Whole-volume diffusion kurtosis magnetic resonance (MR) imaging histogram analysis of non-small cell lung cancer: correlation with histopathology and degree of tumor differentiation.

AIMS: To evaluate the role of diffusion kurtosis imaging (DKI) histogram analysis in the characterization of non-small cell lung cancer (NSCLC) and to correlate DKI parameters with tumor cellularity. MATERIALS AND METHODS: Sixty-four patients with pathologically diagnosed NSCLCs were evaluated by DKI on a 3-T scanner. Regions of interest (ROIs) were drawn on the map of b1000 manually. All NSCLCs were histologically graded according to the degree of tumor differentiation. Tumor cellularity was measured by the nuclear-to-cytoplasm (N/C) ratio and the number of tumor cell nuclei (NTCN), the expression of Ki-67 was detected using the streptavidin-peroxidase method. Histogram analysis was performed using voxel-based on raw data from each ROI. RESULTS: NSCLCs were classified as grades 1, 2, and 3 according to differentiation degree. Histogram parameters of apparent diffusion coefficient (ADC) and DKI could discriminate between different grades of tumors (p<0.001). Receiver operating characteristic (ROC) curve analysis showed that Kapp 75th exhibited the best performance with an AUC of 0.936 and sensitivity/specificity of 95.74%/80% (p<0.001) in distinguishing grade 1 from grade 2, ADC mean exhibited the best performance with an AUC of 0.923 and sensitivity/specificity of 92.33%/86.67% (p<0.001) in distinguishing grade 2 from 3. N/C ratio and Ki-67 changed significantly with grade (p<0.01). Negative correlations were found between the ADC mean and the N/C ratio, Ki-67, Dapp mean and N/C ratio, whereas Kapp mean and N/C ratio, Ki-67 were positively correlated. CONCLUSIONS: DKI histogram analysis could quantitatively characterize NSCLC with different grades by probing non-Gaussian diffusion properties related to changes in the tumor microenvironment or tissue complexities in the tumor.

Preoperative prognostic prediction for invasive pulmonary adenocarcinoma: Impact of 18F-FDG PET/CT semi-quantitative parameters associated with new histological subtype classification.

AIMS: To explore the preoperative predictive value of 18F-FDG PET/CT for poor prognostic histologic subtypes of invasive pulmonary adenocarcinoma (IPA) under new classification. MATERIALS AND METHODS: This study included 316 patients. Histopathology of IPA was evaluated by recording the percentage of each histologic component. PET/CT parameters were compared among IPAs with different risks of recurrence. Optimum cutoff values of PET/CT parameters were calculated using ROC curve analysis. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier method, and survival differences between groups were tested using log-rank test. Multivariate analysis for survival was performed using the Cox regression model. RESULTS: Patients were divided into low (LRR), intermediate (IRR), and modified high (mHRR) risk of recurrence group incorporating typical (HRR-T) and nontypical (HRR-NT) subgroups based on histologic patterns. There were significant differences in SUVmax, SUVmean, SUVmin, SUVSD, TLG, and tumor size among three groups. HRR-NT had lower SUVmax, SUVmean, SUVmin, SUVSD and TLG than HRR-T subgroup, and higher SUVmax, SUVmean, SUVmin, SUVSD, MTV, TLG and tumor size than IRR group. ROC curve analysis showed that SUVmax had highest AUC (0.815) in distinguishing LRR and IRR. TLG had highest AUC (0.741) in distinguishing IRR and mHRR. Multivariable analysis showed that tumor size and SUVmax were independent predictors of DFS and OS. CONCLUSIONS: High risk of recurrence of IPA exhibited higher 18F-FDG uptake and tumor size. Tumor size and SUVmax could be used as preoperative surrogates for the IASLC grading system. 18F-FDG PET/CT can improve the preoperative prognostic prediction for IPA patients.

Dietary supplementation of vitamin D3 and calcium partially recover the compromised time budget and circadian rhythm of lying behavior in lactating cows under heat stress.

