening, seven articles containing seven investigations were included in the meta-analysis. Our results revealed a significant association between the CYP2A6 polymorphism site and the overall survival (OS) of V/V patients compared to W/W or W/V patients (HR=2.73, 95%CI:1.45-5.14, P=0.002). S-1 was more beneficial for W/W or W/V patients than V/V patients in terms of Progression-Free Survival (PFS) (HR=3.15,95%CI:1.47-6.75, P=0.003). There was no association between CYP2A6 polymorphism and hematological adverse reactions (OR=0.52, 95%CI: 0.23-1.15, P=0.104). CONCLUSION: CYP2A6 polymorphisms correlate with S-1 efficacy (OS, PFS) in gastric cancer, suggesting their potential as predictive markers. However, the generalizability of findings is limited by the small number of studies from Eastern countries and variations in chemotherapy regimens and detection methods. Further large-scale studies are needed to confirm these associations.

Preparation and characterization of pectin-alginate-based microbeads reinforced by nano montmorillonite filler for probiotics encapsulation: Improving viability and colonic colonization.

Hydrogel microbeads can be used to enhance the stability of probiotics during gastrointestinal delivery and storage. In this study, the pectin-alginate hydrogel was enhanced by adding montmorillonite filler to produce microbeads for encapsulating Lactobacillus kefiranofaciens (LK). Results showed that the viscosity of biopolymer solutions with 1 % (PAMT1) and 3 % (PAMT3) montmorillonite addition was suitable for producing regular-shaped microbeads. A layered cross-linked network was formed on the surface of PAMT3 microbeads through electrostatic interaction between pectin-alginate and montmorillonite filler, and the surrounding LK with adsorbed montmorillonite was encapsulated inside the microbeads. PAMT3 microbeads reduced the loss of viability of LK when passing through the gastric acid environment, and facilitated the slow release of LK in the intestine and colonic colonization. The maximum decrease in viability among all filler groups was 1.21 log CFU/g after two weeks of storage, while PAMT3 freeze-drying microbeads only decreased by 0.46 log CFU/g, indicating that the gel layer synergized with the adsorbed layer to provide dual protection for probiotics. Therefore, filler-reinforced microbeads are a promising bulk encapsulation carrier with great potential for the protection and delivery of probiotics and can be developed as food additives for dairy products.

Learning Middle-Latitude Cyclone Formation up in the Air: Student Learning Experience, Outcomes, and Perceptions in a CAVE-Enabled Meteorology Class.

Cave Automatic Virtual Environment (CAVE) is a virtual reality (VR) environment that has not been fully studied due to its high cost and complexity in system integration. Previous CAVE-related studies mainly focused on comparing its effectiveness with other learning media, such as textbooks, desktop VR, or head-mounted display (HMD) VR. In this study, through the utilization of CAVE in a meteorology class, we concentrated on CAVE itself, measured how CAVE impacted learners' learning outcomes before and after using CAVE in an actual ongoing undergraduate-level class, and investigated how learners perceived their learning experiences. Quantitative data were collected to examine the students' knowledge acquisition and learning experience. We also triangulated the quantitative results with qualitative data from the interviews regarding learners' perceptions of the CAVE-enabled class and their knowledge mastery. The results indicated that their learning outcomes increased through learning with CAVE and that their perceptions of immersion, presence, and engagement significantly correlated with each other. The interview results showed a great fondness of and satisfaction with the learning experience, group collaboration, and effectiveness of the CAVE-enabled class from the learners. We also learned that the learners' learning experiences in CAVE could be further improved if we provided them with more learner-environment interaction, offered them a better sense of immersion, and reduced cybersickness. Implications of these findings are discussed.

Diagnostic value of Procalcitonin, C-reactive protein-to-lymphocyte ratio (CLR), C-reactive protein and neutrophil-to-lymphocyte ratio (NLR) for predicting patients with Bacteraemia in the intensive care unit.

