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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers especially at advanced stage. In order to analyze the dynamics of potential prognostic biomarkers and further quantify their relationships with the overall survival (OS) of advanced PDAC patients, we herein developed a parametric time-to-event (TTE) model integrated with longitudinal submodels. Data from 104 patients receiving standard chemotherapies were retrospectively collected for model development, and other 54 patients were enrolled as external validation. The longitudinal submodels were developed with the time-course data of sum of longest diameters (SLD) of tumors, serum albumin (ALB) and body weight (BW) using nonlinear mixed effect models. The model-derived metrics including model parameters and individual predictions at different time points were further analyzed in the TTE model, together with other baseline information of patients. A linear growth-exponential shrinkage model was employed to describe the dynamics of SLD, while logistic models were used to fit the relationship of time prior to death with ALB and BW. The TTE model estimated the ALB and BW changes at the 9th week after chemotherapies as well as the baseline CA19-9 level that showed most significant impact on the OS, and the model-based simulations could provide individual survival rate predictions for patients with different prognostic factors. This study quantitatively demonstrates the importance of physical status and baseline disease for the OS of advanced PDAC patients, and highlights that timely nutrition support would be helpful to improve the prognosis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

MHC-I-mediated antigen presentation is pivotal in antitumor immunity, enabling the recognition and destruction of tumor cells by CD8 + T cells. Both the proteasome and autophagy serve as essential cellular degradation mechanisms that regulate the stability and functionality of MHC-I molecules. In melanoma, modulating the pathways that affect MHC-I antigen presentation is pivotal and can profoundly influence the therapeutic outcomes of immunotherapy. Our initial effort of this study was a screening process to identify natural compounds capable of amplifying MHC-I surface expression on B16 melanoma cells. Utilizing flow cytometry with fluorescently tagged antibodies, we identified tetrandrine (Tet), a bisbenzylisoquinoline alkaloid derived from the root of Stephania tetrandra, as a potent enhancer of MHC-I-mediated antigen presentation in B16 melanoma cells. We demonstrate that tetrandrine (2.5, 5, 7.5 μM) dose-dependently upregulates both surface and total MHC-I protein levels in B16 or A375 melanoma cells by simultaneously inhibiting autophagy and proteasomal activity, two key pathways involved in MHC-I degradation. This dual inhibition stabilizes MHC-I molecules, leading to enhanced tumor antigen presentation and improved recognition by CD8 + T cells. In co-culture systems, tetrandrine treatment increased CD8 + T cell activation and cytotoxicity against melanoma cells, evidenced by elevated IFN-γ secretion and increased tumor cell apoptosis. Administration of tetrandrine (50 mg·kg -1 ·d -1 , i.g., for 15 days) significantly suppressed melanoma growth in mouse models accompanied by increased CD8 + T cell infiltration and activation within the tumor microenvironment. Notably, tetrandrine synergized with anti-PD-1 immune checkpoint therapy, leading to enhanced tumor growth inhibition compared to either treatment alone. We revealed that tetrandrine (7.5 μM) blocked the lysosomal calcium efflux channel TPC2, disrupting lysosomal calcium homeostasis, thus impairing lysosomal acidification and proteasomal activity, thereby stabilizing MHC-I molecules and promoting antigen presentation. These results highlight tetrandrine's unique mechanism of action in enhancing MHC-I-mediated antigen presentation through dual inhibition of autophagic flux and proteasomal degradation. This study underscores tetrandrine's potential as a novel immunomodulatory agent to boost CD8 + T cell-mediated tumor cell eradication and enhance the efficacy of immune checkpoint therapies., Competing Interests: Competing interests: The authors declare no conflict of interest., (© 2025. The Author(s).)

Background: To investigate the association between air pollution and abnormal alanine aminotransferase levels in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs., Methods: This cross-sectional study enrolled 1,275 patients with chronic hepatitis B treated with nucleotide/nucleoside analogs from 2019 to 2022 in Kaohsiung and analyzed the incidence and risk factors for abnormal alanine aminotransferase levels. Daily air pollutant concentrations were estimated for the year prior to enrolment., Results: Abnormal alanine aminotransferase levels were observed in 1,127 patients (88.4%) before treatment with nucleotide/nucleoside analogs (NAs). Logistic regression analysis revealed that the strongest factor associated with abnormal alanine aminotransferase levels was the level of hepatitis B virus DNA (odds ratio/confidence interval: 1.40/1.25-1.57; p<0.001), followed by concentration of particulate matter ≤2.5 µm in diameter (1.05/1.02-1.08; p<0.001) and liver cirrhosis (0.27/0.17-0.42; p<0.001). Among patients without cirrhosis, logistic regression analysis revealed that the strongest factors associated with abnormal alanine aminotransferase levels were the level of hepatitis B virus DNA (odds ratio/confidence interval: 1.52/1.28-1.82; p<0.001) and concentration of particulate matter ≤2.5 µm in diameter (1.06/1.101-1.11; p=0.01). Among patients with cirrhosis, logistic regression analysis revealed that the strongest factor associated with abnormal alanine aminotransferase levels was hepatitis B virus DNA level (odds ratio/confidence interval: 1.28/1.12-1.48; p=0.001)., Conclusion: Higher concentrations of particulate matter ≤2.5 µm in diameter caused elevated baseline alanine aminotransferase levels in patients with chronic hepatitis B receiving nucleotide/nucleoside analog therapy. The impact of particulate matter ≤2.5 µm in diameter on abnormal alanine aminotransferase levels was particularly pronounced in patients without cirrhosis., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2025, the Chinese Medical Association.)

Recent studies have demonstrated that integrating AI into colonoscopy procedures significantly improves the adenoma detection rate (ADR) and reduces the adenoma miss rate (AMR). However, few studies address the critical issue of endoscopist-AI collaboration in real-world settings. Eye-tracking data collection is considered a promising approach to uncovering how endoscopists and AI interact and influence each other during colonoscopy procedures. A common limitation of existing studies is their reliance on retrospective video clips, which fail to capture the dynamic demands of real-time colonoscopy, where endoscopists must simultaneously navigate the colonoscope and identify lesions on the screen. To address this gap, we established a dataset to analyze changes in endoscopists' eye movements during the colonoscopy withdrawal phase. Eye-tracking data was collected from graduate students, nurses, senior endoscopists, and novice endoscopists while they reviewed retrospectively recorded colonoscopy withdrawal videos, both with and without computer-aided detection (CADe) assistance. Furthermore, 80 real-time video segments were prospectively collected during endoscopists' actual colonoscopy withdrawal procedures, comprising 43 segments with CADe assistance and 37 segments without assistance (normal control)., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Regulator of G protein signaling (RGS) proteins participate in tumor formation and metastasis by acting on the α-subunit of heterotrimeric G proteins. The specific effect of RGS, particularly RGS4 , on the progression of gastric cancer (GC) is not yet clear., Aim: To explore the role and underlying mechanisms of action of RGS4 in GC development., Methods: The prognostic significance of RGS4 in GC was analyzed using bioinformatics based public databases and verified by immunohistochemistry and quantitative polymerase chain reaction in 90 patients with GC. Function assays were employed to assess the carcinogenic impact of RGS4 , and the mechanism of its possible influence was detected by western blot analysis. A nude mouse xenograft model was established to study the effects of RGS4 on GC growth in vitro ., Results: RGS4 was highly expressed in GC tissues compared with matched adjacent normal tissues. Elevated RGS4 expression was correlated with increased tumor-node-metastasis stage, increased tumor grade as well as poorer overall survival in patients with GC. Cell experiments demonstrated that RGS4 knockdown suppressed GC cell proliferation, migration and invasion. Similarly, xenograft experiments confirmed that RGS4 silencing significantly inhibited tumor growth. Moreover, RGS4 knockdown resulted in reduced phosphorylation levels of focal adhesion kinase, phosphatidyl-inositol-3-kinase, and protein kinase B, decreased vimentin and N-cadherin, and elevated E-cadherin., Conclusion: High RGS4 expression in GC indicates a worse prognosis and RGS4 is a prognostic marker. RGS4 influences tumor progression via the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study evaluated the effectiveness of intraovarian platelet-rich plasma (PRP) injection in improving ovarian response and embryo quality in IVF patients with poor embryo quality in previous controlled ovarian hyperstimulation (COH) cycles. 74 patients participated, with 30 in the control group and 44 in the PRP group. PRP was injected during the follicular phase for the PRP group. The control group completed two COH cycles, while the PRP group underwent COH cycles before and after the PRP injection. In the first COH cycle, there were no significant differences between groups. However, in the second COH cycle, the PRP group showed significant improvements: the number of fertilized oocytes increased (5.2 ± 3.6 vs. 3.3 ± 3.5, p = 0.011), total blastocysts (1.7 ± 1.5 vs. 0.5 ± 0.7, p < 0.0001) and good quality blastocysts (0.6 ± 0.8 vs. 0 ± 0.2, P < 0.0001). The total blastocyst rate (35 ± 31% vs. 13 ± 24%, p = 0.001) and good quality blastocyst rate (14 ± 22% vs. 1 ± 3%, p < 0.0001) were also higher in the PRP group. The most notable benefits occurred when COH was conducted one to two months post-PRP injection., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The soybean mosaic disease-caused by the soybean mosaic virus (SMV)-significantly impacts soybean quality and yield. Among its various strains, SMV-SC7 is prevalent in China. Therefore, rapid and accurate diagnosis is deemed critical to mitigate the spread of SMV-SC7. In this study, a simple and rapid magnetic bead-based RNA extraction method was optimized. Furthermore, a reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay that requires no specialized equipment such as PCR Amplifier was proposed, employing a lateral flow device (LFD) for visual interpretation of SMV-SC7. The RT-LAMP-LFD approach facilitated specificity testing of SMV-SC7. Moreover, the limit of detection (LOD) of this method was as low as 10 -5 ng (2.4 copies). The sensitivity of RT-LAMP-LFD was 10-fold higher than that of the colorimetric RT-LAMP method. In 194 field samples tested, the RT-LAMP-LFD detection of the SMV-SC7 had accuracy of 98.45% in comparison to RT-qPCR. In conclusion, the assay exhibited high specificity, sensitivity, and rapidity, enabling economical and portable detection of SMV-SC7 and providing technical support to identify SMV-SC7-infected soybeans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Guo, Zhang, Bai, Yue, Niu, Yin, Yue, Du and Zhao.)