Heat stress (HS) impedes cattle behavior and performance and is an animal comfort and welfare issue. The objective of this study was to characterize the time budget and circadian rhythm of lying behavior in dairy cows during HS and to assess the effect of dietary supplementation of vitamin D3 and Ca. Twelve multiparous Holstein cows (42.2 ± 5.6 kg milk/d; 83 ± 27 d in milk) housed in tiestalls were used in a split-plot design with the concentration of dietary vitamin E and Se as main plots (LESe: 11.1 IU/kg and 0.55 mg/kg, and HESe: 223 IU/kg and 1.8 mg/kg, respectively). Within each plot cows were randomly assigned to (1) HS with low concentrations of vitamin D3 and Ca (HS, 1,012 IU/kg and 0.73%, respectively), (2) HS with high concentrations of vitamin D3 and Ca (HS+D3/Ca; 3,764 IU/kg and 0.97%, respectively), or (3) thermoneutral pair-fed (TNPF) with low concentrations of vitamin D3 and Ca (1,012 IU/kg and 0.73%, respectively) in a Latin square design with 14-d periods and 7-d washouts. Lying behavior was measured with HOBO Loggers in 15-min intervals. Overall, cows in HS spent less time lying per day relative to TNPF from d 7 to 14. Daily lying time was positively correlated with milk yield, energy-corrected milk yield, and feed efficiency, and was negatively correlated with rectal temperature, respiratory rate, fecal calprotectin, tumor necrosis factor-α, and C-reactive protein. A treatment by time interaction was observed for lying behavior: the time spent lying was lesser for cows in HS than in TNPF in the early morning (0000-0600 h) and in the night (1800-2400 h). The circadian rhythm of lying behavior was characterized by fitting a cosine function of time into linear mixed model. Daily rhythmicity of lying was detected for cows in TNPF and HS+D3/Ca, whereas only a tendency in HS cows was observed. Cows in TNPF had the highest mesor (the average level of diurnal fluctuations; 34.2 min/h) and amplitude (the distance between the peak and mesor; 17.9 min/h). Both the mesor and amplitude were higher in HS+D3/Ca relative to HS (26.6 vs. 25.2 min/h and 3.91 min/h vs. 2.18 min/h, respectively). The acrophase (time of the peak) of lying time in TNPF, HS, and HS+D3/Ca were 0028, 0152, and 0054 h, respectively. Lastly, a continuous increase in daily lying time in TNPF was observed during the first 4 d of the experimental period in which DMI was gradually restricted, suggesting that intake restrictions may shift feeding behavior and introduce biases in the behavior of animals. In conclusion, lying behavior was compromised in dairy cows under HS, characterizing reduced daily lying time and disrupted circadian rhythms, and the compromised lying behavior can be partially restored by supplementation of vitamin D3 and Ca. Further research may be required for a more suitable model to study behavior of cows under HS.

Learning end-to-end respiratory rate prediction of dairy cows from RGB videos.

Respiratory rate (RR) is an important indicator of the health and welfare status of dairy cows. In recent years, progress has been made in monitoring the RR of dairy cows using video data and learning methods. However, existing approaches often involve multiple processing modules, such as region of interest (ROI) detection and tracking, which can introduce errors that propagate through successive steps. The objective of this study was to develop an end-to-end computer vision method to predict RR of dairy cows continuously and automatically. The method leverages the capabilities of a state-of-the-art Transformer model, VideoMAE, which divides video frames into patches as input tokens, enabling the automated selection and featurization of relevant regions, such as a cow's abdomen, for predicting RR. The original encoder of VideoMAE was retained, and a classification head was added on top of it. Further, the weights of the first 11 layers of the pre-trained model were kept, while the weights of the final layer and classifier were fine-tuned using video data collected in a tie-stall barn from 6 dairy cows. Respiratory rates measured using a respiratory belt for individual cows were serving as the ground truth (GT). The evaluation of the developed model was conducted using multiple metrics, including mean absolute error (MAE) of 2.58 breaths per minute (bpm), root mean squared error (RMSE) of 3.52 bpm, root mean squared prediction error (RMSPE; as a proportion of observed mean) of 15.03%, and Pearson correlation (r) of 0.86. Compared with a conventional method involving multiple processing modules, the end-to-end approach performed better in terms of MAE, RMSE and RMSPE. These results suggest the potential to implement the developed computer vision method for an end-to-end solution, for monitoring RR of dairy cows automatically in a tie-stall setting. Future research on integrating this method with other behavioral detection and animal identification algorithms for animal monitoring in a free-stall dairy barn can be beneficial for a broader application.

Exhalomics as a noninvasive method for assessing rumen fermentation in dairy cows: Can exhaled-breath metabolomics replace rumen sampling?

