Pleckstrin-2 mediates the activation of AKT in prostate cancer and is repressed by androgen receptor.

PI3K-AKT and androgen receptor (AR) pathways are commonly activated in prostate cancers. Their reciprocal regulation makes it difficult to treat advanced prostate cancers. Here, we show that Pleckstrin-2 (PLEK2), a proto-oncoprotein involved in the activation and stabilization of AKT, connects these two pathways. We first provide genetic evidence that Plek2 deficiency largely reverted tumorigenesis in Pten prostate-specific knockout mice. Overexpression of PLEK2 promotes the proliferation and colony formation of prostate cancer cells in vitro. In addition, we found that PLEK2 is negatively regulated by AR. AR transcriptionally represses PLEK2 through binding to the PLEK2 promoter region. Overexpression of AR reduces PLEK2 expression, which inactivates AKT. Conversely, knockdown of AR in prostate cancer cells increases PLEK2 expression and activates the AKT pathway. This reciprocal inhibitory loop can be pharmacologically targeted using the PLEK2 inhibitor. We show that the PLEK2 inhibitor dose-dependently inhibits prostate cancer cell proliferation with the inactivation of AKT. Overall, our study uncovers the critical role of PLEK2 in prostate cancer proliferation and provides the rationale for targeting PLEK2 to treat prostate cancers.

Parvimonas micra-induced prosthetic valve endocarditis: a challenging case report and literature review.

Parvimonas micra, a gram-positive anaerobic bacterium, has garnered increased attention due to its role in infective endocarditis. We present a challenging prosthetic valve endocarditis caused by Parvimonas micra in a patient with a complex cardiac history involving multiple surgeries. The case highlights the difficulties in diagnosis and treatment, emphasizing the importance of advanced diagnostic techniques, including metagenomics next-generation sequencing (mNGS). Additionally, it underscores the need for heightened vigilance regarding oral symptoms and the potential risk of bacteremia in post-valvular surgery patients. This report contributes to a better understanding of Parvimonas micra-associated endocarditis and its unique characteristics.

Targeting mitochondria for ovarian aging: new insights into mechanisms and therapeutic potential.

Ovarian aging is a complex process characterized by a decline in oocyte quantity and quality, directly impacting fertility and overall well-being. Recent researches have identified mitochondria as pivotal players in the aging of ovaries, influencing various hallmarks and pathways governing this intricate process. In this review, we discuss the multifaceted role of mitochondria in determining ovarian fate, and outline the pivotal mechanisms through which mitochondria contribute to ovarian aging. Specifically, we emphasize the potential of targeting mitochondrial dysfunction through innovative therapeutic approaches, including antioxidants, metabolic improvement, biogenesis promotion, mitophagy enhancement, mitochondrial transfer, and traditional Chinese medicine. These strategies hold promise as effective means to mitigate age-related fertility decline and preserve ovarian health. Drawing insights from advanced researches in the field, this review provides a deeper understanding of the intricate interplay between mitochondrial function and ovarian aging, offering valuable perspectives for the development of novel therapeutic interventions aimed at preserving fertility and enhancing overall reproductive health.

Pulsatilla decoction alleviates DSS-induced UC by activating FXR-ASBT pathways to ameliorate disordered bile acids homeostasis.