Purpose: To assess macular microstructural changes associated with internal limiting membrane peeling (ILMP) using 3-dimensional optical coherence tomography (3D-OCT) in primary macula-off rhegmatogenous retinal detachment (RRD) repairs with vitrectomy and silicone oil (SO) tamponade., Design: Retrospective, consecutive, interventional case series., Methods: Setting: Institutional practice., Patient Population: Patients who received primary RRD repair by a single experienced surgeon between January 2017 and December 2021., Main Outcome Measures: In the qualitative comparative analysis, the presence of macular changes among patients who underwent primary RRD repair with (21 eyes) or without ILMP (20 eyes) were observed. Subsequently, a detailed quantitative analysis of ILMP-related microstructural changes in 56 eyes using both 3D and 2D-OCT images were performed., Results: In the qualitative comparative analysis, macular microstructural changes were observed in 95% of ILMP eyes and 5% of non-ILMP eyes (p < .001). In the quantitative analysis, 4 major macular microstructural changes were detected: dimple (75%), dissociated nerve fiber layer (DONFL) (55%), ILM peeling edge thinning (IPET) (64%), and temporal macular groove (TMG) (23%). Dimples (n = 251, average 4.5 ± 5.8 per eye) could be further classified into type I (confined to the inner plexiform layer [IPL]; 73%) and type II (beyond IPL, 27%). The average depth of the deepest dimples was 58 ± 18 µm. The extent of IPET was 6.0 ± 3.7 clock hours. The average length of TMG was 1.8 ± 0.4 mm. Comparing to unoperated fellow eyes, the eyes after ILMP showed decreased inner temporal over nasal retinal thickness ratio (0.86 ± 0.07 versus 0.96 ± 0.03, p < .001), shorter disc-fovea distance (4.61 ± 0.32 µm versus 4.78 ± 0.37 µm, p = .041), and wider retinal vein trajectories (c' = 2.48 ± 0.84 vs 3.39 ± 1.61, p = .002)., Conclusions: Macular microstructural changes are common after ILMP in RRD repair, encompassing both focal changes (dimples, DONFL) and zonal changes (IPET, TMG). DONFL and dimples may be part of a continuum of findings stemming from the same mechanism. IPET and TMG are the results of macular tissue shift due to contracture of the optic disc and neurovascular bundle., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Survival is one of the foremost endpoints in cancer therapy, and parametric survival analysis could comprehensively demonstrate the overall result of various different baseline and longitudinal factors. In this study, the survival of triple negative breast cancer 4T1 tumor-bearing mice treated by gemcitabine (GEM) and dexamethasone (DEX) was investigated with model-based analysis. The tumor size, lymphocyte (LY) and neutrophil (NE) of 4T1 tumor-bearing BALB/c mice were collected, and the PK/PD models of these longitudinal data were established in a sequential manner, respectively. The parametric time-to-event (TTE) model of survival was developed and the PK/PD models were tested and integrated as time-varying prognostic factors. The final model was evaluated and externally validated. LY and NE influence the survival directly, while tumor size showed its indirect impact on survival by affecting LY. The exposure of GEM significantly improved the survival results but DEX did not bring extra benefit. The models established in this study quantitatively characterized the abnormal increasing of LY and NE due to tumor progression in T1 tumor-bearing mice and also demonstrate their relationship with survival outcomes, and further provide a modeling framework to demonstrate potential prognostic factors of survival and evaluate the efficacy of different therapies., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

This study used a calibrated mathematical model to evaluate age-specific tuberculosis (TB) vaccination strategies, for drug-resistant (DR)-TB management in China. Prioritizing elderly vaccination significantly reduced multidrug-resistant or rifampicin-resistant TB incidence and mortality, while avoiding the need for second-line treatment, offering a promising approach to mitigate DR-TB burden by 2050., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients., Methods: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology., Results: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS., Conclusions: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

Background and Aims: Early detection of hepatocellular carcinoma (HCC) is crucial for improving survival in patients with chronic hepatitis. The GALAD algorithm combines gender (biological sex), age, α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC detection. Similarly, the GAAD algorithm incorporates gender (biological sex), age, AFP, and PIVKA-II. This study aimed to assess the clinical utility of AFP-L3 in the GALAD algorithm and its potential synergies with ultrasound. We compared the clinical performance of GALAD with GAAD; AFP; AFP-L3; and PIVKA-II, with or without ultrasound, in Taiwanese adults., Methods: A total of 439 serum samples were analyzed using a Cobas ® e 601 analyzer (healthy controls, n = 200; chronic liver disease controls, n = 177; HCC cases, n = 62). Performance was assessed through receiver operating characteristic curve analyses to calculate the area under the curve., Results: The area under the curve for differentiating early-stage HCC from patients with chronic liver disease was optimal for PIVKA-II (84.9%), GAAD (79.8%), and GALAD (79.4%), with slightly improved performance for detecting all-stage HCC. Clinical performance was unaffected by disease stage or etiology. Sensitivity for early-stage HCC was highest for GAAD (57.6%) and GALAD (57.6%). Sensitivity for each strategy was further enhanced when combined with ultrasound, regardless of disease stage or etiology ( P < 0.01)., Conclusions: These findings indicate that the role of AFP-L3 in the GALAD algorithm is minimal, supporting the use of GAAD for HCC detection. A combination of GAAD, GALAD, or PIVKA-II with ultrasound may improve diagnostic efficiency compared with recommended strategies., Competing Interests: WLC: Member of advisory boards for Gilead, AbbVie, Vaccitech, PharmaEssentia; speaker for Gilead, AbbVie, BMS, Roche, and has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2022. CFH: Speaker for AbbVie, BMS, Gilead, Merck, and Roche, JFH: Consultant for Roche, Gilead, Sysmex, and Aligos; speaker for AbbVie, Gilead, and Sysmex; and has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2022. MLYu: Research grants from AbbVie, Gilead, Merck, and Roche Diagnostics; consultant for AbbVie, BMS, Gilead, Roche, and Roche Diagnostics; and speaker for AbbVie, BMS, Eisai, Gilead, Roche, and Roche Diagnostics; and has been an Associate Editor of Journal of Clinical and Translational Hepatology since 2023. AS is an employee of Roche Diagnostics International AG. KK is an employee of Roche Diagnostics GmbH. MLYeh has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2022. The other authors have no conflict of interests related to this publication., (© 2024 Authors.)

Oral diseases represent a prevalent global health burden, profoundly affecting patients' quality of life. Given the involvement of oral mucosa and muscles in diverse physiological functions, coupled with clinical aesthetics considerations, repairing oral and maxillofacial soft tissue defects poses a formidable challenge. Wet-adhesive materials are regarded as promising oral repair materials due to their unique advantages in easily overcoming physical and biological barriers in the oral cavity. This review first introduces the intricate wet-state environment prevalent in the oral cavity, meticulously explaining the fundamental physical and chemical adhesion mechanisms that underpin adhesive materials. It then comprehensively summarizes the diverse types of adhesives utilized in stomatology, encompassing polysaccharide, protein, and synthetic polymer adhesive materials. The review further evaluates the latest research advancements in utilizing these materials to treat various oral and maxillofacial soft tissue diseases, including oral mucosal diseases, periodontitis, peri-implantitis, oral and maxillofacial skin defects, and maxillofacial tumors. Finally, it also highlights the promising future prospects and pivotal challenges related to stomatology application of multifunctional adhesive materials., (© 2024 Wiley‐VCH GmbH.)