Previously, we used secondary electrospray ionization-mass spectrometry (SESI-MS) to investigate the diurnal patterns and signal intensities of exhaled (EX) volatile fatty acids (VFA) of dairy cows. The current study aimed to validate the potential of an exhalomics approach for evaluating rumen fermentation. The experiment was conducted in a switchback design, with 3 periods of 9 d each, including 7 d for adaptation and 2 d for sampling. Four rumen-cannulated original Swiss Brown (Braunvieh) cows were randomly assigned to 1 of 2 diet sequences (ABA or BAB): (A) low starch (LS; 6.31% starch on a dry matter basis) and (B) high starch (HS; 16.2% starch on a dry matter basis). Feeding was once per day at 0830 h. Exhalome (with the GreenFeed System), and rumen samples were collected 8 times to represent every 3 h of a day, and EX-VFA and ruminal (RM)-VFA were analyzed using SESI-MS and HPLC, respectively. Furthermore, the VFA concentration in the gas phase (HR-VFA) was predicted based on RM-VFA and Henry's Law (HR) constants. No interactions were identified between the types of diets (HS vs. LS) and the measurement methods on daily average VFA profiles (RM vs. EX or HR vs. EX), suggesting a consistent performance among the methods. Additionally, when the 3-h interval VFA data from HS and LS diets were analyzed separately, no interactions were observed between methods and time of day, indicating that the relative daily pattern of VFA molar proportions was similar regardless of the VFA measurement method used. The results revealed that the levels of acetate sharply increased immediately after feeding, trailed by an increase in the acetate:propionate ratio and a steady increase for propionate (2 h after feeding the HS diet, 4 h for LS), and butyrate. This change was more pronounced for the HS diet than the LS diet. However, there was no overall diet effect on the VFA molar proportions, although the measurement methods affected the molar proportions. Furthermore, we observed a strong positive correlation between the levels of RM and EX acetate for both diets (HS: r = 0.84; LS: r = 0.85), RM and EX propionate (r = 0.74), and RM and EX acetate:propionate ratio (r = 0.80). Both EX-VFA and RM-VFA exhibited similar responses to feeding and dietary treatments, suggesting that EX-VFA could serve as a useful proxy for characterizing RM-VFA molar proportions to evaluate rumen fermentation. Similar relationships were observed between RM-VFA and HR-VFA. In conclusion, this study underscores the potential of exhalomics as a reliable approach for assessing rumen fermentation. Moving forward, research should further explore the depth of exhalomics in ruminant studies to provide a comprehensive insight into rumen fermentation metabolites, especially across diverse dietary conditions.

Evaluating GreenFeed and respiration chambers for daily and intraday measurements of enteric gaseous exchange in dairy cows housed in tie-stalls.

The objective of this study was to evaluate the GreenFeed (GF) and respiration chambers (RC) for daily and intraday measurements of the enteric gaseous exchange, as well as the metabolic heat production, lying behavior, and feed intake (FI) rate of dairy cows at these 2 respective housing conditions [tie-stall barn (TS) vs. RC] during the summer periods. Sixteen multiparous lactating dairy cows were recruited and arranged in a randomized complete block design with a baseline period established for each cow. Cows were given a basal diet (CON) for a baseline period of 7 d and were then fed a 3-nitrooxypropanol (3-NOP)-containing feed for the subsequent 26 d as experimental period. During both the baseline and the last 7 d of treatment period, gaseous exchanges of each animal were measured in the TS using GF for 8 6-hourly staggered measurements over 3 d, immediately followed by the measurement in RC for 2 d. Corresponding DMI, milk yield, and behavior parameters (e.g., lying behavior and FI rate) in TS and RC were recorded. The correlation coefficients of CH4 and H2 using raw data were 0.84 and 0.85, respectively. For all gases, correlation coefficients between GF and RC on individual cow level decreased when the marginal fixed effects (e.g., inhibitor and breed) were corrected by a mixed model. There were no differences in daily CH4 production or intensity between GF and RC (442 vs. 443 g CH4/d or 16.6 vs. 16.2 g CH4 /kg MY). However, greater CH4 yield was measured by GF than RC (19.0 vs. 17.8 g CH4/kg DMI), driven by a lower DMI (23.3 vs. 24.6 kg/d) when cows were housed in TS sampled by GF compared with cows being housed and sampled in RC. The correlations for CO2 production and O2 consumption were moderate and expected due to the variation associated with the mild heat stress condition during GF measurements in the TS (Thermal humidity index (THI) 56 vs. 68), as indicated by the reduced lying time (-2.1 h/d). At the intraday level, there was an interaction between techniques and hour-of-day for CH4 production, as indicated by the discrepancies in post-prandial CH4 emissions between techniques. In summary, this set of results showed that there were strong positive correlations for CH4 and H2 emissions between GF and RC based on individual cow data. However, such relationship should be interpreted with caution, given the data clustering resulting from the use of inhibitor 3-NOP. On treatment level, these 2 techniques detected similar inhibitor effect on the estimated daily CH4 emissions. The intraday patterns of CH4 and H2 production captured by GF provided a close approximation for those measured by RC. Nevertheless, potential underestimation may occur, especially following fresh feed delivery. For measuring CO2 production and O2 consumption, the GF captured similar intraday variations to those in the RC. However, the estimated daily production and consumption were not directly comparable, which was expected due to the variable thermal conditions during the summer. Further evaluations under the same weather conditions are warranted.

Effects of 3-nitrooxypropanol (Bovaer10) and whole cottonseed on milk production and enteric methane emissions from dairy cows under Swiss management conditions.