BACKGROUND: To explore the diagnostic value of procalcitonin (PCT), C-reactive protein-to-lymphocyte ratio (CLR), C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) for predicting patients with bacteremia in the intensive care unit (ICU). METHODS: This case-control study included 359 patients with suspected bacteremia were divided into a bacteremia group (n = 152) and a control group (n = 207) from September 2018 to April 2023. Patient data were collected using a laboratory information system (LIS). ROC curves for PCT, CLR, CRP, and NLR in predicting patients with bacteremia. RESULTS: For PCT, CLR, CRP and NLR to predict patients with bacteremia in the ICU, the AUCs were 0.991(95%CI: 0.974-0.998), 0.960(95%CI: 0.935-0.978), 0.955(95%CI: 0.928-0.974), and 0.898(95%CI:0.862-0.927), respectively; the optimal thresholds were 0.248 ng/mL, 47.52 mg/109, 48.32 mg/L, and 6.51, respectively; the sensitivities were 95.4(95%CI: 90.7-98.1), 88.2(95%CI: 81.9-92.8), 87.5(95%CI: 81.2-92.3), and 86.8(95%CI:80.4-91.8), respectively; and the specificities were 95.7(95%CI: 91.9-98.0), 90.8(95%CI: 86.0-94.4), 90.3(95%CI: 85.5-94.0), and 85.0(95%CI:79.4-89.6), respectively. The sensitivities of PCT, CLR, CRP and NLR for predicting bacteremia due to E. coli infection are as high as over 90%, the specificity of PCT is 100, and the sensitivity of NLR is 100. The sensitivity of CRP for predicting bacteremia due to non-Enterobacer infection is 100. CONCLUSIONS: Compared with those in the control group, PCT, CLR, CRP and NLR were significantly greater in the bacteremia group. The PCT, CLR, CRP, and NLR can all predict the occurrence of bacteremia. The PCT had the highest sensitivity and specificity in predicting bacteremia in ICU patients.

Cerebral circulation time on DSA after thrombectomy associated with hemorrhagic transformation in acute ischemic stroke.

BACKGROUND: To investigate the association between cerebral circulation time (CCT) on digital subtraction angiography immediately after thrombectomy and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). METHODS: Retrospectively enrolled consecutive AIS patients presented with large vessel occlusion who received thrombectomy and achieved successful recanalization between January 2019 and June 2021. The time interval from the beginning of the siphon segment of internal carotid artery visualization until the end of the arterial phase during cerebral angiography was calculated as CCT. The independent association of CCT with HT was evaluated using logistic regression analyses. The receiver operating characteristic curve was analyzed to evaluate the association between CCT and HT. RESULTS: Two hundred and twenty-four patients were included, of whom 86 (38.4%) suffered HT. Compared with patients without HT, patients with HT were of advanced age, less commonly male, had more diabetes mellitus, had higher baseline National Institutes of Health Stroke Scale score, lower Alberta Stroke Program Early Computed Tomographic Score, and shorter CCT (P < 0.05). Multivariable logistic regression suggested that CCT was independently associated with HT (adjusted odds ratio, 0.170; 95% confidence interval, 0.004-0.450; P < 0.001). According to the receiver operating characteristic curve, the optimal cut-off value for the strong correlation between CCT and HT was 1.72 s, which had 76.6% sensitivity, 81.6% specificity, and the area under the curve was 0.846. CONCLUSION: Shorter post-thrombectomy CCT was independently associated with HT.

Patient preferences and willingness to pay for central venous access devices in breast cancer: A multicenter discrete choice experiment.