Ethnopharmacological relevance: Pulsatilla decoction (PD) is a classical prescription for the treatment of ulcerative colitis. Previous studies have demonstrated that the therapeutic efficacy of PD is closely associated with the activation of Farnesoid X receptor (FXR). The activity of FXR is regulated by apical sodium-dependent bile acid transporter (ASBT), and the FXR-ASBT cascade reaction, centered around bile acid receptor FXR, plays a pivotal role in maintaining bile acid metabolic homeostasis to prevent the occurrence and progression of ulcerative colitis (UC). Aim of the study: To elucidate the underlying mechanism by which PD exerts its proteactive effects against Dextran Sulfate Sodium Salt (DSS)-induced ulcerative colitis, focusing on the modulation of FXR and ASBT. Materials and methods: To establish a model of acute ulcerative colitis, BALB/C mice were administered 3.5% DSS in their drinking water for consecutive 7 days. The disease activity index (DAI) was employed to evaluate the clinical symptoms exhibited by each group of mice. Goblet cell expression in colon tissue was assessed using glycogen schiff periodic acid-Schiff (PAS) and alcian blue staining techniques. Inflammatory cytokine expression in serum and colonic tissues was examined through enzyme-linked immunosorbent assay (ELISA). A PCR Array chip was utilized to screen 88 differential genes associated with the FXR-ASBT pathway in UC treatment with PD. Western blotting (WB) analysis was performed to detect protein expression levels of differentially expressed genes in mouse colon tissue. Results: The PD treatment effectively reduced the Disease Activity Index (DAI) score and mitigated colon histopathological damage, while also restoring weight and colon length. Furthermore, it significantly alleviated the severity of ulcerative colitis (UC), regulated inflammation, modulated goblet cell numbers, and restored bile acid balance. Additionally, a PCR Array analysis identified 21 differentially expressed genes involved in the FXR-ASBT pathway. Western blot results demonstrated significant restoration of FXR, GPBAR1, CYP7A1, and FGF15 protein expression levels following PD treatment; moreover, there was an observed tendency towards increased expression levels of ABCB11 and RXRα. Conclusion: The therapeutic efficacy of PD in UC mice is notable, potentially attributed to its modulation of bile acid homeostasis, enhancement of gut barrier function, and attenuation of intestinal inflammation.

Efficacy, safety, and serum cytokine modulation by olopatadine hydrochloride and desloratadine citrate disodium combination therapy in urticaria.

OBJECTIVES: To assess the efficacy, safety, and impact on serum cytokines of olopatadine hydrochloride (OLP) combined with desloratadine citrate disodium (DES) in treating urticaria. METHODS: We retrospectively analyzed 114 urticaria patients treated at the Affiliated Hospital of Xinyang Vocational and Technical College from March 2020 to March 2023. The control group (55 patients) received DES, while the research group (59 patients) received OLP+DES combination therapy. We compared efficacy, safety (including epigastric pain, dry mouth, lethargy, dizziness, and fatigue), changes in serum cytokines (interleukin [IL]-2, IL-4, and interferon [IFN]-γ), symptom resolution (wheal number, wheal size, and itching degree), and 3-month recurrence rates. A univariate analysis was also conducted to identify factors influencing urticaria recurrence. RESULTS: The research group exhibited a significantly higher overall efficacy rate, lower incidence of adverse events, and reduced recurrence rates at 3 months (all P<0.05) compared to the control group. Post-treatment, the research group showed significant increases in IL-2 and IFN-γ levels and reductions in IL-4 levels, wheal number, wheal size, and itching degree (all P<0.05). Factors such as history of drinking/smoking, IL-2 levels, and treatment method were associated with urticaria recurrence (all P<0.05). CONCLUSIONS: The combination of OLP and DES is an effective and safe treatment option for urticaria, significantly improving serum cytokine profiles, alleviating symptoms, and reducing recurrence risk.

Interpretation of the effects of rumen acidosis on the gut microbiota and serum metabolites in calves based on 16S rDNA sequencing and non-target metabolomics.