The objective of this study was to determine the potential effect and interaction of 3-nitrooxypropanol (3-NOP; Bovaer, DSM-Firmenich Nutrition Products Ltd.) and whole cottonseed (WCS) on lactational performance and enteric methane (CH4) emission of dairy cows. A total of 16 multiparous cows, including 8 Holstein Friesian (HF) and 8 Brown Swiss (BS; 224 ± 36 DIM, 26 ± 3.7 kg milk yield, mean ± SD), were used in a split-plot design, where the main plot was the breed of cows. Within each subplot, cows were randomly assigned to a treatment sequence in a replicated 4 × 4 Latin square design with 2 × 2 factorial arrangements of treatments with four 24-d periods. The experimental treatments were as follows: (1) control (basal TMR), (2) 3-NOP (60 mg/kg TMR DM), (3) WCS (5% TMR DM), and (4) 3-NOP + WCS. The treatment diets were balanced for ether extract, crude protein, and NDF contents (4%, 16%, and 43% of TMR DM, respectively). The basal diets were fed twice daily at 0800 and 1800 h. Dry matter intake and milk yield were measured daily, and enteric gas emissions were measured (using the GreenFeed System, C-Lock Inc.) during the last 3 d of each 24-d experimental period when animals were housed in tiestalls. There was no difference in DMI on treatment level, whereas the WCS treatment increased ECM yield and milk fat yield. No interaction of 3-NOP and WCS occurred for any of the enteric gas emission parameters, but 3-NOP decreased CH4 production (g/d), CH4 yield (g/kg DMI), and CH4 intensity (g/kg ECM) by 13%, 14%, and 13%, respectively. Further, an unexpected interaction of breed by 3-NOP was observed for different enteric CH4 emission metrics: HF cows had a greater CH4 mitigation effect compared with BS cows for CH4 production (g/d; 18% vs. 8%), CH4 intensity (g/kg milk yield; 19% vs. 3%), and CH4 intensity (g/kg ECM; 19% vs. 4%). Hydrogen production was increased by 2.85-fold in HF and 1.53-fold in BS cows receiving 3-NOP. Further, a 3-NOP × time interaction occurred for both breeds. In BS cows, 3-NOP tended to reduce CH4 production by 18% at approximately 4 h after morning feeding, but no effect was observed at other time points. In HF cows, the greatest mitigation effect of 3-NOP (29.6%) was observed immediately after morning feeding, and it persisted at around 23% to 26% for 10 h until the second feed provision, and 3 h thereafter, in the evening. In conclusion, supplementing 3-NOP at 60 mg/kg DM to a high-fiber diet resulted in 18% to 19% reduction in enteric CH4 emission in Swiss HF cows. The lower response to 3-NOP by BS cows was unexpected and has not been observed in other studies. These results should be interpreted with caution due to the low number of cows per breed. Finally, supplementing WCS at 5% of DM improved ECM and milk fat yield but did not enhance the CH4 inhibition effect of 3-NOP of dairy cows.

Burden of gastrointestinal cancers among people younger than 50 years in China, 1990 to 2019.

OBJECTIVES: This study aimed to assess the burden of early-onset gastrointestinal (GI) cancers in China over three decades. STUDY DESIGN: A comprehensive analysis was performed using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: Data on early-onset GI cancers in 2020 and from 1990 to 2019 were extracted from GLOBOCAN 2020 database and GBD 2019, respectively. The average annual percent change (AAPC) was calculated to analyze the temporal trends using the Joinpoint Regression Program. The Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2030. RESULTS: In China, there were 185,980 incident cases and 119,116 deaths of early-onset GI cancer in 2020, with the highest incidence and mortality observed in liver cancer (new cases: 71,662; deaths: 62,412). The spectrum of early-onset GI cancers in China has transitioned over the last 30 years. The age-standardized rates of incidence, mortality, and disability-adjusted life years for colorectal and pancreatic cancers exhibited rapid increases (AAPC >0, P ≤ 0.001). The fastest-growing incidence rate was found in colorectal cancer (AAPC: 3.06, P < 0.001). Despite the decreases in liver, gastric, and esophageal cancers, these trends have been reversed or flattened in recent years. High body mass index was found to be the fastest-growing risk factor for early-onset GI cancers (estimated annual percentage change: 2.75-4.19, P < 0.05). Projection analyses showed an increasing trend in age-standardized incidence rates for almost all early-onset GI cancers during 2020-2030. CONCLUSIONS: The transitioning pattern of early-onset GI cancers in China emphasizes the urgency of addressing this public health challenge.