BACKGROUND: Despite being a significant management decision in clinical or nursing practice, there is limited understanding of the preferences regarding risks, benefits, costs, and other attributes of patients with breast cancer when selecting peripherally inserted central catheters or totally implanted ports. The objective of this study is to investigate the preferences of patients with breast cancer who require chemotherapy when selecting an optimal central venous access device. METHODS: Data on patients' preferences for central venous access devices were collected using a face-to-face discrete choice experiment from the oncology departments of three public hospitals in China representing the eastern (Zhejiang province), central (Henan province), and western (Sichuan province) regions. The study used six attributes to describe the preferences of breast cancer patients for central venous access devices, including out-of-pocket cost, limitations in activities of daily living, catheter maintenance frequency, risk of catheter-related thrombosis, risk of catheter-related infection, and size of incision. Data were analyzed using a conditional logit model and mixed logit model. The marginal willingness to pay (mWTP) was calculated by assessing the ratio of the preference for other attributes to the preference for out-of-pocket cost. RESULTS: A total of 573 respondents completed the survey. The discrete choice experiment results showed that respondents strongly preferred a central venous access device with a catheter maintenance frequency of one time a month (vs four times a month, ß = 1.188, p < 0.001), the lower risk of catheter-related thrombosis (2 % vs 10 %, ß = 1.068; p < 0.001) and lower risk of catheter-related infection (2 % vs 8 % risk: ß = 0.824; p < 0.001). Respondents were willing to pay CNY ¥11,968.1 (US$1776.5) for a central venous access device with a catheter maintenance frequency of one time a month rather than four times a month, ¥10,753.6 (US$1596.2) for a central venous access device with 2 % thrombosis risk over one with 10 %, and ¥8302.0 (US$1232.3) for a central venous access device with 2 % infection risk over one with 8 %. Respondents with longer travel time to the hospital, younger than 50 years old, and with urban employee basic medical insurance were willing to pay more for an improvement in the attributes. CONCLUSIONS: These findings suggest that patients with breast cancer were mainly concerned with the out-of-pocket cost, catheter maintenance frequency, risk of catheter-related thrombosis and risk of catheter-related infection when choosing a central venous access device for the delivery of chemotherapy. In clinical or nursing practice, when making central venous access device recommendation for young patients and those who live far from hospitals, totally implanted ports may be a preferable choice.

Patient Welfare Implications of Indication-Specific Value-Based Pricing of Multi-Indication Drugs.

OBJECTIVES: Indication-specific value-based pricing (ISVBP) is a mechanism that allows the prices of multi-indication drugs to vary across indications by aligning the drug prices with value. However, the overall impact of ISVBP on patients across indications is uncertain. This study examines the theoretical welfare effects of ISVBP for multi-indication drugs and compares consumer surplus under ISVBP and single pricing, the latter of which is based on the weighted average value. METHODS: We considered a healthcare system with government-negotiated drug prices based on the value of drugs. We assumed a drug with 2 indications and 1 relevant comparator for each indication. The value of the drug was uniformly distributed among the patients of each indication in the base case. We also considered alternative scenarios with exponentially and Pareto distributed drug values. Numerical simulations were conducted to explore potential settings where ISVBP was welfare-improving for patients compared with single pricing. RESULTS: The theoretical analysis showed that the consumer surplus change was strictly non-positive from single pricing to ISVBP. Therefore, it was not welfare-improving for patients in the settings of interest. Numerical simulations confirmed this result across various scenarios of value distributions. CONCLUSIONS: This study provides insights into the patient welfare implications of ISVBP for multi-indication drugs. We did not identify conditions under which ISVBP can enhance overall patient well-being, suggesting that it should be implemented cautiously. Future research should examine dynamic welfare implications related to innovation incentives because they may significantly affect population health in the future.

Prenatal MRI assessment of mediastinal shift angle as a feasible and effective risk stratification tool in isolated right-sided congenital diaphragmatic hernia.