Introduction: Rumen acidosis is one of the most common diseases in beef cattle. It severely affects the normal development of calves and poses a significant threat to the farming industry. However, the influence of rumen acidosis on the gut microbiota and serum metabolites of calves is currently unclear. Objective: The aim of this study is to investigate the changes in the gut microbiota and serum metabolites in calves after rumen acidosis and analyse the correlation. Methods: Eight calves were selected as the rumen acidosis group, and eight health calves were selected as the healthy group. The faecal gut microbiota and serum metabolites of calves were detected respectively using 16S rDNA high-throughput sequencing and non-target metabolomics. The correlation between gut microbiota and serum metabolites was analyzed by Spearman correlation analysis. Results: Differential analysis of the diversity and composition of gut microbiota between eight male healthy (Health) and eight male rumen acidosis (Disease) calves revealed that rumen acidosis increased the abundance of the gut microbiota in calves. At the phylum level, compared to the Healthy group, the relative abundance of Proteobacteria in the Disease group significantly decreased (P<0.05), while the relative abundance of Desulfobacterota significantly increased in the Disease group (P<0.05). At the genus level, compared to the Disease group, the relative abundance of Alloprevotella, Muribaculaceae, Succinivibrio, Prevotella, Agathobacter and Parabacteroides significantly increased in the Healthy group (P<0.05), while the relative abundance of Christensenellaceae_R-7 and Monoglobus significantly decreased in the Healthy group (P<0.05). Differential analysis results showed the Healthy group had 23 genera with higher abundance, while the Disease group had 47 genera with higher abundance. Serum metabolomics results revealed the differential metabolites associated with rumen acidosis, including nicotinamide, niacin, L-glutamic acid and carnosine, were mainly enriched in the nicotinate and nicotinamide pathway and the histidine pathway. Conclusion: The occurrence of rumen acidosis can induce changes in the gut microbiota of calves, with a significant increase of the Christensenellaceae_R-7 genus and a significant decrease of Prevotella and Succinivibrio genera. In addition, the occurrence of rumen acidosis can also induce changes in serum metabolites including niacin, niacinamide, L-glutamine, and carnosine, which may serve as the diagnostic biomarkers of rumen acidosis of calves.

[Effect of different initial processing treatments on commercial characters and chemical components of Fritillaria taipaiensis].

To investigate the effects of different initial processing methods on the quality of Fritillaria taipaiensis, this study explored the effects of anti-browning treatment, drying methods, and drying temperatures on the commercial characters, chromaticity values, and alkaloid and nucleoside components of Fritillariae Taipaiensis Bulbus. The results were comprehensively evaluated through correlation analysis(CA), principal component analysis(PCA), and hierarchical clustering analysis(HCA). Compared with those of the direct drying group(WD60), the chromaticity values(ΔE*) of the groups with scraped outer skin( FHB1) and mixed lime powder treatments(FHB2) were significantly reduced, indicating the inhibition of the browning process. The total alkaloid content of the group with mixed raw soil treatment(FHB3) and the FHB2 group showed no significant change, whereas that of the group with 5%Na Cl O solution rinse treatment(FHB4) was the lowest. Compared with air-blast dried(WD50) samples, the ΔE* values of freezedried(FS6) and vacuum-dried(FS5) samples were significantly decreased, with an increase in total alkaloid contents. Conversely,the ΔE* values of shade-dried(FS1) and sun-dried(FS2) samples were significantly increased, with severe browning and low total alkaloid contents. The total alkaloid contents of heat-pump-dried(FS4) samples showed no significant change, and their ΔE* value was significantly decreased, with a light degree of browning and favorable commercial characters. The total alkaloid content of air-blast dried samples initially increased and then decreased within the range of 40-80 ℃, and the highest content was recorded at 70 ℃. The ΔE* values of high-temperature air-blast dried samples(70-80 ℃) were smaller with a light degree of browning, whereas their texture was compact and lacked powder. CA revealed a significant relationship between the uracil content and chromaticity value of the samples(P< 0. 05). The clustering relationships among samples subjected to different treatments were visualized via PCA and HCA. The results showed that FHB2 and air-blast drying(50-60 ℃) were more suitable for large-scale production, and heat pump drying could be a promising direction for future development. This study provides a scientific basis for optimizing the initial processing methods of Fritillaria taipaiensis.

Ct-based diagnosis of sarcopenia as a prognostic factor for postoperative mortality after elective open-heart surgery in older patients: a cohort-based systematic review and meta-analysis.