Blood transcriptomics reveal systemic eosinophilic and neutrophilic inflammation patterns in patients with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic sinonasal disease characterized by heterogeneous inflammation. However, the presence of systemic inflammation heterogeneity in CRSwNP patients remains unknown. This study aims to profile transcriptomic alterations in the blood of CRSwNP patients and characterize the CRSwNP heterogeneity based on blood transcriptomic biomarkers. METHODOLOGY: Patients with CRSwNP were prospectively recruited from three hospitals and chronologically divided into exploratory (n=123) and independent validation (n=46) cohorts. Transcriptomic profiles were generated by whole blood mRNA sequencing and subjected to patient clustering, differential expression, and pathway analysis. Differences in immune pattern and clinicopathologic features between clusters were assessed. A transcriptomic signature was defined and applied to an independent cohort to validate the findings. RESULTS: CRSwNP patients showed diverse blood transcriptomic profiles versus healthy controls, or when stratified by tissue and blood eosinophils and asthma comorbidity. Transcriptome-wide correlation analysis revealed a transcriptional signature associated with blood eosinophil levels, consisting of nine T2-related genes (CLC, SIGLEC8, ALOX15, IL5RA, PTGDR2, CCL23, CCR3, EPX and IL1RL1). Three distinct clusters with differing systemic eosinophilic and neutrophilic inflammation patterns and asthma comorbidity were identified based on transcriptomic profiling of T2 and T1/3-related blood biomarkers. A 36-gene signature was developed by machine learning and accurately predicted the three CRSwNP subtypes. Validation on an independent cohort confirmed the prediction robustness. CONCLUSIONS: There is heterogeneous systemic inflammation associated with eosinophilic and neutrophilic patterns in patients with CRSwNP. Endotyping based on blood transcriptomic biomarkers might lead to more personalized treatment strategies for CRSwNP in the future.

[Antitumor effects of redox-responsive nanoparticles containing platinum（⠣）in ovarian cancer].

Objectives: To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)-NP@Pt(Ⅳ) in ovarian cancer. Methods: Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)-Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured. Results: The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment (P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 µmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 µmol/L) and cisplatin (5.21, 11.85, and 71.98 µmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm3, which was significantly lower than those in control group [(1 349±161) mm3, P<0.001] and cisplatin group [(715±293) mm3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion: Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

[The predictive value of dynamic changes of neutrophil/lymphocyte ratio (NLR) combined with the model of end-stage liver disease (MELD) score in patients with acute-on-chronic hepatitis B liver failure].

Objective: To determine the predictive value of dynamic changes of neutrophil/lymphocyte ratio (NLR) combined with the model of end-stage liver disease (MELD) score in patients with acute-on-chronic hepatitis B liver failure. Methods: Patients with acute-on-chronic hepatitis B liver failure who were hospitalized in the Department of Hepatology of Qilu Hospital of Shandong University from January 2010 to July 2023 were retrospectively enrolled. According to the clinical outcomes of patients within 30 days of admission, they were divided into the survival group and the death group. The dynamic changes in NLR and initial values on day 3, 5, 8, and 12 in two groups were analyzed for the diagnostic value of 30-day prognosis in patients with acute-on-chronic hepatitis B liver failure. Logistic regression analysis and machine learning XGBoost algorithm were used to evaluate the risk factors influencing the prognosis of patients at 30 days. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of NLR and initial value change combined with MELD score on day 12 of admission in patients with chronic acute hepatitis B liver failure. Results: A total of 243 patients were enrolled in the study, including 145 patients in the survival group [115 males, 30 females, aged 25-74 (47±11)] and 98 patients in the death group [80 males, 18 females, aged 22-80 (49±13) ]. The median initial NLR of survival group and death group were 3.5 (2.1, 5.3) and 4.9 (2.9, 8.3), respectively, and the difference was statistically significant (P=0.003). The variation of NLR from the initial value on day 3, 5, 8, and 12 in the survival group [1.6 (0, 4.3), 1.9 (-0.2, 4.1), 2.0 (-0.1, 4.3) and 2.9 (0.3, 7.0), respectively] were lower than that in the death group [3.2 (0.9, 7.5), 5.1 (1.8, 7.6), 5.8 (2.0, 10.6) and 9.6 (3.5, 16.4), respectively] (all P<0.001). Logistic regression multivariate analysis showed that the changes in NLR on the 12th day and initial value (OR=1.07,95%CI:1.01-1.14, P=0.014), the changes in NLR on the 3rd day and initial value (OR=2.71, 95%CI: 1.32-5.55, P=0.007), the initial value of NLR (OR=1.18,95%CI:1.01-1.37,P=0.035) and fibrinogen (OR=0.21,95%CI:0.05-0.96,P=0.044) were related factors for death within 30 days. Machine learning XGBoost algorithm showed that the weight of the change between the NLR on the 12th day and the initial value was the highest. The area under the ROC curve of the combined MELD score was 0.812 (95%CI: 0.728-0.895), the specificity was 67.78%, and the sensitivity was 82.35%. Conclusion: Dynamic change of NLR combined with MELD score has high predictive value for the short-term prognosis of patients with acute-on-chronic hepatitis B liver failure.

[Role of intercellular adhesion molecule-1 in adhesion and migration of mesenchymal stem cells in ankylosing spondylitis and its mechanisms].

