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Background This study aimed to assess and compare procalcitonin (PCT) and C-reactive protein (CRP) levels between COVID-19 and non-COVID-19 sepsis patients. Additionally, we evaluated the diagnostic efficiency of PCT and CRP in distinguishing between Gram-positive (GP) and Gram-negative (GN) bacterial infections. Moreover, we explored the associations of PCT with specific pathogens in this context. Methods The study included 121 consecutive sepsis patients who underwent blood culture testing during the COVID-19 epidemic. PCT and CRP were measured, and reverse transcriptase-polymerase chain reaction (RT-PCR) was employed for the detection of COVID-19 nucleic acid. The Mann-Whitney U-test was used to compare PCT and CRP between the COVID-19 and non-COVID-19 groups. Receiver operating characteristic (ROC) curves were generated to compare PCT and CRP levels in the GN group versus the GP group for assessing the diagnostic efficiency. The kruskal-Wallis H test was applied to assess the impact of specific pathogen groups on PCT concentrations. Results A total of 121 sepsis patients were categorized into a COVID-19 group (n = 25) and a non-COVID-19 group (n = 96). No significant differences in age and gender were observed between the COVID-19 and non-COVID-19 groups. The comparison of biomarkers between these groups showed no statistically significant differences. The optimal cut-off values for PCT and CRP in differentiating between GP and GN infections were 1.03 ng/mL and 34.02 mg/L, respectively. The area under the ROC curve was 0.689 (95% confidence interval (CI) 0.591–0.786) for PCT and 0.611 (95% CI 0.505–0.717) for CRP. The diagnostic accuracy was 69.42% for PCT and 58.69% for CRP. The study found a significant difference in PCT levels among specific groups of pathogens ( P  < 0.001), with the highest levels observed in Escherichia coli infections. The frequency of Staphylococcus spp. positive results was significantly higher (36.0%) in COVID-19 compared to non-COVID-19 sepsis patients ( P  = 0.047). Conclusion Sepsis patients with COVID-19 revealed a significantly higher culture positivity for staphylococcus spp. than the non-COVID-19 group. Both PCT and CRP showed moderate diagnostic efficiency in differentiating between GP and GN bacterial infections. PCT showed potential utility in identifying E. coli infections compared to other pathogens.

is the predominant uropathogen in urinary tract infections (UTIs), but culture-based identification is time-consuming. This study aimed to develop an explainable, culture-independent model to distinguish from other uropathogens using routinely collected clinical data. We retrospectively analyzed 308 hospitalized patients with culture-confirmed UTIs at Fuding Hospital, Fujian University of Traditional Chinese Medicine (January-December 2023), classified as (n = 158) or non- i (n = 150). Species identification was performed using an automated microbiology system. Nineteen predictors (sex, urinary leukocyte grade, and 17 routine laboratory variables) were used. Associations with UTI were examined using univariate and multivariable logistic regression. A Random Forest (RF) classifier was developed with SHapley Additive exPlanations (SHAP) for interpretability. Data were split using a stratified 70/30 train-test split; 5-fold stratified cross-validation within the training set was used for hyperparameter tuning, and final performance (discrimination and calibration) was reported on the held-out test set. RF was additionally benchmarked against regularized logistic regression, calibrated linear SVM, and gradient boosting using the same protocol. accounted for 51.3% of isolates, followed by spp. (18.5%) and spp. (7.8%). Compared with non- cases, infections were more common in females and showed higher lymphocyte counts (LYM), alanine aminotransferase (ALT), and albumin (ALB) (all P < 0.05). Multivariable logistic regression identified sex, LYM, and urinary leukocyte grade as independent predictors. On the held-out test set, RF achieved moderate discrimination (ROC-AUC = 0.66; average precision = 0.66) with calibration assessed by Brier score and calibration slope. SHAP highlighted Sex, LYM, and ALT as the most influential predictors and revealed patient-level heterogeneity in feature effects. remains the predominant pathogen among hospitalized UTIs. An explainable RF model using routine laboratory variables provided moderate, reproducible discrimination of vs non- UTIs and may support earlier decision-making while awaiting culture results.