Background: Cardiac open-heart surgery, which usually involves thoracotomy and cardiopulmonary bypass, is associated with a high incidence of postoperative mortality and adverse events. In recent years, sarcopenia, as a common condition in older patients, has been associated with an increased incidence of adverse prognosis. Methods: We conducted a search of databases including PubMed, Embase, and Cochrane, with the search date up to January 1, 2024, to identify all studies related to elective cardiac open-heart surgery in older patients. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Results: A total of 12 cohort studies were included in this meta-analysis for analysis. This meta-analysis revealed that patients with sarcopenia had a higher risk of postoperative mortality. Furthermore, the total length of hospital stay and ICU stay were longer after surgery. Moreover, there was a higher number of patients requiring further healthcare after discharge. Regarding postoperative complications, sarcopenia patients had an increased risk of developing renal failure and stroke. Conclusion: Sarcopenia served as a tool to identify high-risk older patients undergoing elective cardiac open-heart surgery. By identifying this risk factor early on, healthcare professionals took targeted steps to improve perioperative function and made informed clinical decisions.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023426026.

FeNi-LDH COATED WITH ORANGE-PEEL CARBON AEROGEL FOR OXYGEN EVOLUTION REACTION.

In this work, the waste orange-peel was used as carbon source, and the orange-peel derived carbon material can be obtained through simple pyrolysis. Then, we designed the structure of orange-peel carbon aerogel grown on iron-nickel layered double hydroxides in situ to achieve the effect of carbon coating (FeNi-LDH/CA). The oxygen evolution reaction catalytic performance of FeNi-LDH/CA is excellent, far exceeding that of commercial RuO2. In 1 M KOH, the overpotential of FeNi-LDH/CA is only 250 mV (10 mA cm-2), obviously better than that of commercial RuO2 (295 mV). FeNi-LDH/CA shows good cycling stability, and after long-term i-t testing, the performance only decays by 3% after running at 100 mA cm-2 for 100 h. When used as an anode, the voltage of water-splitting is only 1.48 V at 10 mA cm-2. The rechargeable liquid zinc-air battery based on Pt/C-FeNi-LDH/CA catalyst has higher open-circuit voltage (1.543 V) and galvanostatic discharge capacity at 1.23 V (830 min, 10 mA cm-2). Moreover, the zinc-air battery based on Pt/C-FeNi-LDH/CA has a small charge-discharge voltage gap (0.65 V) at 10 mA cm-2, after 200 consecutive cycles (66 h), the charge-discharge voltage gap only increased by about 30 mV, indicating good cycling stability.

Investigation of canopy interception characteristics in slope protection grasses: A laboratory experiment.

Canopy interception significantly affects hydrological processes such as infiltration, runoff and evapotranspiration. Research on grass canopy interception remains limited, and the experimental methods employed differ substantially. To thoroughly investigate the canopy interception characteristics of grass and clarify the methodological differences, five commonly utilized slope protection grass species in temperate regions were cultivated in a laboratory setting, and their canopy interception characteristics were experimentally investigated using the water-balance method (WBM), the water-wiping method (WWM) and the water-immersion method (WIM), respectively. The results showed that the WBM is more accurate for measuring canopy interception in grass, whereas both the WWM and the WIM underestimate grass canopy interception capacity. The canopy interception capacity measured by the WBM was 1.61-2.09 times higher than that of the WWM and 1.93-3.47 times higher than that of the WIM. Grey correlation analysis of the eight evaluated factors indicated that leaf area is the most influential factor affecting canopy interception in grass, followed by rainfall amount, dry mass, rainfall intensity, canopy projection area, leaf contact angle, fresh weight, and average height. There is a negative power function relationship between the interception ratio and the rainfall amount. With increasing rainfall intensity, the canopy interception capacity initially increases and then decreases, peaking at rainfall intensities of 15 to 20 mm/h. Leaf contact angle is a key quantifiable parameter that explains the differences in canopy interception among different grass species, and the canopy interception per unit leaf area decreases as the leaf contact angle increases. This study demonstrates that the WBM provides the most accurate measurements of grass canopy interception compared to the WWM and WIM, and highlights the leaf contact angle as a key factor in explaining interspecies differences. These findings could enhance the understanding of grass canopy interception and guide the selection of experimental methods.