Objective: To investigate the role and underlying mechanisms of intercellular adhesion molecule-1 (ICAM-1) in the adhesion and migration of mesenchymal stem cells (MSCs) in patients with ankylosing spondylitis (AS). Methods: Bone marrow and ligament tissues were collected during surgery from patients with AS and thoracolumbar fractures (as controls, HC) treated from October 2021 to October 2022 at Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital. MSCs were isolated and cultured from the bone marrow using the Ficoll separation method. Cell morphology was observed under high-resolution microscopy, and differences in the cytoskeletal features between AS-and HC-MSCs were analyzed through immunofluorescence staining. The expression of ICAM-1 was quantified in both groups using real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry. Transwell migration assays and wound healing experiments were conducted to evaluate the differences in migration rates between the two groups of MSCs. Results: The interspinous ligament and bone marrow was acquired in AS (2 males and 1 female; 33, 37, 32 years old, respectively) and no-AS patients (2 males and 1 female; 35, 32, 38 years old, respectively). AS-MSCs exhibited broader cell morphology compared to HC-MSCs under bright field and fluorescence microscopy. Immunofluorescence staining of the interspinous ligament showed higher expression of ICAM-1 (68.38±3.42 vs 48.31±2.43) and CD105 (37.97±2.16 vs 23.36±2.06) in AS patients (both P<0.001). Western blot and RT-qPCR analysis revealed significantly stronger protein expression and transcription levels of ICAM-1 in AS-MSCs when compared to those in HC-MSCs (both P<0.001). Flow cytometry confirmed greater mean fluorescence intensity of ICAM-1 in AS-MSCs than in that in HC-MSCs (924.30±54.99 vs 636.47±40.03, P=0.002). Regarding cell adhesion efficiency, it showed no significant difference between AS-MSCs and HC-MSCs in the early stage of adhesion (0.5 h: 1 496±213 vs 1 205±163, P=0.133), but they were all significantly higher in AS-MSCs in the later stage (1 h: 2 894±172 vs 1 908±155, P=0.002; 2 h: 4 540±286 vs 3 334±188, P=0.004; 3 h: 5 212±281 vs 4 208±303, P=0.014). Finally, cell migration experiments demonstrated a stronger migration capability of AS-MSCs compared to HC-MSCs (5 449±172 vs 4 016±155, P<0.001), and the inhibition efficiency of A-205804 on the migration rate of AS-MSCs was stronger than that on HC-MSCs (2 145±239 vs 3 539±316, P=0.004). Conclusions: The aberrant expression of ICAM-1 markedly influences the adhesion and migration dynamics of MSCs. Elevated ICAM-1 levels in MSCs derives from patients with AS significantly enhance their migratory capabilities.

[Goods syndrome in chronic active SARS-CoV-2 infection: a case report].

A 54-year-old female patient presented with recurrent cough and sputum production over the past year and was hospitalized several times. CT examination revealed exudative lesions in both lungs, which were partially absorbed after treatment. However, they recurred shortly after discharge, and the patient had to be readmitted. In the past year, the patient had been hospitalized six times, and her throat swabs were positive for SARS-CoV-2 at four different points in time. After receiving anti-infective and antiviral treatment in other hospitals, the above symptoms were relieved. The patient tested negative for SARS-CoV-2, but symptoms recurred soon after. Eventually, the diagnosis of Goods syndrome was made based on the presence of B-cell loss, decreased immunoglobulin levels, an inverted CD4+/CD8+ ratio on admission, and a previous history of thymoma.

[Surgical treatment and prognosis analysis of hilar cholangiocarcinoma].

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of (M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) µmol/L(range: 5.4 to 722.8 µmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 µmol/L to 85.5 µmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ (P=0.009), hemi-hepatectomy and extended resection (P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1:OR=1.43 (0.61-3.35),P=0.413;T3 vs. T1:OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

[Clinical application of split liver transplantation: a single center report of 203 cases].

Objective: To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application. Methods: This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis. Results: The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group (χ2=5.560,P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group (χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion: SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Clinical utility of repeat fetal echocardiography in congenital heart disease.