Background: Non-coding RNAs have received increasing attention in human tumors, with RNA interaction networks playing important roles in breast cancer. This study aims to explore novel circular RNAs and their mechanisms of biological function in breast cancer., Methods: Six HER2-positive breast cancer tissues and paired normal tissues were obtained for the whole transcriptome RNA sequencing. Differentially expressed (DE) circRNAs, miRNAs and mRNAs were identified and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DERNAs were performed. DECircRNAs- DEmiRNAs- DEmRNAs networks were constructed and further verified by bioinformatics database analyses, luciferase assays and RIP assays. The expression level of circDOCK1 in breast cancer specimens was measured using qRT-PCR. Functional rescue experiments were conducted to explore the role of circDOCK1/miR-138-5p/GRB7 axis in breast cancer cells. The correlation of circDOCK1 expression and clinicopathologic features of 102 HER2 positive breast cancer patients was analyzed., Results: A total of 6960 DEmRNAs, 133 DE miRNAs and 1691 DE circRNAs were identified from HER2-positive breast cancer tissues and paracancerous tissues. Enrichment Analysis showed that the differential mRNAs were associated with cell division in biological processes and cell cycle and signaling pathways. GO and KEGG analysis demonstrated that DE circRNAs were mainly enriched in double-strand break repair, positive regulation of transcription by RNA polymerase II, nucleoplasma, nucleus, chromatin binding and protein binding. Forty networks of competing endogenous RNAs (ceRNAs) were constructed and circDOCK1/miR-138-5p/GRB7 axis was verified. Functional experiments revealed that the axis promotes migration and invasion of breast cancer cells. CircDOCK1 expression was elevated in breast cancer patients and correlated with adverse clinicopathologic parameters. Patients with high circDOCK1 level had poor outcomes., Conclusion: A novel circDOCK1/miR-138-5p/GRB7 axis promotes HER2 positive breast cancer metastasis and progression, providing a potential therapeutic target in the treatment of breast cancer., Competing Interests: The authors declare that they have no competing interests., (© 2024 Zhang et al.)

Background and Aims: To investigate the association between air pollution and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues., Methods: We enrolled 1298 CHB patients treated with nucleotide/nucleoside analogues and analysed the incidence and risk factors for HCC. Daily estimates of air pollutants were estimated since the previous year from the enrolment date., Results: The annual incidence of HCC was 2.1/100 person-years after a follow-up period of over 4840.5 person-years. Factors with the strongest association with HCC development were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 3.00/1.55-5.81; p = 0.001), male sex (2.98/1.51-5.90; p = 0.02), body mass index (1.11/1.04-1.18; p = 0.002) and age (1.06/1.04-1.09; p < 0.001). Among patients with cirrhosis, the factors associated with HCC development were male sex (HR/95% CI: 2.10/1.00-4.25; p = 0.04) and NO 2 (per one-unit increment, parts per billion; 1.07/1.01-1.13; p = 0.01). Moreover, patients with the highest quartile of annual NO 2 exposure had more than a three-fold risk of HCC than those with the lowest quartile of annual exposure (HR/95% CI: 3.26/1.34-7.93; p = 0.01). Among patients without cirrhosis, the strongest factors associated with HCC development were male sex (HR/95% CI: 5.86/1.79-19.23; p = 0.004), age (1.12/1.07-1.17; p < 0.001) and platelet count (0.99/0.98-1.00; p = 0.04)., Conclusions: Air pollution influences HCC development in CHB patients who receive nucleotide/nucleoside analogue therapy. Long-term NO 2 exposure might accelerate HCC development in CHB patients with cirrhosis receiving nucleotide/nucleoside analogue treatment., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: China faces the highest burden of latent multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB). We aim to evaluate the health and economic impacts of Vaccae (a novel TB vaccine) and enhanced drug-resistant TB (DR-TB) management strategies., Methods: Using a compartmental model calibrated with national TB data, we evaluated nine interventions from 2025-2050: enhanced DR-TB management (S1); Vaccae vaccination for those with Mycobacterium tuberculosis infection targeting specific age groups (S2: adolescents, S3: adolescents and young adults, S4: working-age adults, S5: elderly); and combined strategies (S6: S2+S1, S7: S3+S1, S8: S4+S1, S9: S5+S1). Vaccae's efficacy was set at 0.547 for the first five years, and then waning annually by 0.036. Costs were US$28/dose for Vaccae, US$87/test for Xpert MTB/RIF (diagnostic), and US$13,818/course for BPaLM (novel short regimen). Using a cost-effectiveness frontier, we identified the optimal strategy providing the greatest health benefit while remaining cost-effective., Results: Strategy S1 is projected to reduce MDR/RR-TB incidence and mortality by 21% (8%-46%) and 54% (38%-67%) by 2050. The combined strategy S9 (S5+S1) is more effective, reducing the incidence by 44% (35%-61%) and mortality by 68% (52%-78%), with an ICER of US$7,222 (4,460-10,779) per DALY averted compared with S1, highlighting its cost-effectiveness. Additionally, S9 could prevent 24.2 (13.5-32.9) million patient-months of second-line treatment from 2025 to 2050., Conclusions: Prioritizing Vaccae vaccination for the elderly and enhancing DR-TB management offers a promising and cost-effective opportunity to DR-TB control in China. The findings may inform vaccination policies in other low- and middle-income countries with high MDR/RR-TB burden., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Trastuzumab-targeted therapy is currently the standard of care for advanced human epidermal growth factor receptor 2 (HER2)-positive gastric cancer. However, the emergence of resistance to trastuzumab poses significant challenges., Aim: To identify the key genes associated with trastuzumab resistance. These results provide a basis for the development of interventions to address drug resistance and improve patient outcomes., Methods: High-throughput sequencing and bioinformatics were used to identify the differentially expressed pivotal gene BIRC3 and delineate its potential function and pathway regulation. Tumor samples were collected from patients with HER2-positive gastric cancer to evaluate the correlation between BIRC3 expression and trastuzumab resistance. We established gastric cancer cell lines with both highly expressed and suppressed levels of BIRC3 , followed by comprehensive in vitro and in vivo experiments to confirm the involvement of BIRC3 in trastuzumab resistance and to elucidate its underlying mechanisms., Results: In patients with HER2-positive gastric cancer, there is a significant correlation between elevated BIRC3 expression in tumor tissues and higher T stage, tumor node metastasis stage, as well as poor overall survival and progression-free survival. BIRC3 is highly expressed in trastuzumab-resistant gastric cancer cell lines, where it inhibits tumor cell apoptosis and enhances trastuzumab resistance by promoting the phosphorylation and activation of the phosphoinositide 3-kinase-Akt (PI3K-AKT) pathway in HER2-positive gastric cancer cells, both in vivo and in vitro ., Conclusion: This study revealed a robust association between high BIRC3 expression and an unfavorable prognosis in patients with HER2-positive gastric cancer. Thus, the high expression of BIRC3 stimulated PI3K-AKT phosphorylation and activation, stimulating the proliferation of HER2-positive tumor cells and suppressing apoptosis, ultimately leading to trastuzumab resistance., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Treatment of articular cartilage injury remains a challenging clinical problem in orthopedics. Chitosan-derived biomaterial could be a potential adjuvant treatment to improve cartilage repair. In the current study, we examined the effects of two potential chitosan-derived materials on cartilage regeneration of osteochondral defects in rabbits., Methods: An osteochondral defect was created over the rabbit knee and treated using three approaches: group A received no material (n = 24), group B received chitosan membranes with glucose absorption (CGA; n = 25), and group C received chitosan-glucose derivative membranes obtained via the Maillard reaction (CGMR; n = 25). Cartilage repair over the osteochondral defect was analyzed 12 weeks post-surgery via histological analysis, immunostaining, and reverse transcription-qualitative polymerase chain reaction (RT-qPCR) for type-I and type-II collagen mRNA., Results: According to histological analysis, CGMR-treated defects showed significantly improved modified O'Driscoll scoring when compared with no material- and CGA-treated defects (20.9 ± 4.3 vs. 13.00 ± 2.5 and 17.7 ± 4.6, p < 0.001). Moreover, group C exhibited higher intensity of type-II collagen immunohistochemical staining over the regenerated cartilage than groups A and B, along with increased expression of type-II collagen mRNA by RT-qPCR., Conclusions: CGMR might improve cartilage regeneration in osteochondral defects., (© 2024. The Author(s).)

Background: Emerging adult (EA) cannabis use is associated with increased risk for health consequences. Just-in-time adaptive interventions (JITAIs) provide potential for preventing the escalation and consequences of cannabis use. Powered by mobile devices, JITAIs use decision rules that take the person's state and context as input, and output a recommended intervention (e.g., alternative activities, coping strategies). The mHealth literature on JITAIs is nascent, with additional research needed to identify what intervention content to deliver when and to whom., Methods: Herein we describe the protocol for a pilot study testing the feasibility and acceptability of a micro-randomized trial for optimizing MiWaves mobile intervention app for EAs (ages 18-25; target N = 120) with regular cannabis use (≥3 times per week). Micro-randomizations will be determined by a reinforcement learning algorithm that continually learns and improves the decision rules as participants experience the intervention. MiWaves will prompt participants to complete an in-app twice-daily survey over 30 days and participants will be micro-randomized twice daily to either: no message or a message [1 of 6 types varying in length (short, long) and interaction type (acknowledge message, acknowledge message + click additional resources, acknowledge message + fill in the blank/select an option)]. Participants recruited via social media will download the MiWaves app, and complete screening, baseline, weekly, post-intervention, and 2-month follow-up assessments. Primary outcomes include feasibility and acceptability, with additional exploratory behavioral outcomes., Conclusion: This study represents a critical first step in developing an effective mHealth intervention for reducing cannabis use and associated harms in EAs., Competing Interests: Declaration of competing interest Susan Murphy holds concurrent appointments as a Professor of Statistics and Computer Science at Harvard University and as an Amazon Scholar. This paper describes work performed at Harvard University and is not associated with Amazon., (Copyright © 2024. Published by Elsevier Inc.)