Early changes in corneal densitometry after FS-LASIK combined with accelerated corneal cross-linking for correction of high myopia.

AIM: To observe the effects of femtosecond laser-assisted excimer laser in situ keratomileusis combined with accelerated corneal cross-linking (FS-LASIK Xtra) on corneal densitometry after correcting for high myopia. METHODS: In this prospectively study, 130 patients underwent FS-LASIK or FS-LASIK Xtra for high myopia. Their right eyes were selected for inclusion in the study, of which 65 cases of 65 eyes in the FS-LASIK group, 65 patients with 65 eyes in the FS-LASIK Xtra group. Patients were evaluated for corneal densitometry at 1, 3, and 6mo postoperatively using Pentacam Scheimpflug imaging. RESULTS: Preoperative differences in corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups in different ranges were not statistically significant (P>0.05). Layer-by-layer analysis revealed statistically significant differences in the anterior (120 µm), central, and total layer corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups at 1 and 3mo postoperatively (all P<0.05), the FS-LASIK Xtra group is higher than that of the FS-LASIK group. Analysis of different diameter ranges showed statistically significant differences between the FS-LASIK group and the FS-LASIK Xtra group at 1mo postoperatively in the ranges of 0-2, 2-6, and 6-10 mm (both P<0.05); At 3mo postoperatively, the FS-LASIK Xtra group is higher than that of the FS-LASIK group in the ranges of 0-2 and 2-6 mm (P<0.05). At 6mo postoperatively, there were no statistically significant differences in corneal densitometry between the FS-LASIK group and the FS-LASIK Xtra group in different diameter ranges (all P>0.05). CONCLUSION: There is an increase in internal corneal densitometry during the early postoperative period after FS-LASIK Xtra for correction of high myopia. However, the densitometry values decreased to the level of conventional FS-LASIK at 6mo after surgery, with the most significant changes observed in the superficial central zone.

Numerical Investigation of Funicular Liquid Bridges between Three Spherical Grains in a Bidisperse Particulate System.

Appropriate capillary effects are beneficial for controlling the wet powder performance and agglomerate formation. As water content rises, the funicular regime supplants the pendular regime as the predominant state in wet granular media. The displacement of grains leading to the stretching of funicular liquid bridges until rupture is an interesting and common phenomenon. Utilizing Surface Evolver software (an energy minimization approach), this work develops an efficient and accurate numerical model to describe liquid interactions among three spherical grains. The effects of liquid volume, contact angle, grain size ratio, grain-pair gap, and separation distance on the capillary forces and rupture distances are investigated. Notably, we present a modified closed-form equation for predicting the rupture distance of funicular bridges between three grains, which reflects the coupled effects of the contact angle, grain size, and liquid volume on rupture distance. This present study provides insights for incorporating capillary effects into mechanical models relying on microassembly composed of several grains in bidisperse particulate systems. Additionally, the numerical findings confirm some findings regarding the splitting of funicular bridges.

Research on the mechanism of Guanyu Zhixie Granule in intervening gastric ulcers in rats based on network pharmacology and multi-omics.