OBJECTIVES: To develop a mediastinal shift angle (MSA) measurement method applicable to right-sided congenital diaphragmatic hernia (RCDH) in fetal MRI and to validate the predictive value of MSA in RCDH. METHODS: Twenty-seven fetuses with isolated RCDH and 53 controls were included in our study. MSA was measured on MRI axial image at the level of four-chamber view of the fetal heart. The angle between the sagittal midline landmark line and the left boundary landmark line touching tangentially the lateral wall of the left ventricle was used to quantify MSA for RCDH. Appropriate statistical analyses were performed to determine whether MSA can be regarded as a valid predictive tool for postnatal outcomes. Furthermore, predictive performance of MSA was compared with that of lung area to head circumference ratio (LHR), observed/expected LHR (O/E LHR), total fetal lung volume (TFLV), and observed/expected TFLV (O/E TFLV). RESULTS: MSA was significantly higher in the RCDH group than in the control group. MSA, LHR, O/E LHR, TFLV, and O/E TFLV were all correlated with postnatal survival, pulmonary hypertension (PH), and extracorporeal membrane oxygenation (ECMO) therapy (p < 0.05). Value of the AUC demonstrated good predictive performance of MSA for postnatal survival (0.901, 95%CI: (0.781-1.000)), PH (0.828, 95%CI: (0.661-0.994)), and ECMO therapy (0.813, 95%CI: (0.645-0.980)), which was similar to O/E TFLV but slightly better than TFLV, O/E LHR, and LHR. CONCLUSIONS: We developed a measurement method of MSA for RCDH for the first time and demonstrated that MSA could be used to predict postnatal survival, PH, and ECMO therapy in RCDH. CLINICAL RELEVANCE STATEMENT: Newly developed MRI assessment method of fetal MSA in RCDH offers a simple and effective risk stratification tool for patients with RCDH. KEY POINTS: • We developed a measurement method of mediastinal shift angle for right-sided congenital diaphragmatic hernia for the first time and demonstrated its feasibility and reproducibility. • Mediastinal shift angle can predict more prognostic information other than survival in right-sided congenital diaphragmatic hernia with good performance. • Mediastinal shift angle can be used as a simple and effective risk stratification tool in right-sided congenital diaphragmatic hernia to improve planning of postnatal management.

MFA-UNet: a vessel segmentation method based on multi-scale feature fusion and attention module.

Introduction: The accurate segmentation of retinal vessels is of utmost importance in the diagnosis of retinal diseases. However, the complex vessel structure often leads to poor segmentation performance, particularly in the case of microvessels. Methods: To address this issue, we propose a vessel segmentation method composed of preprocessing and a multi-scale feature attention network (MFA-UNet). The preprocessing stage involves the application of gamma correction and contrast-limited adaptive histogram equalization to enhance image intensity and vessel contrast. The MFA-UNet incorporates the Multi-scale Fusion Self-Attention Module(MSAM) that adjusts multi-scale features and establishes global dependencies, enabling the network to better preserve microvascular structures. Furthermore, the multi-branch decoding module based on deep supervision (MBDM) replaces the original output layer to achieve targeted segmentation of macrovessels and microvessels. Additionally, a parallel attention mechanism is embedded into the decoder to better exploit multi-scale features in skip paths. Results: The proposed MFA-UNet yields competitive performance, with dice scores of 82.79/83.51/84.17/78.60/81.75/84.04 and accuracies of 95.71/96.4/96.71/96.81/96.32/97.10 on the DRIVE, STARE, CHASEDB1, HRF, IOSTAR and FIVES datasets, respectively. Discussion: It is expected to provide reliable segmentation results in clinical diagnosis.

Population impact of fine particulate matter on tuberculosis risk in China: a causal inference.