Background and Aims: We aimed to explore the risk factors associated with virological and clinical relapse, as well as their impact on overall mortality, in hepatitis B virus (HBV)-infected patients receiving nucleos(t)ide analogues (NUCs) therapy prior to chemotherapy initiation., Methods: From 2010 to 2020, we conducted a prospective cohort study involving patients with HBV infection undergoing cytotoxic chemotherapy. We utilized the Kaplan-Meier method and Cox proportional hazard regression models to assess risk factors., Results: We observed that TDF or TAF (HR: 2.16, 95% CI 1.06-4.41; p = .034), anthracycline (HR: 1.73, 95% CI 1.10-2.73; p = .018), baseline HBV DNA (HR: 1.55, 95% CI 1.33-1.81; p < .001) and end-of-treatment HBsAg titre >100 IU/mL (HR: 7.81, 95% CI 1.94-31.51; p = .004) were associated with increased risk of virological relapse. Additionally, TDF or TAF (HR: 4.91, 95% CI 1.45-16.64; p = .011), baseline HBV DNA (HR: 1.48, 95% CI 1.10-1.99; p = .009) and end-of-treatment HBsAg titre >100 IU/mL (HR: 6.09, 95% CI .95-38.87; p = .056) were associated with increased risk of clinical relapse. Furthermore, we found that virological relapse (HR: 3.32, 95% CI 1.33-8.32; p = .010) and clinical relapse (HR: 3.59, 95% CI 1.47-8.80; p = .005) significantly correlated with all-cause mortality in HBV patients receiving cytotoxic chemotherapy with prophylactic NUCs therapy., Conclusions: The risk of virological and clinical relapse was linked to baseline HBV DNA, end-of-treatment HBsAg levels and TDF or TAF for prophylaxis; additionally, experiencing relapse heightens the risk of all-cause mortality. Further research is warranted to explore potential strategies for preventing virological and clinical relapse in high-risk patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Chromothripsis, a type of complex chromosomal rearrangement originally known as chromoanagenesis, has been a subject of extensive investigation due to its potential role in various diseases, particularly cancer. Chromothripsis involves the rapid acquisition of tens to hundreds of structural rearrangements within a short period, leading to complex alterations in one or a few chromosomes. This phenomenon is triggered by chromosome mis-segregation during mitosis. Errors in accurate chromosome segregation lead to formation of aberrant structural entities such as micronuclei or chromatin bridges. The association between chromothripsis and cancer has attracted significant interest, with potential implications for tumorigenesis and disease prognosis. This review aims to explore the intricate mechanisms and consequences of chromothripsis, with a specific focus on its association with mitotic perturbations. Herein, we discuss a comprehensive analysis of crucial molecular entities and pathways, exploring the intricate roles of the CIP2A-TOPBP1 complex, micronuclei formation, chromatin bridge processing, DNA damage repair, and mitotic checkpoints. Moreover, the review will highlight recent advancements in identifying potential therapeutic targets and the underlying molecular mechanisms associated with chromothripsis, paving the way for future therapeutic interventions in various diseases., (© The Author(s) (2024). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

Circular RNAs (circRNAs) are now recognized as key regulators in the epigenetic control of genetic expression, being involved in a wide range of cellular activities such as proliferation, differentiation, and apoptosis. Their unique closed-loop structure endows them with stability and resistance to exonuclease degradation, making them not only key regulatory molecules within the cell but also promising biomarkers for disease diagnosis and prognosis, particularly in hematological malignancies. This review comprehensively explores the role of circRNAs in the pathogenesis, progression, and therapeutic resistance of common hematological malignancies. Furthermore, the review delves into the prognostic significance of circRNAs, underscoring their potential in predicting disease outcomes and treatment response. Given their extensive involvement in cancer biology, circRNAs present a frontier for novel therapeutic strategies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Infections in patients with hematological malignancies (HM) are a significant cause of morbidity and mortality. Timely and effective empirical anti-infective treatment can reduce the infection-related mortality rate. Targeted next-generation sequencing (tNGS) offers a rapid diagnostic approach for identifying diverse pathogens in these patients. However, relevant research is still limited to adult patients with HM., Methods: We conducted a retrospective analysis of adult HM patients admitted to our hospital from March 2023 to September 2023, focusing on their clinical characteristics and the results of both tNGS and conventional microbiological tests (CMTs). We evaluated the performance of tNGS and CMTs in pathogenic diagnosis and described the distribution characteristics of pathogens in adult HM patients with infections., Results: The study included 209 samples collected from 137 patients. Results showed that the overall pathogen detection rate differed significantly between tNGS and CMTs (60.3% vs. 24.4%, p  < 0.001). The sensitivity (69.7% vs. 35.9%), negative predictive value (NPV) (48.2% vs. 42.4%), and accuracy (66.5% vs. 56.5%) of pathogen detection were notably superior with tNGS compared to CMTs. Among the 142 samples with clinically diagnosed infections, tNGS combined with CMTs identified a definite or probable microbial etiology in 114 samples (80.3%). Of the 36 samples with concordant positive results from both tNGS and CMTs, 72.2% (26/36) exhibited full or partial agreement. Our study further showed the highest detection rate for viral infections (57.0%), predominantly for Epstein-Barr virus (DNA-V, 18.3%). Followed by bacterial infections (46.5%), the detection rate of Gram-negative bacteria (G + , 35.9%) was higher than that of Gram-positive bacteria (G - , 21.8%) in this study. Klebsiella pneumoniae (G - , 12.7%) had the highest detection rate among these emerging bacteria, followed by Pseudomonas aeruginosa (G - , 10.6%) and Enterococcus faecium (G + , 7.7%). Bacterial-viral coinfections were the most common type of mixed infection (35.5%)., Conclusion: In conclusion, tNGS outperforms CMTs in both sensitivity and pathogen spectrum. Therefore, it can serve as an adjunct to CMTs to facilitate the precise adjustment of anti-infective regimens for adult HM patients. Our findings establish a basis for formulating empirical anti-infective therapy strategies tailored to the pathogen distribution in this patient population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Cui, Wang, Nan, Yang, Bai and Shi.)

Introduction: Tuberculosis (TB) is a major global health issue, particularly, in India and South Africa. We aim to evaluate the potential of the new TB vaccine, Vaccae, to enhance TB control by integrating with active case finding (ACF) strategies in these regions., Methods: Using age-structured dynamic models, we projected the epidemiological and economic outcomes of combining Vaccae vaccination with ACF over 27 years. In India, four age-targeted strategies were analysed: (1) adolescent (15 years), (2) adolescent and young adult (AYA, 15-34 years), (3) adult (18-55 years) and (4) elderly (60+ years). In South Africa, strategies were based on HIV status: (1) HIV-targeted, (2) non-HIV and (3) general population. The vaccine efficacy of Vaccae was set at 54.7%, priced at US$120 per course. Outcomes measured included reductions in TB incidence and mortality, prioritised based on budget, incremental cost-effectiveness ratios (ICER) and benefit-cost ratios (BCR)., Results: In India, the adult strategy could prevent 8.70 (95% UI: 6.86-11.13) million TB cases and 0.61 (0.39-0.91) million deaths, reducing incidence and mortality by 20.1% (18.7%-23.5%) and 19.0% (17.5%-22.5%), respectively. In South Africa, the general population strategy could avert 0.67 (0.45-0.99) million TB cases and 0.21 (0.15-0.28) million deaths, reducing incidence by 28.1% (26.1%-30.3%) and mortality by 27.0% (23.5%-30.0%). The vaccination budgets for the AYA strategy in India and the HIV-targeted strategy in South Africa were US$14.0 (10.14-23.29) billion and US$0.09 (0.06-0.15) billion, respectively. The ICERs were US$1082 (927-1426) and US$70 (53-123) per disability-adjusted life year averted, and the BCRs were 2.0 (1.6-2.4) and 176 (83.4-255.3), respectively. Thus, the AYA strategy in India and the HIV-targeted strategy in South Africa were the most favourable., Conclusion: Integrating Vaccae vaccination with ACF could significantly enhance TB control in high-burden countries. Policymakers should consider these strategies, with further research needed to confirm the findings., Competing Interests: GQ is an editorial board member of BMJ Public Health. The remaining authors have no conflicts of interest to declare., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. Published by BMJ.)