Objective: Guanyu Zhixie Granule (GYZXG) is a traditional Chinese medicine compound with definite efficacy in intervening in gastric ulcers (GUs). However, the effect mechanisms on GU are still unclear. This study aimed to explore its mechanism against GU based on amalgamated strategies. Methods: The comprehensive chemical characterization of the active compounds of GYZXG was conducted using UHPLC-Q/TOF-MS. Based on these results, key targets and action mechanisms were predicted through network pharmacology. GU was then induced in rats using anhydrous ethanol (1 mL/200 g). The intervention effects of GYZXG on GU were evaluated by measuring the inhibition rate of GU, conducting HE staining, and assessing the levels of IL-6, TNF-α, IL-10, IL-4, Pepsin (PP), and epidermal growth factor (EGF). Real-time quantitative PCR (RT-qPCR) was used to verify the mRNA levels of key targets and pathways. Metabolomics, combined with 16S rRNA sequencing, was used to investigate and confirm the action mechanism of GYZXG on GU. The correlation analysis between differential gut microbiota and differential metabolites was conducted using the spearman method. Results: For the first time, the results showed that nine active ingredients and sixteen targets were confirmed to intervene in GU when using GYZXG. Compared with the model group, GYZXG was found to increase the ulcer inhibition rate in the GYZXG-M group (p < 0.05), reduce the levels of IL-6, TNF-α, PP in gastric tissue, and increase the levels of IL-10, IL-4, and EGF. GYZXG could intervene in GU by regulating serum metabolites such as Glycocholic acid, Epinephrine, Ascorbic acid, and Linoleic acid, and by influencing bile secretion, the HIF-1 signaling pathway, and adipocyte catabolism. Additionally, GYZXG could intervene in GU by altering the gut microbiota diversity and modulating the relative abundance of Bacteroidetes, Bacteroides, Verrucomicrobia, Akkermansia, and Ruminococcus. The differential gut microbiota was strongly associated with serum differential metabolites. KEGG enrichment analysis indicated a significant role of the HIF-1 signaling pathway in GYZXG's intervention on GU. The changes in metabolites within metabolic pathways and the alterations in RELA, HIF1A, and EGF mRNA levels in RT-qPCR experiments provide further confirmation of this result. Conclusion: GYZXG can intervene in GU induced by anhydrous ethanol in rats by regulating gut microbiota and metabolic disorders, providing a theoretical basis for its use in GU intervention.

Research progress in isolation and identification of rumen probiotics.

With the increasing research on the exploitation of rumen microbial resources, rumen probiotics have attracted much attention for their positive contributions in promoting nutrient digestion, inhibiting pathogenic bacteria, and improving production performance. In the past two decades, macrogenomics has provided a rich source of new-generation probiotic candidates, but most of these "dark substances" have not been successfully cultured due to the restrictive growth conditions. However, fueled by high-throughput culture and sorting technologies, it is expected that the potential probiotics in the rumen can be exploited on a large scale, and their potential applications in medicine and agriculture can be explored. In this paper, we review and summarize the classical techniques for isolation and identification of rumen probiotics, introduce the development of droplet-based high-throughput cell culture and single-cell sequencing for microbial culture and identification, and finally introduce promising cultureomics techniques. The aim is to provide technical references for the development of related technologies and microbiological research to promote the further development of the field of rumen microbiology research.

p38 Signaling Mediates Naringin-Induced Osteogenic Differentiation of Porcine Metanephric Mesenchymal Cells.

OBJECTIVE: To explore the potential of metanephric mesenchymal cells (MMCs) for osteogenesis and naringin's ability to enhance this process and its molecular mechanism. METHODS: Porcine MMCs at 70 days of gestation were used as tool cells, cultured in osteogenic induction medium, identified by immunocytochemistry staining. Osteogenic potential of porcine MMCs and naringin's ability to enhance this process was tested by detecting changes in cell viability, alkaline phosphatase (ALP) activity, the expression of runt-related transcription factor 2 (Runx2), osteopontin (OPN) and osteocalcin (OCN), and the formation of mineralized nodules, and the application of the p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin. RESULTS: Immunocytochemical staining showed that the cells were Vimentin and Six2(+), E-cadherin and CK-18(-). Naringin can activate the p38 signaling pathway to enhance the osteogenesis of porcine MMCs by increasing cell viability, ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05). The application of p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin, manifested by decreased ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05). CONCLUSION: Naringin, the active ingredient of Chinese herbal medicine Rhizoma Drynariae for nourishing Shen (Kidney) and strengthening bone, enhances the osteogenic differentiation of renal MMCs through the p38 signaling pathway.