This study aimed to evaluate the predictive utility of routine hematological, inflammatory, and metabolic markers for bacteremia and to compare the classification performance of logistic regression and random forest models. A retrospective study was conducted on 287 inpatients who underwent blood culture testing at Fuding Hospital, Fujian University of Traditional Chinese Medicine between March and August 2024. Patients were divided into bacteremia (n = 137) and non-bacteremia (n = 150) groups based on blood culture results. Hematological indices, inflammatory markers (e.g., C-reactive protein (CRP), procalcitonin (PCT)), metabolic indices (e.g., glucose, cholesterol) and nutritional markers (e.g., albumin) were analyzed. Univariate and multivariate binary logistic regression analyses were used to identify independent risk factors. Logistic regression and random forest models were developed using 33 features with a 70:30 train-test split and evaluated using the receiver operating characteristic (ROC) curves, confusion matrices and standard classification. Hemoglobin, cholesterol, and albumin levels were significantly lower in the bacteremia group, while platelet count, CRP, PCT, glucose, and triglycerides were significantly elevated (all p < 0.05). Logistic regression identified platelet count (Odds ratios (OR) = 1.003, 95% confidence interval (CI): 1.001-1.006), PCT (OR = 1.032, 95% CI: 1.004-1.060), triglycerides (OR = 1.740, 95% CI: 1.052-2.879), and low cholesterol (OR = 0.523, 95% CI: 0.383-0.714) as independent risk factors. The area under the ROC curve (AUC) was 0.75 for the random forest model and 0.74 for logistic regression, with recall rates of 0.69 and 0.60, respectively. Routine laboratory markers integrated into machine learning models demonstrated potential for early bacteremia prediction. Random forest exhibited superior sensitivity compared to logistic regression, suggesting its potential utility as a clinical screening tool.

Ebolavirus can cause hemorrhagic fever in humans with a mortality rate of 50%-90%. Currently, no approved vaccines and antiviral therapies are available. Human TIM1 is considered as an attachment factor for EBOV, enhancing viral infection through interaction with PS located on the viral envelope. However, reasons under- lying the preferable usage of hTIM-1, but not other PS binding receptors by filovirus, remain unknown. We firstly demonstrated a direct interaction between hTIM-1 and EBOV GP in vitro and determined the crystal structures of the Ig V domains of hTIM-1 and hTIM-4. The binding region in hTIM-1 to EBOV GP was mapped by chimeras and mutation assays, which were designed based on structural analysis. Pseudovirion infection assays performed using hTIM-1 and its homologs as well as point mutants verified the location of the GP binding site and the importance of EBOV GP-hTIM-1 interaction in EBOV cellular entry.

Bone metastasis is a frequent complication of breast cancer and a common cause of morbidity and mortality from the disease. During metastasis secreted proteins play crucial roles in the interactions between cancer cells and host stroma. To characterize the secreted proteins that are associated with breast cancer bone metastasis, we preformed a label-free proteomic analysis to compare the secretomes of four MDA-MB-231 （MDA231） derivative cell lines with varied capacities of bone metastasis. A total of 128 proteins were found to be consistently up-/down-regulated in the conditioned medium of bone-tropic cancer cells. The enriched molecular functions of the altered proteins included receptor binding and peptidase inhibition. Through additional transcriptomic analyses of breast cancer cells, we selected cystatin E/M （CST6）, a cysteine protease inhibitor down-regulated in bone-metastatic cells, for further functional studies. Our results showed that CST6 suppressed the proliferation, colony formation, migration and invasion of breast cancer cells. The suppressive function against cancer cell motility was carried out by cancer cell-derived soluble CST6. More importantly, ectopic expression of CST6 in cancer cells rescued mice from overt osteolytic metastasis and deaths in the animal study, while CST6 knockdown markedly enhanced cancer cell bone metastasis and shortened animal survival. Overall, our study provided a systemic secretome analysis of breast cancer bone tropism and established secreted CST6 as a bonafide suppressor of breast cancer osteolytic metastasis.