Partitioning of repressive from actively transcribed chromatin in mammalian cells fosters cell-type-specific gene expression patterns. While this partitioning is reconstructed during differentiation, the chromatin occupancy of the key insulator, CCCTC-binding factor (CTCF), is unchanged at the developmentally important Hox clusters. Thus, dynamic changes in chromatin boundaries must entail other activities. Given its requirement for chromatin loop formation, we examined cohesin-based chromatin occupancy without known insulators, CTCF and Myc-associated zinc-finger protein (MAZ), and identified a family of zinc-finger proteins (ZNFs), some of which exhibit tissue-specific expression. Two such ZNFs foster chromatin boundaries at the Hox clusters that are distinct from each other and from MAZ. PATZ1 was critical to the thoracolumbar boundary in differentiating motor neurons and mouse skeleton, while ZNF263 contributed to cervicothoracic boundaries. We propose that these insulating activities act with cohesin, alone or combinatorially, with or without CTCF, to implement precise positional identity and cell fate during development., Competing Interests: Declaration of interests D.R. was a co-founder of Constellation Pharmaceuticals and Fulcrum Therapeutics. Currently, D.R. has no affiliation with either company., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The main bioactive components of agarwood, derived from Aquilaria sinensis, include sesquiterpenes, 2-(2-phenethyl) chromone derivatives, aromatic compounds, and fatty acids, which typically exert anti-inflammatory, antioxidant, immune-modulating, hypoglycemic, and antitumor pharmacological effects in the form of essential oils. Agarwood tree leaves, rich in flavonoids, 2-(2-phenethyl) chromone compounds, and flavonoid compounds, also exhibit significant anti-inflammatory, antioxidant, and immune-modulating effects. These properties are particularly relevant to the treatment of periodontitis, given that inflammatory responses, oxidative stress, and immune dysregulation are key pathological mechanisms of the disease, highlighting the substantial potential of agarwood and agarwood tree leaves in this therapeutic area. However, the low solubility and poor bioavailability of essential oils present challenges that necessitate the development of improved active formulations. In this review, we will introduce the bioactive components, extraction methods, pharmacological actions, and clinical applications of agarwood and agarwood tree leaves, analyzing its prospects for the treatment of periodontitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xie, Dong, Lu, Yan, Zhao, Ding, Lv and Zheng.)

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) may potentially delay or cause non-union of fractures by inhibiting prostaglandin synthesis. However, studies have shown conflicting results. This systematic review and meta-analysis aim to synthesize current evidence on the potential influence of NSAIDs on bone healing., Methods: We conducted a comprehensive search of PubMed, Embase, and Cochrane CENTRAL databases for studies published up to 25 July 2023. Specific keywords included "NSAID," "nonsteroidal anti-inflammatory drug," "cyclooxygenase-2 inhibitor," "bone healing," "non-union," "pseudoarthrosis," "delayed union," and "atrophic bone." Eligible studies included prospective, retrospective, and case-controlled studies assessing the correlation between NSAID use and bone healing outcomes. The leave-one-out approach was used to test the robustness of the meta-analysis results., Results: A total of 20 studies with 523,240 patients were included in the analysis. The mean patient age ranged from 6.7 to 77.0 years, with follow-up durations from 3 to 67 months. The meta-analysis revealed no significant difference in non-union or delayed union between NSAID users and non-users [pooled adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 0.99-1.23]. Initial analysis identified a significant association between NSAID usage and an increased risk of reoperation, but this association became insignificant upon sensitivity analysis (crude OR = 1.42; 95% CI: 0.88-2.28)., Discussion: NSAIDs may have a minimal impact on non-union or delayed union risks. However, caution is advised due to the limited number of studies and the absence of a specific focus on NSAID types and dosages. Further research is necessary to better understand the implications of NSAID use on bone healing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chuang, Yang, Tsai and Huang.)

Importance: Organophosphate flame retardants (OPFRs) are an important group of pollutants associated with endocrine disorders, cancer, and nephrotoxicity. However, temporal trends in OPFR metabolite concentrations remain understudied., Objectives: To examine changes in urinary concentrations of OPFR metabolites among US children, youths, and adults from 2011 to 2020, and to evaluate whether sociodemographic factors were associated with variations in temporal trends., Design, Setting, and Participants: This population-based cross-sectional study used data from 4 US National Health and Nutrition Examination Survey (NHANES) cycles (2011-2012, 2013-2014, 2015-2016, and 2017-2020 [to March 2020 before the COVID-19 pandemic]). The study included children and youths (aged 6-19 years) and adults (aged ≥20 years) with valid urinary concentrations of the following OPFR metabolites: bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), diphenyl phosphate (DPhP), and dibutyl phosphate (DBuP). Data analysis was performed between February and May 2024., Exposures: Calendar year and key sociodemographic subgroups (age, race and ethnicity, sex, educational attainment, and poverty-to-income ratio)., Main Outcomes and Measures: The main outcome was urinary concentrations of OPFR metabolites among children, youths, and adults. Survey-weighted linear regression models were applied to estimate trends., Results: The study population of 10 549 NHANES participants included 3154 children and youths (mean [SE] age, 12.5 [0.1] years; 51.2% were male) and 7395 adults (mean [SE] age, 47.8 [0.4] years; 52.0% were women). Among children and youths, mean (95% CI) BCEtP concentrations decreased from 0.68 (0.60-0.77) μg/L in 2011-2012 to 0.41 (0.37-0.45) μg/L in 2017-2020 (P for trend < .001). Among adults, mean (95% CI) BCEtP concentrations decreased from 0.43 (0.37-0.50) μg/L in 2011-2012 to 0.29 (0.27-0.33) μg/L in 2017-2020 (P for trend < .001), and mean BCPP concentrations decreased from 0.15 (0.14-0.17) μg/L to 0.13 (0.12-0.14) μg/L (P for trend = .002). Parent level of educational attainment was associated with concentrations of BCPP and BCEtP among children and youths; however, no significant differences among adults were observed., Conclusions and Relevance: This study identified variations in temporal trends in urinary concentrations of OPFR metabolites among the US population from 2011 to 2020. In addition, substantial disparities in exposure levels persisted among children with different levels of parent educational attainment. These findings suggest that policy makers should consider socioeconomic factors to further reduce OPFR exposure and promote equity, ensuring a safe living environment for all individuals.

The external electric field has emerged as a powerful tool for building molecular switches with excellent properties. In this work, we investigate the impact of an external electric field on the transition between lithium salt and electride-like molecule conformations in Li@corannulene. Remarkably, the distance between the Li atom and the corannulene bottom displays a sharp increase under the influence of an external electric field strength of F - z = 110 × 10 -4 a.u. As the external electric field strength increases, the Li atom brings about different directions of charge transfer (CT). The natural population analysis (NPA) charge and the molecular electrostatic potential (ESP) results show that the intermolecular CT occurs from the Li atom to the corannulene with the F - z ranging from 0 to 100 × 10 -4 a.u. Interestingly, when the external electric field reaches F - z = 110 × 10 -4 a.u., the CT is oriented from the corannulene to the Li atom. Moreover, electron localization function (ELF) basins are presented under an F - z of 110 × 10 -4 a.u., which indicates that Li@corannulene exhibits electride-like (e - ⋯[Li@corannulene] + ) molecules and lithiation salt (Li + [corannulene] - ) under an F - z of 0 to 100 × 10 -4 a.u. Significantly, the differences in charge transfer also contribute to a significant improvement in hyperpolarizabilities ( β tot ) during the conformation transition from lithiation salt (Li + [corannulene] - ) to electride-like (e - ⋯[Li@corannulene] + ) molecules. This study explores the potential of Li@corannulene as a promising second-order NLO material, and the external electric field provides an efficient strategy for designing and developing NLO switching devices.

Background and Objectives : Our study compared the visual and anatomical outcomes of polypoidal choroidal vasculopathy (PCV) patients receiving intravitreal aflibercept (IVA) with or without photodynamic therapy (PDT) over 12 months. Materials and Methods : This retrospective study was performed for 60 eyes from 60 patients with treatment-naïve PCV. Thirty eyes were treated using IVA monotherapy (IVA group), and thirty eyes were treated using a combination of IVA with PDT (IVA/PDT group). The baseline characteristics, treatment outcomes, and retreatment rates were compared between the two groups over a one-year follow-up period. Results : The best-corrected visual acuity (BCVA) was found to have improved significantly in the IVA/PDT group at every 3-month visit. However, no significant BCVA improvement was observed in the IVA group. A significantly lower retreatment rate and higher dry macula rate were found in the IVA/PDT group than that in the IVA group. In the entire population of the study, a better baseline vision and younger age were associated with better final visual outcomes. Retreatment was associated with poor baseline BCVA and IVA monotherapy. Conclusions : The combination of IVA and PDT may offer superior visual improvement and a higher dry macula rate compared to IVA monotherapy in the treatment of PCV patients while requiring fewer retreatments over 12 months.