Diagnostic value of carbohydrate antigen 50 in biliary tract cancer: A large-scale multicenter study.

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

Comparing collagenase and silver sulfadiazine in deep second-degree burn treatment.

The indications for collagenase ointment (CO) and its efficacy are not clearly established in the treatment of second-degree burn wounds. To evaluate the efficacy of CO versus silver sulfadiazine ointment (SSD) in the treatment of second-degree burn wounds. A total of 170 eligible patients with deep second-degree burns, aged 18-65 years, with injuries occurring within 48-96 h, and having a total wound area of less than 30% of the total body surface area were included from 5 centers in China. The primary outcome was the wound healing time, and the secondary outcomes were the clearance time of wound necrotic tissues, wound healing rate, and wound inflammation. The study included 85 patients in SSD group and 84 in CO group in the modified intention-to-treat (mITT) population. The median time of wound healing was comparable in both groups (10 days vs. 10.5 days P = 0.16). The time for wound necrotic tissue removal was significantly shortened by CO compared with SSD (5 vs. 10 days P < 0.01). Wound inflammation, pain, wound healing rate, and scar were compared with SSD (all P-values > 0.05). No adverse events, such as infection or allergic reactions to the drugs and materials used, were reported. Both CO and SSD could heal the burn wounds at 10 days of treatment. However, CO significantly shortened the time of wound necrotic tissue removal by 5 days. Trial Registration: ChiCTR2100046971.

Differences in regional brain structure in toddlers with autism are related to future language outcomes.

Language and social symptoms improve with age in some autistic toddlers, but not in others, and such outcome differences are not clearly predictable from clinical scores alone. Here we aim to identify early-age brain alterations in autism that are prognostic of future language ability. Leveraging 372 longitudinal structural MRI scans from 166 autistic toddlers and 109 typical toddlers and controlling for brain size, we find that, compared to typical toddlers, autistic toddlers show differentially larger or thicker temporal and fusiform regions; smaller or thinner inferior frontal lobe and midline structures; larger callosal subregion volume; and smaller cerebellum. Most differences are replicated in an independent cohort of 75 toddlers. These brain alterations improve accuracy for predicting language outcome at 6-month follow-up beyond intake clinical and demographic variables. Temporal, fusiform, and inferior frontal alterations are related to autism symptom severity and cognitive impairments at early intake ages. Among autistic toddlers, brain alterations in social, language and face processing areas enhance the prediction of the child's future language ability.

Changes in PI3K/AKT and NRF2/HO-1 signaling expression and intestinal microbiota in bleomycin-induced pulmonary fibrosis.

Pulmonary fibrosis is the outcome of the prolonged interstitial pneumonia, characterized by excessive accumulation of fibroblasts and collagen deposition, leading to its development. This study aimed to study the changes in PI3K/AKT and NRF2/HO-1 signaling expression and intestinal microbiota in a rat model of a novel bleomycin-induced pulmonary fibrosis. The findings of our study showed the model was successfully established. The results showed that the alveolar septum in the model was significantly widened and infiltrated by severe inflammatory cells. Alveolar atrophy occurred due to the formation of multiple inflammatory foci. During this period, fibrous tissue was distributed in strips and patches, primarily around the pulmonary interstitium and bronchus. Moreover, lung damage and fibrosis progressively worsened over time. The mRNA expression of HO-1 and NRF2 in the model decreased while the mRNA expression of HIF-1α, VEGF, PI3K and AKT increased. Furthermore, it was observed to decrease the protein expression of E-cad, HO-1 and NRF2, and increase the protein expression of α-SMA and p-AKT. Additionally, this model leaded to an imbalance in the intestinal microbiota. This study demonstrate that the novel pulmonary fibrosis model activates the NRF2/HO-1 pathway and the PI3K/AKT pathway in rat lung tissues, and leading to intestinal barrier disorder.