ObjectiveTo evaluate the clinical reliability and validity of the Chinese version of the Patient Health Questionnaire-9 (C-PHQ-9) in patients with psoriasis.DesignCross-sectional study.SettingTertiary care centre.ParticipantsPatients with psoriasis who have not been diagnosed with depression (n=148; mean age 43.37±17.46 years; 31.19% female).Primary and secondary outcome measuresThe primary outcome measures considered in this study were the C-PHQ-9 and the Hamilton Depression Scale (HAMD). The American Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V) was used as the gold standard for the diagnosis of depression. Cronbach’s α and test–retest reliability after 1 week were evaluated using reliability analysis, and criterion and structural validity were assessed using validity analysis. Receiver operating characteristic (ROC) analysis was performed to identify the best demarcation score and diagnostic accuracy.ResultsCompared with DSM-V (27.27%), both C-PHQ-9 (39.19%) and HAMD (31.01%) had higher rates for detecting depression. The mean completion time for C-PHQ-9 evaluation (2.02±0.84 min) was significantly less than that for HAMD (23.37±3.21 min, p<0.001). The Cronbach’s α coefficient for the C-PHQ-9 was 0.938. The correlation coefficients of the nine items with the total scale ranged from 0.540 to 0.854, and the mean inter-item correlation coefficients ranged from 0.376 to 0.933. After a week, the retest coefficient was 0.955 (p<0.01). Principal component factor analysis showed that C-PHQ-9 identified a unifactorial structure. The best cut-off point was 9 points, with a sensitivity of 98.00% and a specificity of 90.80%. The area under the ROC curve was 0.979 (95% CI 0.968 to 0.991).ConclusionC-PHQ-9 has good reliability and validity in patients with psoriasis and can be used for primary screening of patients with psoriasis and depression. This scale has obvious time and labour advantages over the HAMD and should be considered for use in clinical practice.

Smoking tobacco is the major risk factor for developing lung cancer. However, most Han Chinese women with lung cancer are nonsmokers. Chinese cooking methods usually generate various carcinogens in fumes that may inevitably be inhaled by those who cook the food, most of whom are female. We investigated the associations of cooking habits and exposure to cooking fumes with lung cancer among non-smoking Han Chinese women. This study was conducted on 1,302 lung cancer cases and 1,302 matched healthy controls in Taiwan during 2002–2010. Two indices, “cooking time-years” and “fume extractor use ratio,” were developed. The former was used to explore the relationship between cumulative exposure to cooking oil fumes and lung cancer; the latter was used to assess the impact of fume extractor use for different ratio-of-use groups. Using logistic models, we found a dose–response association between cooking fume exposure and lung cancer (odds ratios of 1, 1.63, 1.67, 2.14, and 3.17 across increasing levels of cooking time-years). However, long-term use of a fume extractor in cooking can reduce the risk of lung cancer by about 50%. Furthermore, we provide evidence that cooking habits, involving cooking methods and oil use, are associated with risk of lung cancer.

Obesity and related diseases pose a major health risk, yet current anti-obesity drugs inadequately addressing clinical needs. Here we show AA005, an annonaceous acetogenin mimic, resists obesity induced by high-fat diets and leptin mutations at non-toxic doses, with the alpha subunit of the mitochondrial trifunctional protein (HADHA) as a target identified through proteomics and in vitro validation. Pharmacokinetic analysis shows AA005 enriches in adipose tissue, prompting the creation of adipose-specific Hadha -deficient mice. These mice significantly mitigate diet-induced obesity, echoing AA005’s anti-obesity effects. AA005 treatment and Hadha deletion in adipose tissues increase body temperature and energy expenditure in high-fat diet-fed mice. The beneficial impact of AA005 on obesity mitigation is ineffective without uncoupling protein 1 (UCP1), essential for thermogenesis regulation. Our investigation shows the interaction between AA005 and HADHA in mitochondria, activating the UCP1-mediated thermogenic pathway. This substantiates AA005 as a promising compound for obesity treatment, targeting HADHA specifically. Obesity is a significant health risk, and current treatments are inadequate. This study reveals that AA005, an annonaceous acetogenin mimic, targets mitochondrial HADHA in adipose tissue to boost thermogenesis via the UCP1 pathway, providing a promising new strategy for obesity treatment.