Blastocyst vitrification has significantly improved embryo transfer methods, leading to higher implantation success rates and better pregnancy outcomes in subsequent frozen embryo transfer cycles. This study aimed to simulate the transcriptional changes caused by vitrifying human blastocysts using mouse blastocysts as a model and to further investigate these changes' effects. Utilizing a human vitrification protocol, we implanted both vitrified and fresh embryos into mice. We observed the implantation success rates and performed transcriptomic analysis on the blastocysts. To validate the results from messenger RNA sequencing, we conducted reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) to measure the expression levels of specific genes. Based on mRNA profiling, we predicted the microRNAs responsible for the regulation and used qPCR basic microRNA assays for validation. Our observations revealed a higher implantation success rate for vitrified embryos than fresh embryos. Transcriptomic analysis showed that vitrified-warmed blastocysts exhibited differentially expressed genes (DEGs) primarily associated with thermogenesis, chemical carcinogenesis-reactive oxygen species, oxidative phosphorylation, immune response, and MAPK-related signaling pathways. RT-qPCR confirmed increased expression of genes such as Cdk6 and Nfat2 , and decreased expression of genes such as Dkk3 and Mapk10 . Additionally, gene-microRNA interaction predictions and microRNA expression analysis identified twelve microRNAs with expression patterns consistent with the predicted results, suggesting potential roles in uterine epithelial cell adhesion, trophectoderm development, invasive capacity, and immune responses. Our findings suggest that vitrification induces transcriptomic changes in mouse blastocysts, and even small changes in gene expression can enhance implantation success. These results highlight the importance of understanding the molecular mechanisms underlying vitrification to optimize embryo transfer techniques and improve pregnancy outcomes.

Introduction: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated., Objectives: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M)., Material and Methods: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations., Results: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations., Conclusion: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof., (© 2024 John Wiley & Sons Ltd.)

Background: Pancreatic cancer (PanCa), ranked as the 4th leading cause of cancer-related death worldwide, exhibits an dismal 5-year survival rate of less than 5 %. Chronic pancreatitis (CP) is a known major risk factor for PanCa. Brusatol (BRT) possesses a wide range of biological functions, including the inhibition of PanCa proliferation. However, its efficacy in halting the progression from CP to pancreatic carcinogenesis remains unexplored., Methods: We assess the effects of BRT against pancreatic carcinogenesis from CP using an experimentally induced CP model with cerulein, and further evaluate the therapeutic efficacy of BRT on PanCa by employing Kras tm4Tyj Trp53 tm1Brn Tg (Pdx1-cre/Esr1*) #Dam/J (KPC) mouse model., Results: Our finding demonstrated that BRT mitigated the severity of cerulein-induced pancreatitis, reduced pancreatic fibrosis and decreased the expression of α-smooth muscle actin (α-SMA), which is a biomarker for pancreatic fibrosis. In addition, BRT exerted effects against cerulein-induced pancreatitis via inactivation of NLRP3 inflammasome. Moreover, BRT significantly inhibited tumor growth and impeded cancer progression., Conclusions: The observed effect of BRT on impeding pancreatic carcinogenesis through targeting NLRP3 inflammasome suggests its good potential as a potential agent for treatment of PanCa., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The escalating prevalence of cannabis use, and associated cannabis-use disorder (CUD), poses a significant public health challenge globally. With a notably wide treatment gap, especially among emerging adults (EAs; ages 18-25), addressing cannabis use and CUD remains a pivotal objective within the 2030 United Nations Agenda for Sustainable Development Goals (SDG). In this work, we develop an online reinforcement learning (RL) algorithm called reBandit which will be utilized in a mobile health study to deliver personalized mobile health interventions aimed at reducing cannabis use among EAs. reBandit utilizes random effects and informative Bayesian priors to learn quickly and efficiently in noisy mobile health environments. Moreover, reBandit employs Empirical Bayes and optimization techniques to autonomously update its hyper-parameters online. To evaluate the performance of our algorithm, we construct a simulation testbed using data from a prior study, and compare against commonly used algorithms in mobile health studies. We show that reBandit performs equally well or better than all the baseline algorithms, and the performance gap widens as population heterogeneity increases in the simulation environment, proving its adeptness to adapt to diverse population of study participants.

Background: For in vitro fertilization (IVF), mitochondrial DNA (mtDNA) levels in the trophectodermal (TE) cells of biopsied blastocysts have been suggested to be associated with the cells' developmental potential. However, scholars have reached differing opinions regarding the use of mtDNA levels as a reliable biomarker for predicting IVF outcomes. Therefore, this study aims to assess the association of mitochondrial copy number measured by mitoscore associated with embryonic developmental characteristics and ploidy., Methods: This retrospective study analyzed the developmental characteristics of embryos and mtDNA levels in biopsied trophectodermal cells. The analysis was carried out using time-lapse monitoring and next-generation sequencing from September 2021 to September 2022. Five hundred and fifteen blastocysts were biopsied from 88 patients undergoing IVF who met the inclusion criteria. Embryonic morphokinetics and morphology were evaluated at 118 h after insemination using all recorded images. Blastocysts with appropriate morphology on day 5 or 6 underwent TE biopsy and preimplantation genetic testing for aneuploidy (PGT-A). Statistical analysis involved generalized estimating equations, Pearson's chi-squared test, Fisher's exact test, and Kruskal-Wallis test, with a significance level set at P < 0.05., Results: To examine differences in embryonic characteristics between blastocysts with low versus high mitoscores, the blastocysts were divided into quartiles based on their mitoscore. Regarding morphokinetic characteristics, no significant differences in most developmental kinetics and observed cleavage dysmorphisms were discovered. However, blastocysts in mitoscore group 1 had a longer time for reaching 3-cell stage after tPNf (t3; median: 14.4 h) than did those in mitoscore group 2 (median: 13.8 h) and a longer second cell cycle (CC2; median: 11.7 h) than did blastocysts in mitoscore groups 2 (median: 11.3 h) and 4 (median: 11.4 h; P < 0.05). Moreover, blastocysts in mitoscore group 4 had a lower euploid rate (22.6%) and a higher aneuploid rate (59.1%) than did those in the other mitoscore groups (39.6-49.3% and 30.3-43.2%; P < 0.05). The rate of whole-chromosomal alterations in mitoscore group 4 (63.4%) was higher than that in mitoscore groups 1 (47.3%) and 2 (40.1%; P < 0.05). A multivariate logistic regression model was used to analyze associations between the mitoscore and euploidy of elective blastocysts. After accounting for factors that could potentially affect the outcome, the mitoscore still exhibited a negative association with the likelihood of euploidy (adjusted OR = 0.581, 95% CI: 0.396-0.854; P = 0.006)., Conclusions: Blastocysts with varying levels of mitochondrial DNA, identified through biopsies, displayed similar characteristics in their early preimplantation development as observed through time-lapse imaging. However, the mitochondrial DNA level determined by the mitoscore can be used as a standalone predictor of euploidy., (© 2024. The Author(s).)

In eukaryotes, microtubule polymers are essential for cellular plasticity and fate decisions. End-binding (EB) proteins serve as scaffolds for orchestrating microtubule polymer dynamics and are essential for cellular dynamics and chromosome segregation in mitosis. Here, we show that EB1 forms molecular condensates with TIP150 and MCAK through liquid-liquid phase separation to compartmentalize the kinetochore-microtubule plus-end machinery, ensuring accurate kinetochore-microtubule interactions during chromosome segregation in mitosis. Perturbation of EB1-TIP150 polymer formation by a competing peptide prevents phase separation of the EB1-mediated complex and chromosome alignment at the metaphase equator in both cultured cells and Drosophila embryos. Lys220 of EB1 is dynamically acetylated by p300/CBP-associated factor in early mitosis, and persistent acetylation at Lys220 attenuates phase separation of the EB1-mediated complex, dissolves droplets in vitro, and harnesses accurate chromosome segregation. Our data suggest a novel framework for understanding the organization and regulation of eukaryotic spindle for accurate chromosome segregation in mitosis., (© The Author(s) (2024). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

