OBJECTIVE To innovatively apply the pre-intelligent precision dosing and verification system （hereinafter referred to as “the system”）， and to provide a reference for the high-level “intelligent” transformation of inpatient pharmacy. METHODS The limitations of the triple-serial dispensing mode， which comprised the automatic medicine packaging machine （ATC）， intelligent tablet dispensing table （ITDT） and medication detection machine （MDM）， were analyzed. The application of the system and the adoption of the barcode scanning verification method optimized the pre-dosing management， whole-tablet drug dispensing process and ATC temporary dosing management. The comparative analysis was conducted to assess dosing time， labor cost and packaging error of the eight-month period， before and after the system application. RESULTS The triple-serial dispensing mode had a weak ability to avoid error risks in the manual dosing stage， and also had errors in the verification stage. Through the innovative application system， the pre-dosing management had been upgraded， the whole-tablet drug dispensing process had been optimized， and the ATC temporary dosing management had been improved. The average time required for each drug for pre-dosing， whole-tablet drug dispensing and ATC temporary dosing was significantly shortened after the application of the system， compared with before the application of the system （P＜0.001）. The number of pharmacists was reduced from two to one. The error rate of ATC decreased significantly from 0.220‰ to 0.029‰ （P＜0.001）. Specifically， the rate of pharmacist-related errors （pre-dosing error， ITDT dosing error， and ATC temporary dosing error） decreased from 0.116‰ to 0.001‰ （P＜0.001）， and machine-related errors decreased from 0.096‰ to 0.023‰ （P＜0.001）. CONCLUSIONS This innovative integration mode greatly improves the working efficiency and quality of inpatient pharmacy. It enhances refined management of drug expiration and inventory， saves time and labor costs， improves the accuracy of drug dispensing， and ensures patient medication safety.

Thrombospondin 4 (THBS4; TSP4), a crucial component of the extracellular matrix (ECM), serves as an important regulator of tissue homeostasis and various pathophysiological processes. As a member of the evolutionarily conserved thrombospondin family, THBS4 is a multidomain adhesive glycoprotein characterized by six distinct structural domains that mediate its diverse biological functions. Through dynamic interactions with various ECM components, THBS4 plays pivotal roles in cell adhesion, proliferation, inflammation regulation, and tissue remodeling, establishing it as a key modulator of microenvironmental organization. The transcription and translation of THBS4 gene, as well as the activity of the THBS4 protein, are tightly regulated by multiple signaling pathways and extracellular cues. Positive regulators of THBS4 include transforming growth factor-β (TGF-β), interferon-γ (IFNγ), granulocyte-macrophage colony-stimulating factor (GM-CSF), bone morphogenetic proteins (BMP12/13), and other regulatory factors (such as B4GALNT1, ITGA2/ITGB1, PDGFRβ, etc.), which upregulate THBS4 at the mRNA and/or protein level. Conversely, oxidized low-density lipoprotein (OXLDL) acts as a potent negative regulator of THBS4. This intricate regulatory network ensures precise spatial and temporal control of THBS4 expression in response to diverse physiological and pathological stimuli. Functionally, THBS4 acts as a critical signaling hub, influencing multiple downstream pathways essential for cellular behavior and tissue homeostasis. The best-characterized pathways include: (1) the PI3K/AKT/mTOR axis, which THBS4 modulates through both direct and indirect interactions with integrins and growth factor receptors; (2) Wnt/β-catenin signaling, where THBS4 functions as either an activator or inhibitor depending on the cellular context; (3) the suppression of DBET/TRIM69, contributing to its diverse regulatory roles. These signaling connections position THBS4 as a master regulator of cellular responses to microenvironmental changes. Substantial evidence links aberrant THBS4 expression to a range of pathological conditions, including neoplastic diseases, cardiovascular disorders, fibrotic conditions, neurodegenerative diseases, musculoskeletal disorders, and atopic dermatitis. In cancer biology, THBS4 exhibits context-dependent roles, functioning either as a tumor suppressor or promoter depending on the tumor type and microenvironment. In the cardiovascular system, THBS4 contributes to both adaptive remodeling and maladaptive fibrotic responses. Its involvement in fibrotic diseases arises from its ability to regulate ECM deposition and turnover. The diagnostic and therapeutic potential of THBS4 is particularly promising in oncology and cardiovascular medicine. As a biomarker, THBS4 expression patterns correlate significantly with disease progression and patient outcomes. Therapeutically, targeting THBS4-mediated pathways offers novel opportunities for precision medicine approaches, including anti-fibrotic therapies, modulation of the tumor microenvironment, and enhancement of tissue repair. This comprehensive review systematically explores three key aspects of THBS4 research(1) the fundamental biological functions of THBS4 in ECM organization; (2) its mechanistic involvement in various disease pathologies; (3) its emerging potential as both a diagnostic biomarker and therapeutic target. By integrating recent insights from molecular studies, animal models, and clinical investigations, this review provides a framework for understanding the multifaceted roles of THBS4 in health and disease. The synthesis of current knowledge highlights critical research gaps and future directions for exploring THBS4-targeted interventions across multiple disease contexts. Given its unique position at the intersection of ECM biology and cellular signaling, THBS4 represents a promising frontier for the development of novel diagnostic tools and therapeutic strategies in precision medicine.

Direct compression is an ideal method for tablet preparation, but it requires the powder's high functional properties. The functional properties of the powder during compression directly affect the quality of the tablet. 15 parameters such as Py, FES-8KN, FES-12KN, FES-16KN, CR-8KN, CR-12KN, and CR-16KN were used as the characteristic variables in this paper. Unsupervised learning methods like principal component analysis, cluster analysis, and factor analysis were applied to analyze and classify the compression behavior data of 36 traditional Chinese medicine powders. The results showed that both different dimensionality reduction classification methods could effectively differentiate the compression behavior characteristics of 36 traditional Chinese medicine compound powders. The hierarchical cluster analysis results showed a better agreement with the actual compression phenomena of the powders, where group 1 was high elasticity and low compressibility, group 2 was easily compressed and hard to break, group 3 was excellent compressibility and compactibility. This study is expected to provide references and ideas for predicting the behavior of traditional Chinese medicine powders and the screening of tablet formulations.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.