Price is a pivotal determinant of market demand, as higher prices typically reduce sales while lower prices stimulate them. Thus, incorporating price-dependent demand into inventory models is both realistic and necessary. In practice, limited storage capacity often forces retailers to rent additional space, motivating the adoption of two-warehouse systems. Trade credit also plays a critical role in supply chain management: suppliers may offer cash discounts or deferred payments to encourage larger orders, while retailers extend credit to customers to boost sales. To reduce default risk, however, retailers usually provide only partial credit. Considering the time value of money, costs and profits are assessed using discounted cash-flow analysis to account for payment delays and inflation. This study develops an integrated supplier–retailer–customer chain model that (1) incorporates price-dependent demand, (2) includes a rented warehouse for limited storage, (3) considers partial trade credit, (4) links two-level trade credit terms to order quantity, and (5) evaluates financial performance on a present-value basis. The model aims to maximize total profit by determining optimal price, replenishment cycle, and order quantity. Numerical and sensitivity analyses confirm that extending supplier credit can lower prices and improve overall profitability, offering useful insights for strategic inventory management.

Cortex Eucommiae is used worldwide in traditional medicine, various constituents of Cortex Eucommiae, such as chlorogenic acid (CGA), has been reported to exert anti-osteoporosis activity in China, but the mechanism about their contribution to the overall activity is limited. The aims of this study were to determine whether chlorogenic acid can prevent estrogen deficiency-induced osteoporosis and to analyze the mechanism of CGA bioactivity. The effect of CGA on estrogen deficiency-induced osteoporosis was performed in vivo. Sixty female Sprague-Dawley rats were divided randomly among a sham-operated group and five ovariectomy (OVX) plus treatment subgroups: saline vehicle, 17α-ethinylestradiol (E2), or CGA at 9, 27, or 45 mg/kg/d. The rats' femoral metaphyses were evaluated by micro-computed tomography (μCT). The mechanism of CGA bioactivity was investigated in vitro. Bone mesenchymal stem cells (BMSCs) were treated with CGA, with or without phosphoinositide 3-kinase (PI3K) inhibitor LY294002. BMSCs proliferation and osteoblast differentiation were assessed with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and alkaline phosphatase, with or without Shp2 interfering RNA (RNAi). The results display that CGA at 27 and 45 mg/kg/day inhibited the decrease of bone mineral density (BMD) that induced by OVX in femur (p< 0.01), significantly promoted the levels of bone turnover markers, and prevented bone volume fraction (BV/TV), connectivity density (CoonD), trabecular number (Tb.N), trabecular thickness (Tb.Th) (all p< 0.01) to decrease and prevented the trabecular separation (Tb.Sp), structure model index (SMI)(both p< 0.01) to increase. CGA at 1 or 10 μM enhanced BMSC proliferation in a dose-dependent manner. CGA at 0.1 to 10 μM increased phosphorylated Akt (p-Akt) and cyclin D1. These effects were reversed by LY294002. CGA at 1 or 10 μM increased BMSC differentiation to osteoblasts (p< 0.01), Shp2 RNAi suppressed CGA-induced osteoblast differentiation by decreasing Shp2, p-Akt, and cyclin D1. This study found that CGA improved the BMD and trabecular micro-architecture for the OVX-induced osteoporosis. Therefore, CGA might be an effective alternative treatment for postmenopausal osteoporosis. CGA promoted proliferation of osteoblast precursors and osteoblastic differentiation of BMSCs via the Shp2/PI3K/Akt/cyclin D1 pathway.