Background and Aim: Endoscopic resection has been successfully used for the removal of digestive submucosal tumors (SMTs). However, the cardia has been considered a challenging location for endoscopic resection due to its narrow lumen and sharp angle. The objective of this study was to establish a clinical scoring model to grade the technical difficulty of endoscopic resection for cardial SMTs., Methods: A total of 246 patients who suffered cardial SMTs and received endoscopic resection were included in this retrospective study. All of them were randomized into the training cohort (n = 123) or internal validation cohort (n = 123). Potential predictors were analyzed using univariate analysis. Then, covariates with P < 0.05 were selected for the multivariate logistic regression model. The β coefficients from the logistic regression model were used to create a scoring system for technical difficulty prediction by rounding the score to the nearest integer of the absolute β coefficient value., Results: The clinical score consisted of the following factors: male gender (2 points), extraluminal growth (3 points), and maximum diameter ≥3 cm (3 points). The scoring model demonstrated good discriminatory power, with an area under the receiver operating characteristic curve of 0.860 and a 95% confidence interval of 0.763-0.958. The model also showed a good goodness of fit in the Hosmer-Lemeshow test (P = 0.979). In the training cohort, the probability of encountering technical difficulty in the easy (score = 0), intermediate (score = 1-3), difficult (score = 4-6), and very difficult (score >6) categories was 0, 6.8%, 33.3%, and 100.0%, respectively; similarly, in the validation cohort, it was 0, 5.6%, 22.2%, and 50.0%, respectively., Conclusions: This scoring system could serve as a valuable tool for clinicians in predicting the technical difficulty of endoscopic resection for cardial SMTs., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Decellularised extracellular matrix (dECM) is a biomaterial derived from natural tissues that has attracted considerable attention from tissue engineering researchers due to its exceptional biocompatibility and malleability attributes. These advantageous properties often facilitate natural cell infiltration and tissue reconstruction for regenerative medicine. Due to their excellent fluidity, the injectable hydrogels can be administered in a liquid state and subsequently formed into a gel state in vivo, stabilising the target area and serving in a variety of ways, such as support, repair, and drug release functions. Thus, dECM-based injectable hydrogels have broad prospects for application in complex organ structures and various tissue injury models. This review focuses on exploring research advances in dECM-based injectable hydrogels, primarily focusing on the applications and prospects of dECM hydrogels in tissue engineering. Initially, the recent developments of the dECM-based injectable hydrogels are explained, summarising the different preparation methods with the evaluation of injectable hydrogel properties. Furthermore, some specific examples of the applicability of dECM-based injectable hydrogels are presented. Finally, we summarise the article with interesting prospects and challenges of dECM-based injectable hydrogels, providing insights into the development of these composites in tissue engineering and regenerative medicine., Competing Interests: Conflicts of interest statement: The authors declare no competing financial interest.

Background: The adhesive properties of vitiligo melanocytes have decreased under oxidative stress., cytoskeleton proteins can control cell adhesion. Paeoniflorin (PF) was proved to resist hydrogen peroxide (H 2 O 2 )-induced oxidative stress in melanocytes via nuclear factorE2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway., Objectives: This study was to investigate whether PF exerts anti-oxidative effect through influencing cytoskeleton markers or potential signaling pathway., Methods: Human Oxidative Stress Plus array was used to identify the differentially expressed genes between H 2 O 2  + PF group and H 2 O 2 only group, in PIG1 and PIG3V melanocyte cell lines respectively. Western blotting was used to verify the PCR array results and to test the protein expression levels of cytoskeleton markers including Ras homolog family member A (RhoA), Rho-associated kinase 1 (ROCK1) and antioxidative marker Nrf2. Small interfering RNA was used to knock down PDZ and LIM domain 1 (PDLIM1)., Results: PF increased the expressions of PDLIM1, RhoA and ROCK1 in H 2 O 2 -induced PIG1, in contrast, decreased the expressions of PDLIM1 and ROCK1 in H 2 O 2 -induced PIG3V. Knockdown of PDLIM1 increased the expressions of RhoA and Nrf2 in PF-pretreated H 2 O 2 -induced PIG1, and ROCK1 and Nrf2 in PF-pretreated H 2 O 2 -induced PIG3V., Conclusions: PF regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in H 2 O 2 -induced melanocytes. In PIG1, PF promotes PDLIM1 to inhibit RhoA/ROCK1 pathway or activates Nrf2/HO-1 pathway, separately. In PIG3V, PF directly downregulates ROCK1 in PDLIM1-independent manner or upregulates Nrf2 dependent of PDLIM1., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Augmented reality is increasingly used in health care, yet little is known about how AR is being used in physical therapy practice and what clinical outcomes could occur with technology use. In this scoping review, a broad literature review was conducted to gain an understanding of current knowledge of AR use and outcomes in physical therapy practice. A structured literature search of articles published between 2000 to September 2023 that examined the use of AR in a physical therapy context was conducted. Reference lists of articles for full review were searched for additional studies. Data from articles meeting inclusion criteria were extracted and synthesized across studies. 549 articles were identified; 40 articles met criteria for full review. Gait and balance of neurological and older adult populations were most frequently targeted, with more recent studies including orthopedic and other populations. Approximately half were pilot or observational studies and half are experimental. Many studies found within group improvements. Of studies reporting between group differences, AR interventions were more effective in improving function almost half of the time, with 20%, 27% and 28% showing efficacy in disability, balance, and gait outcomes. AR in physical therapy holds promise; however, efficacy outcomes are unclear., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Pneumoconiosis, a chronic disease stemming from prolonged inhalation of dust particles, stands as a significant global burden of occupational diseases. This study aims to investigate the survival outcomes of pneumoconiosis patients in Huangshi city, China, while also evaluating the disease burden on afflicted patients., Methods: Data for this study were sourced from the Huangshi Center for Disease Control and Prevention. Survival analyses of pneumoconiosis patients were conducted employing life tables and the Kaplan-Meier method. The Cox proportional hazards models were deployed to identify factors influencing pneumoconiosis patients' survival duration. Competing risks models were employed to confirm the validity of the model outcomes. Additionally, in the disease burden assessment, disability-adjusted life years (DALYs) were computed for various demographic groups and time frames., Results: A total of 5,641 pneumoconiosis cases, diagnosed in Huangshi City, Hubei Province between 1958 and 2021, were incorporated into the cohort analysis. The probability of mortality and the risk ratio increased with advancing age. Notably, the median survival time of stage III pneumoconiosis patients was significantly shorter compared with those in stages I and II. The Cox proportional hazards model and competing risks analyses underscored several significant factors influencing survival time, including dust exposure duration (HR = 1.197, 95% CI: 1.104-1.298), age at first diagnosis (HR = 3.149, 95% CI: 2.961-3.349), presence of silicosis (HR = 1.378, 95% CI: 1.254-1.515), and stage II-III pneumoconiosis (HR = 1.456, 95% CI: 1.148-1.848). Cumulatively, DALYs amounted to 7,974.35 person-years, with an average of 1.41 person-years. The period between 2000 and 2019 witnessed the highest disease burden., Conclusion: Our findings highlight the urgent need for improved prevention, earlier detection, and more effective management strategies for the occupational pneumoconiosis population. This study not only underscores the persistent issue of pneumoconiosis in industrial environments but also serves as a crucial call to action for policymakers and healthcare providers., (© 2024. The Author(s).)

Higher intensity exercise, despite causing more tissue damage, improved aging conditions. We previously observed decreased p16 INK4a mRNA in human skeletal muscle after high-intensity interval exercise (HIIE), with no change following equivalent work in moderate-intensity continuous exercise. This raises the question of whether the observed senolytic effect of exercise is mediated by inflammation, an immune response induced by muscle damage. In this study, inflammation was blocked using a multiple dose of ibuprofen (total dose: 1200 mg), a commonly consumed nonsteroidal anti-inflammatory drug (NSAID), in a placebo-controlled, counterbalanced crossover trial. Twelve men aged 20-26 consumed ibuprofen or placebo before and after HIIE at 120% maximum aerobic power. Multiple muscle biopsies were taken for tissue analysis before and after HIIE. p16 INK4a+ cells were located surrounding myofibers in muscle tissues. The maximum decrease in p16 INK4a mRNA levels within muscle tissues occurred at 3 h post-exercise (-82%, p < 0.01), gradually recovering over the next 3-24 h. A concurrent reduction pattern in CD11b mRNA (-87%, p < 0.01) was also found within the same time frame. Ibuprofen treatment attenuated the post-exercise reduction in both p16 INK4a mRNA and CD11b mRNA. The strong correlation (r = 0.88, p < 0.01) between p16 INK4a mRNA and CD11b mRNA in muscle tissues suggests a connection between the markers of tissue aging and pro-inflammatory myeloid differentiation. In conclusion, our results suggest that the senolytic effect of high-intensity exercise on human skeletal muscle is mediated by acute inflammation.

Objectives : To evaluate the effect of intrauterine infusion and hysteroscopic injection of autologous platelet-rich plasma (PRP) in patients with a persistent thin endometrium (EM) undergoing euploid frozen embryo transfer (EFET) cycles. Methods : This prospective case-control study enrolled 116 infertile women with thin EM (<7 mm) who underwent hormone replacement therapy (HRT) for EFET. These women had experienced at least one previous unsuccessful EFET cycle, which either resulted in the cancellation of the cycle or failure of pregnancy. A total of 55 women received an intrauterine infusion of PRP before FET, 38 received a hysteroscopic injection of PRP, and 23 received standard HRT treatment without PRP (control group). Only euploid embryos were transferred in these cycles. The primary outcomes were the implantation rate (IR) and clinical pregnancy rate (CPR) after EFET. Results : After receiving intrauterine infusion and hysteroscopic injection of PRP, 78.2% and 55.3% of patients, respectively, showed an EM thickness exceeding 7 mm, followed by embryo transfer. The hysteroscopic injection group demonstrated significantly higher IR (52%), a higher trend of CPR (52%), and a higher live birth rate (38%) than the control group (18%, 22%, and 4%). Conclusions : Intrauterine infusion and hysteroscopic injection of autologous PRP may be effective methods to increase EM thickness in HRT cycles. According to our results, both methods could increase EM thickness, while hysteroscopic injection appeared to provide more significant assistance in increasing IR, CPR, and live birth rate after EFET in patients with persistent thin EM.