BACKGROUND: Previous studies have suggested the potential association between air pollution and tuberculosis incidence, but this association remains inconclusive and evidence to assess causality is particularly lacking. We aimed to draw causal inference between fine particulate matter less than 2.5 µm in diameter (PM2.5) and tuberculosis in China. METHODS: Granger causality (GC) inference was performed within vector autoregressive models at levels and/or first-differences using annual national aggregated data during 1982-2019, annual provincial aggregated data during 1982-2019 and monthly provincial aggregated data during 2004-2018. Convergent cross-mapping (CCM) approach was used to determine the backbone nonlinear causal association based on the monthly provincial aggregated data during 2004-2018. Moreover, distributed lag nonlinear model (DLNM) was applied to quantify the causal effects. RESULTS: GC tests identified PM2.5 driving tuberculosis dynamics at national and provincial levels in Granger sense. Empirical dynamic modeling provided the CCM causal intensity of PM2.5 effect on tuberculosis at provincial level and demonstrated that PM2.5 had a positive effect on tuberculosis incidence. Then, DLNM estimation demonstrated that the PM2.5 exposure driven tuberculosis risk was concentration- and time-dependent in a nonlinear manner. This result still held in the multi-pollutant model. CONCLUSIONS: Causal inference showed that PM2.5 exposure driving tuberculosis, which showing a concentration gradient change. Air pollutant control may have potential public health benefit of decreasing tuberculosis burden.

Pick's disease presenting with corticobasal syndrome: A case report and clinicopathological review.

Pick's disease (PiD) is a rare form of frontal temporal lobar degeneration. The pathognomonic feature is atrophy of the frontotemporal lobes and intraneuronal deposits of 3R-τ inclusions, the Pick body. Corticobasal syndrome (CBS) is an atypical parkinsonian syndrome with a heterogeneous spectrum of underlying pathologies. We report a case of clinically diagnosed CBS with a post-mortem diagnosis of PiD and conduct a clinicopathological review of the literature on this unusual presentation.

Cost-effectiveness of cytomegalovirus vaccination for females in China: A decision-analytical Markov study.

BACKGROUND: The global burden of disease caused by congenital cytomegalovirus (CMV) infection is high. Previous modeling studies have suggested that CMV vaccination may be cost-effective in developed countries. Congenital CMV infection is more likely driven by maternal non-primary infection in China. We aimed to measure the effectiveness and cost-effectiveness of population-level CMV vaccination in Chinese females. METHODS: A decision tree Markov model was developed to simulate potential CMV vaccination strategies in a multi-cohort setting, with a population size of 1,000,000 each for the infant, adolescent (10-year-old) and young adult (20-year-old) cohorts. The hypothetical vaccines were assumed to have 50% efficacy, 20 years of protection, 70% coverage, at a price of US$120/dose for base-case analysis. Costs and disability-adjusted life years (DALYs) were discounted by 3% per year and the vaccination would be considered cost-effective if an incremental cost-effectiveness ratio (ICER) was lower than 2021 Chinese per capita GDP (US$12,500). FINDINGS: For the pre-infection (PRI) vaccine efficacy type, the adolescent strategy was the most cost-effective, with an ICER of US$12,213 (12,134 to 12,291) pre DALY averted, compared with the next best strategy (young adult strategy). For pre- and post-infection (P&PI) efficacy type, the young adult strategy was the most cost-effective as it was cost-saving. In one-way analysis varying the PRI vaccine price, the infant strategy, adolescent strategy and the young adult strategy would be a dominant strategy over others if the vaccine cost ≤US$60, US$61-121 and US$122-251 per dose respectively. In contrast, the young adult strategy continued to be the preferred strategy until the P&PI vaccine price exceeded US$226/dose. Our main results were robust under a wide variety of sensitivity analyses and scenario analyses. INTERPRETATION: CMV vaccination for females would be cost-effective and even cost-saving in China. Our findings had public health implications for control of CMV diseases.

Adipocyte-Derived Extracellular Vesicles: Small Vesicles with Big Impact.

While increasing numbers of studies have established that adipose tissue plays a vital role in balancing energy intake and energy expenditure as both an energy and an endocrine organ, the detailed functions of adipose tissue remain unclear. Adipose tissues are complex, with multiple resident cell populations that communicate to diverse cells and organs via local and systemic metabolic, thermal, and inflammatory signaling. In normal physiology, adipose tissue-derived extracellular vesicles mediate the regulation of energy storage/consumption in adipose tissue, liver, and muscle. In a pathological sense, fat-derived extracellular vesicles can promote the progression of obesity, endocrine diseases, cancer, and reproductive system disorders. In this review, we demonstrate that adipocyte-derived extracellular vesicles function not only in physiological balance but also in the pathological process. We aim to illustrate the impact of adipocyte-derived extracellular vesicles and their value in understanding both homeostasis and disorders.