OBJECTIVES: To investigate the utility of repeat fetal echocardiography (FE) following a diagnosis of structural congenital heart disease (CHD) on the initial FE. We evaluated how often changes in management and counseling occurred based on subsequent FE findings and sought to determine which types of CHD were more likely to have changes in management and/or counseling based on repeat FE. METHODS: This was a retrospective review of all patients who presented to our center between January 2012 and January 2019 and who had more than one FE performed for structural CHD. We reviewed consultation notes to determine whether management or counseling had changed based on FE findings at follow-up visits. Management variables included a change in location or mode of delivery, plan for atrial septostomy, initiation of prostaglandin infusion, umbilical line placement and planned admission location (nursery vs neonatal intensive care unit). We defined a counseling change as any of the above changes in management as well as any meaningful refinements in the cardiac diagnosis that led to a change in the overall prognosis or future management. Initial diagnoses were grouped into anatomically/hemodynamically relevant subgroups. Fisher's exact test was used to assess the relationship between the initial diagnosis and changes in management. Post-hoc pairwise comparisons were performed using Dunnett's test. RESULTS: Between January 2012 and January 2019, 267 patients underwent 534 follow-up FE assessments performed for structural CHD. Management change based on repeat FE occurred in 41/267 (15.4%) cases. A change in management was associated with the diagnosis made at the initial visit (P < 0.001). The proportion of cases with a management change was highest among those with an initial diagnosis of pulmonary valve abnormality/non-critical pulmonary stenosis (4/11 (36.4%)), followed by balanced atrioventricular canal (AVC) defect (5/17 (29.4%)) and left ventricular outflow tract obstruction/aortic valve abnormality or coarctation/interrupted aortic arch (19/68 (27.9%)). No management change occurred in fetuses diagnosed with isolated ventricular septal defect (VSD), truncus arteriosus, pulmonary vein anomaly or isolated arch sidedness/branching abnormality. Compared to those with a VSD, management was significantly more likely to be changed in fetuses with a balanced AVC defect (P = 0.025) and left heart lesions (P = 0.002). Right heart lesions showed a trend towards an increased incidence of management change (P = 0.05). A counseling change based on repeat FE occurred in 108/267 (40.4%) cases. The proportion of cases with a counseling change was highest among those with an initial diagnosis of pulmonary valve abnormality/non-critical pulmonary stenosis (8/11 (72.7%)) and hypoplastic left heart syndrome/critical aortic stenosis (5/9 (55.6%)). CONCLUSIONS: The clinical utility of follow-up FE is associated with the type of CHD diagnosed. Follow-up FE led to changes in management in several types of CHD, most commonly in cases with an initial diagnosis of right and left outflow obstructive lesions and balanced AVC defect. When developing programmatic protocols for the frequency of FE assessments, the type of CHD should be a major determinant, but additional studies are required to reach a consensus on how often serial FE should be performed for each type of CHD. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

MRI-based radiomics analysis of bladder cancer: prediction of pathological grade and histological variant.

AIM: To develop magnetic resonance imaging (MRI)-based radiomics models for the prediction of the pathological grade and histological variant of bladder cancer. MATERIALS AND METHODS: A total of 227 patients who underwent bladder MRI and had histopathologically confirmed grades and variants were included retrospectively from January 2017 to March 2022. They were assigned to a training set (n=131) and a testing set (n=96) based on the MRI system. MRI-based radiomics features were extracted from manually segmented volumes of interest from high-b-value DWI images and ADC maps. The radiomics models were trained with all possible pipelines in the training set. One optimal model was selected using the fivefold cross-validation method and verified by the testing set according to the pathological results. Univariate and multivariate analyses were performed to identify the significant clinical and imaging factors for developing clinical-radiomics models. RESULTS: The radiomics model for grade prediction had area under the curve (AUC) values of 0.784, 0.786, and 0.733 in the training, cross-validation, and testing sets, respectively. The radiomics model for variant prediction had AUC values of 0.748, 0.757, and 0.789 in the training, cross-validation, and testing sets, respectively. The performance of the clinical-radiomics model was significantly improved compared with the radiomics models alone for the total dataset (AUC for grade: 0.846 versus 0.756; AUC for variant: 0.810 versus 0.757, p<0.05). CONCLUSION: MRI-based radiomics models could be used to predict the pathological grade and histological variants of bladder cancer with relatively good performance.

Threshold of 25(OH)D and consequently adjusted parathyroid hormone reference intervals: data mining for relationship between vitamin D and parathyroid hormone.

PURPOSE: By recruiting reference population, we aimed to (1): estimate the 25(OH)D threshold that maximally inhibits the PTH, which can be defined as the cutoff value for vitamin D sufficiency; (2) establish the PTH reference interval (RI) in population with sufficient vitamin D. METHODS: Study data were retrieved from LIS (Laboratory Information Management System) under literature suggested criteria, and outliers were excluded using Tukey fence method. Locally weighted regression (LOESS) and segmented regression (SR) were conducted to estimate the threshold of 25(OH)D. Multivariate linear regression was performed to evaluate the associations between PTH concentration and variables including 25(OH)D, gender, age, estimated glomerular filtration rate (EGFR), body mass index (BMI), albumin-adjusted serum calcium (aCa), serum phosphate(P), serum magnesium(Mg), and blood collection season. Z test was adopted to evaluate whether the reference interval should be stratified by determinants such as age and gender. RESULTS: A total of 64,979 apparently healthy subjects were recruited in this study, with median (Q1, Q3) 25(OH)D of 45.33 (36.15, 57.50) nmol/L and median (Q1, Q3) PTH of 42.19 (34.24, 52.20) ng/L. The segmented regression determined the 25(OH)D threshold of 55 nmol/L above which PTH would somewhat plateau and of 22 nmol/L below which PTH would rise steeply. Multivariate linear regression suggested that gender, EGFR, and BMI were independently associated with PTH concentrations. The PTH RI was calculated as 22.17-72.72 ng/L for subjects with 25(OH)D ≥ 55 nmol/L with no necessity of stratification according to gender, age, menopausal status nor season. CONCLUSION: This study reported 25(OH)D thresholds of vitamin D sufficiency at 55 nmol/L and vitamin D deficiency at 22 nmol/L, and consequently established PTH RIs in subjects with sufficient vitamin D for northern China population for the first time.