Study Design: Basic research., Objectives: Secreted protein acidic and rich in cysteine (SPARC) is a critical pro-fibrotic mediator. This study aims to characterize the role of SPARC in hypertrophic ligamentum flavum (LF) and fibrosis., Methods: Hypertrophic LF samples were obtained from 8 patients with L4/5 lumbar spinal stenosis (LSS) during the decompressive laminectomy. Non-hypertrophic LF from age- and sex-matched 8 patients with L4/5 lumbar disc herniation was selected as control. An in vitro model of fibrosis in human LF cells was established by interleukin 6 (IL-6) to assess SPARC expression., Results: Hypertrophic LF samples had higher fibrosis scores than control samples by Masson's trichrome staining (3.6 vs. 1.3, P < .001). Hypertrophic LF samples had significantly more positive staining for collagen and SPARC. Collagen III (Col3), α smooth muscle actin (α-SMA), and SPARC mRNA expression levels were significantly higher in hypertrophic LF samples than in control samples by qPCR. SPARC expression and fibrotic and inflammatory makers (collagen I, Col3, IL-6, interleukin 1β) were significantly upregulated in IL-6 stimulation of normal LF in vitro., Conclusion: SPARC was detected in human LF and significantly upregulated in the clinical samples of hypertrophic LF compared to their normal counterparts. We also demonstrated an increased level of SPARC in an in vitro fibrosis model of LF. Thus, SPARC could be a crucial biomarker for the pathogenesis of hypertrophic LF and a therapeutic target for LSS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The immune response of patients with chronic liver disease tends to be lower after receiving their second coronavirus disease 2019 (COVID-19) vaccine dose, but the effect of a third vaccine dose on their immune response is currently unknown. We recruited 722 patients without previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from three hospitals. The patients received homologous (MMM) and heterologous (AZAZBNT, AZAZM) boosters, where AZ, BNT, and M denoted the AZD1222, BNT162b2, and mRNA-1273 vaccines, respectively. Serum IgG spike antibody levels were measured at a mean 1.5 ± 0.7 (visit 1) and 5.0 ± 0.5 (visit 2) months after the third vaccine booster. A threshold of 4160 AU/mL was considered significant antibody activity. In both visits, the patients who received the MMM booster had higher anti-S-IgG levels than those who received the AZAZBNT and AZAZM boosters. Patients with active hepatocellular carcinoma (HCC) had lower anti-S-IgG levels than the control group (761.6 vs. 1498.2 BAU/mL; p = 0.019) at visit 1. The anti-S-IgG levels decreased significantly at visit 2. The patients with significant antibody activity had a lower rate of liver cirrhosis with decompensation (0.7% decompensation vs. 8.0% non-decompensation and 91.3% non-liver cirrhosis, p = 0.015), and active HCC (1.5% active HCC vs. 3.7% non-active HCC and 94.7% non-HCC, p < 0.001). Receiving the MMM booster regimen (OR = 10.67, 95% CI 5.20-21.91, p < 0.001) increased the odds of having significant antibody activity compared with the AZAZBNT booster regimen. Patients with active HCC had a reduced immune response to the third COVID-19 vaccine booster. These findings underscore the importance of booster vaccinations, especially in immunocompromised patients, with superior efficacy observed with the homologous mRNA-1273 regimen., (© 2024 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Background and Aims: Accurate recognition of endoscopic instruments facilitates quantitative evaluation and quality control of endoscopic procedures. However, no relevant research has been reported. In this study, we aimed to develop a computer-assisted system, EndoAdd, for automated endoscopic surgical video analysis based on our dataset of endoscopic instrument images., Methods: Large training and validation datasets containing 45,143 images of 10 different endoscopic instruments and a test dataset of 18,375 images collected from several medical centers were used in this research. Annotated image frames were used to train the state-of-the-art object detection model, YOLO-v5, to identify the instruments. Based on the frame-level prediction results, we further developed a hidden Markov model to perform video analysis and generate heatmaps to summarize the videos., Results: EndoAdd achieved high accuracy (>97%) on the test dataset for all 10 endoscopic instrument types. The mean average accuracy, precision, recall, and F1-score were 99.1%, 92.0%, 88.8%, and 89.3%, respectively. The area under the curve values exceeded 0.94 for all instrument types. Heatmaps of endoscopic procedures were generated for both retrospective and real-time analyses., Conclusions: We successfully developed an automated endoscopic video analysis system, EndoAdd, which supports retrospective assessment and real-time monitoring. It can be used for data analysis and quality control of endoscopic procedures in clinical practice.

Ethnopharmacological Relevance: Erzhi pills (EZP), a traditional Chinese medicine formula prescribed for the treatment of vitiligo, has shown promising efficacy. However, the oral bioactive components and mechanisms underlying the promotion of melanogenesis by EZP remain unclear., Aim of the Study: This study aimed to investigate the pharmacological basis and mechanism of EZP in promoting melanogenesis., Materials and Methods: UHPLC-TOF-MS analysis was used to identify absorbed phytochemicals in serum after oral administration of EZP. Network pharmacology methods were used to predict potential targets and pathways involved in the melanogenic activity of EZP, resulting in the construction of a "compound-target-pathway" network. Zebrafish and B16F10 cells were used to evaluate the effects of EZP on tyrosinase activity and melanin content. Western blot and ELISA analyses were used to validate the effects of EZP on melanogenesis-related proteins, including MITF, TYR, CREB, p-CREB, and cAMP., Results: UHPLC-TOF-MS analysis identified 36 compounds derived from EZP in serum samples. Network pharmacology predictions revealed 89 target proteins associated with the identified compounds and closely related to vitiligo. GO and KEGG analyses indicated the involvement of the cAMP/PKA signaling pathway in the promotion of melanogenesis by EZP. Experimental results showed that EZP increased tyrosinase activity and melanin content in zebrafish and B16F10 cells without inducing toxicity. Western blot and ELISA results suggested that the melanogenic effect of EZP may be related to the activation of the cAMP/PKA signaling pathway. These results confirm the feasibility of combining serum pharmacological and network pharmacological approaches., Conclusions: EZP have the potential to increase tyrosinase activity and melanin content in zebrafish and cells possibly through activation of the cAMP/PKA pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Type 2 diabetes mellitus (T2DM) presents a challenge for individuals today, affecting their health and life quality. Besides its known complications, T2DM has been found to contribute to bone/mineral abnormalities, thereby increasing the vulnerability to bone fragility/fractures. However, there is still a need for appropriate diagnostic approaches and targeted medications to address T2DM-associated bone diseases. This study aims to investigate the relationship between changes in gut microbiota, T2DM, and osteoporosis. To explore this, a T2DM rat model was induced by combining a high-fat diet and low-dose streptozotocin treatment. Our findings reveal that T2DM rats have lower bone mass and reduced levels of bone turnover markers compared to control rats. We also observe significant alterations in gut microbiota in T2DM rats, characterized by a higher relative abundance of Firmicutes (F) and Proteobacteria (P), but a lower relative abundance of Bacteroidetes (B) at the phylum level. Further analysis indicates a correlation between the F/B ratio and bone turnover levels, as well as between the B/P ratio and HbA1c levels. Additionally, at the genus level, we observe an inverse correlation in the relative abundance of Lachnospiraceae . These findings show promise for the development of new strategies to diagnose and treat T2DM-associated bone diseases., Competing Interests: The authors have declared that no competing interests exist.

Background: While global newborn hearing screening programmes (NHSP) are far from the optimal level, the combined hearing and genetic screening has emerged as an innovative approach of early healthcare interventions. There is a clear need for economic evaluation to establish whether newborn deafness gene screening (NDGS), currently mandated by many cities in China, is a good investment., Methods: A decision-tree model was constructed to simulate a hypothetical 10-million Chinese newborn cohort over a lifetime with three strategies: (1) no screening, (2) NHSP (standard screening) and (3) NHSP+NDGS (combined screening). The presence of permanent congenital hearing loss (PCHL) and genetic mutation were assigned at birth and held constant for all strategies. Input parameters were obtained from the Cohort of Deafness-gene Screening study and literature review. The government contract price for genetic screening was US$77/child. Outcomes of interest included the number of early diagnosed PCHL, prelingual deafness, total deafness, special education referral, incremental cost-effectiveness ratio (ICER) and benefit-cost ratio (BCR)., Results: Both standard and combined screening strategies were more effective and more costly than 'no screening'. Compared with standard screening, combined screening led to 9112 (28.0%) more PCHL cases early detected, avoiding 4071 (66.9%) prelingual deafness cases and 3977 (15.6%) special education referrals. The ICER and BCR for combined screening were US$ 4995/disability-adjusted life-year (95% uncertainty interval, 2963 to 9265) and 1.78 (1.19 to 2.39), from healthcare sector perspective. Combined screening would dominate standard screening from societal perspective. Moreover, it remained cost-effective even in pessimistic scenarios., Conclusions: Our findings have particular implication for the 'scale-up' of genetic screening at the national level in China. The model may serve as a feasible example for hearing screening strategies in other countries, as well as genetic screening for other diseases., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. Published by BMJ.)