The biological roles of CD24 in ovarian cancer: old story, but new tales.

CD24 is a glycosylphosphatidylinositol linked molecular which expressed in diverse malignant tumor cells, particular in ovarian carcinoma cells and ovarian carcinoma stem cells. The CD24 expression is associated with increased metastatic potential and poor prognosis of malignancies. CD24 on the surface of tumor cells could interact with Siglec-10 on the surface of immune cells, to mediate the immune escape of tumor cells. Nowadays, CD24 has been identified as a promising focus for targeting therapy of ovarian cancer. However, the roles of CD24 in tumorigenesis, metastasis, and immune escape are still not clearly demonstrated systematically. In this review, we i) summarized the existing studies on CD24 in diverse cancers including ovarian cancer, ii) illustrated the role of CD24-siglec10 signaling pathway in immune escape, iii) reviewed the existing immunotherapeutic strategies (targeting the CD24 to restore the phagocytic effect of Siglec-10 expressing immune cells) based on the above mechanisms and evaluated the priorities in the future research. These results might provide support for guiding the CD24 immunotherapy as the intervention upon solid tumors.

Intolerance of uncertainty enhances generalisation of cued conditioned threat: An event-related potential study.

Overgeneralisation is one of the aetiologies of anxiety disorders and is closely associated with elevated intolerance of uncertainty (IU) levels. However, the underlying mechanisms are unclear. Considering the inconsistency of previous results and the high sensitivity of IU to uncertainty, the present study investigated the effect of IU on threat generalisation in predictable and unpredictable conditions. We compared self-reported unconditioned stimuli (US) expectancy and event-related potentials (ERPs) during generalisation in high IU (n = 34) and low IU (n = 35) participants. The results indicated that high IU was associated with higher US expectancy for generalisation stimuli (GS) than with low IU. At the electrophysiological level, compared to low IU, high IU showed increased P1 to ambiguous GS as well as decreased early late positive potential (LPP) to GS in unpredictable conditions, and no differential response to GS in late LPP in predictable conditions. These findings suggest that IU enhances threat generalisation and may be related to increased early automatic attention to ambiguous stimulus and inadequate late elaborate processing in a high uncertainty context. These findings might contribute to the treatment of mood disorders characterized by high IU.

SPTBN2 regulates endometroid ovarian cancer cell proliferation, invasion and migration via ITGB4­mediated focal adhesion and ECM receptor signalling pathway.

Ovarian cancer is as a major contributor to gynaecologic death globally. The present study aimed to investigate the regulatory role of spectrin ß non-erythrocytic 2 gene (SPTBN2) in endometroid ovarian cancer and its mechanism of action. According to the Gene Expression Profiling Interactive Analysis (GEPIA) database, SPTBN2 expression is elevated in ovarian cancer tissues and higher SPTBN2 expression indicated a worse prognosis. The present study assessed SPTBN2 mRNA and protein expression levels by reverse transcription-quantitative PCR and western blotting, respectively. Cell viability, proliferation, migration and invasion were assessed with Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine incorporation, wound healing and Transwell assays, respectively. SPTBN2 expression was notably enhanced in ovarian cancer cell lines, especially in A2780 cells compared with HOSEPiC cells (P<0.001). Following transfection with small interfering (si)RNA targeting SPTBN2, the viability, proliferation, migration and invasion of A2780 cells were decreased compared with those of A2780 cells transfected with siRNA-NC (P<0.001). Gene Set Enrichment Analysis database revealed that SPTBN2 was primarily enriched in 'focal adhesion' and 'extracellular matrix (ECM)-receptor interaction', whereas SPTBN2 was significantly associated with integrin ß4 (ITGB4) in the GEPIA database. In addition, rescue experiments were performed to determine the mechanism of SPTBN2 in endometroid ovarian cancer. ITGB4 overexpression reversed the inhibitory effects of the SPTBN2 knockdown on viability, proliferation, migration and invasion of A2780 cells (P<0.05). The impacts of SPTBN2 on the expression of focal adhesion and downstream ECM receptor signalling-related proteins, including Src and p-FAK/FAK, were significantly reversed by ITGB4 overexpression (P<0.01). Collectively, SPTBN2 may regulate endometroid ovarian cancer cell proliferation, invasion and migration through the ITGB4-mediated focal adhesion and ECM receptor signalling pathway.