Exhaled volatile fatty acids, ruminal methane emission, and their diurnal patterns in lactating dairy cows.

To date, the commonly used methods to assess rumen fermentation are invasive. Exhaled breath contains hundreds of volatile organic compounds (VOC) that can reflect animal physiological processes. In the present study, for the first time, we aimed to use a noninvasive metabolomics approach based on high-resolution mass spectrometry to identify rumen fermentation parameters in dairy cows. Enteric methane (CH4) production from 7 lactating cows was measured 8 times over 3 consecutive days using the GreenFeed system (C-Lock Technology Inc.). Simultaneously, exhalome samples were collected in Tedlar gas sampling bags and analyzed offline using a secondary electrospray ionization high-resolution mass spectrometry system. In total, 1,298 features were detected, among them targeted exhaled volatile fatty acids (eVFA; i.e., acetate, propionate, butyrate), which were putatively annotated using their exact mass-to-charge ratio. The intensity of eVFA, in particular acetate, increased immediately after feeding and followed a similar pattern to that observed for ruminal CH4 production. The average total eVFA concentration was 35.5 count per second (CPS), and among the individual eVFA, acetate had the greatest concentration, averaging 21.3 CPS, followed by propionate at 11.5 CPS, and butyrate at 2.67 CPS. Further, exhaled acetate was on average the most abundant of the individual eVFA at around 59.3%, followed by 32.5 and 7.9% of the total eVFA for propionate and butyrate, respectively. This corresponds well with the previously reported proportions of these VFA in the rumen. The diurnal patterns of ruminal CH4 emission and individual eVFA were characterized using a linear mixed model with cosine function fit. The model characterized similar diurnal patterns for eVFA and ruminal CH4 and H2 production. Regarding the diurnal patterns of eVFA, the phase (time of peak) of butyrate occurred first, followed by that of acetate and propionate. Importantly, the phase of total eVFA occurred around 1 h before that of ruminal CH4. This corresponds well with existing data on the relationship between rumen VFA production and CH4 formation. Results from the present study revealed a great potential to assess the rumen fermentation of dairy cows using exhaled metabolites as a noninvasive proxy for rumen VFA. Further validation, with comparisons to rumen fluid, and establishment of the proposed method are required.

The impact of social media on guideline-concordant cervical cancer-screening: insights from a national survey.

OBJECTIVES: Cervical cancer is one of the leading causes of cancer mortality in women, yet routine screenings lead to early detection and sometimes even prevention. Screening is an effective way to prevent cervical cancer, and it has been implemented in many countries and regions worldwide, especially in developed countries. However, the incidence of cervical cancer remains a public health problem due to screening disparities in the population. Social media engagement and overloading of online health information may be the cause of this disparity. STUDY DESIGN: Cross-sectional study. METHODS: Data from the Health Information National Trends Survey (a national survey conducted by the National Cancer Institute) was used to characterise cervical cancer screening into two dimensions; namely, high-frequency screening and guideline-concordant screening. The differences between these two screening frequency behaviours were compared by applying ordered logistic regression and binary logistic regression, and the mechanisms of guideline-concordant screening were explored. RESULTS: The factors influencing high-frequency screening and guideline-concordant screening were different. Only self-efficacy (odds ratio [OR] = 1.16; 95% confidence interval [CI] = 0.98, 1.37) had a significant positive association with the high-frequency screening behaviour. Social media engagement (OR = 0.57; 95% CI = 0.33, 0.96) was shown to have a significant negative impact on guideline-concordant screening. A theory-based mechanism of screening behaviour found that traditional health perception factors no longer influence guideline-concordant screening behaviour, whereas environmental factors (e.g., social media) significantly reduce guideline-concordant screening behaviour. CONCLUSIONS: The results from this study indicate that while the internet has become the main channel through which women acquire health resources, and social media has become a main platform for people to obtain health information, online information cannot guide people to engage in appropriate healthy behaviours. Overloading of online health information and the digital divide may lead to excessive screening. Consequently, it is important to address the screening disparity caused by health behaviours as a result of environmental factors and the digital divide.