Individual differences in contextual threat generalisation and uncertainty: The role of intolerance of uncertainty.

Threat generalisation is an adaptive process that is essential for individual survival. In contrast, over-generalisation is a pathological process that underlies the development of anxiety disorders. Intolerance of uncertainty (IU) is an individual characteristic known to influence threat generalisation by altering the responses to threat in uncertain situations. However, how it affects contextual threat generalisation remains unclear. Here, we used a novel paradigm to investigate whether contextual threat generalisation varied between individuals depending on their IU level (high or low) and the predictability of a situation (predictable or unpredictable). We analysed shock expectancy in 82 participants (age: 18-27 years) during threat acquisition and generalisation. Results showed that compared with the low IU group, the high IU group exhibited increased contextual threat generalisation to threat-related cues in unpredictable situation. These findings suggest that IU could be a marker for anxiety disorder susceptibility, as well as a target for anxiety treatment.

The association between total bile acid and bone mineral density among patients with type 2 diabetes.

Objective: Bile acids have underlying protective effects on bones structure. Long-term diabetes also causes skeletal disorders including osteoporosis, Charcot arthropathy and renal osteodystrophy. Nevertheless, few studies have reported whether bile acid is associated with bone metabolism in diabetics. This study aimed to explore the relationship between total bile acid (TBA) and bone mineral density (BMD) among patients with type 2 diabetes mellitus (T2DM). Methods: We retrospectively included 1,701 T2DM patients who were hospitalized in Taian City Central Hospital (TCCH), Shandong Province, China between January 2017 to December 2019. The participants were classified into the osteopenia (n = 573), osteoporosis (n= 331) and control groups (n= 797) according to BMD in the lumbar spine and femoral. The clinical parameters, including TBA, bilirubin, vitamin D, calcium, phosphorus and alkaline phosphatase were compared between groups. Multiple linear regression was used to analyze the relationship between TBA and BMD in lumbar spine, femoral, trochiter, ward's triangle region. A logistic regression was conducted to develop a TBA-based diagnostic model for differentiating abnormal bone metabolism from those with normal BMD. We evaluated the performance of model using ROC curves. Results: The TBA level was significantly higher in patients with osteoporosis (Median[M]= 3.300 µmol/L, interquartile range [IQR] = 1.725 to 5.250 µmol/L) compared to the osteopenia group (M = 3.200 µmol/L, IQR = 2.100 to 5.400 µmol/L) and control group (M = 2.750 µmol/L, IQR = 1.800 to 4.600 µmol/L) (P <0.05). Overall and subgroup analyses indicated that TBA was negatively associated with BMD after adjusted for the co-variates (i.e., age, gender, diabetes duration, BMI, total bilirubin, direct bilirubin, indirect bilirubin) (P <0.05). Logistic regression revealed that higher TBA level was associated with increased risk for abnormal bone metabolism (OR = 1.044, 95% CI = 1.005 to 1.083). A TBA-based diagnostic model was established to identify individuals with abnormal bone metabolism (T-score ≤ -1.0). The area under ROC curve (AUC) of 0.767 (95% CI = 0.730 to 0.804). Conclusion: Our findings demonstrated the potential role of bile acids in bone metabolism among T2DM patients. The circulating TBA might be employed as an indicator of abnormal bone metabolism.