Lei Qin

Objective: This study aimed to investigate the predictive value of preoperative prognostic nutritional index (PNI) and intraoperative modified surgical Apgar score (mSAS) for severe complications (Clavien–Dindo grade ≥ III) after curative-intent surgery in patients with malignant obstructive jaundice (MOJ) and to construct a nomogram prediction model. Methods: The clinical data of 308 patients who underwent curative-intent surgery for MOJ at the First Affiliated Hospital of Soochow University from January 2019 to January 2024 were retrospectively collected. Independent predictive factors were screened using univariate and multivariate logistic regression; the dose–response relationship between PNI and complication risk was analyzed using restricted cubic spline (RCS); subgroup analysis was conducted to evaluate the consistency of predictive effects; procedure-specific sensitivity analyses were performed separately for patients undergoing pancreaticoduodenectomy (PD) and hepatectomy with extrahepatic bile duct resection (HCAE); a nomogram was constructed based on the independent predictive factors, and the performance of the model was evaluated using receiver operating characteristic (ROC), calibration curve, and decision curve analysis (DCA). Results: Among the 308 patients, 65 (21.1%) had severe complications. The PNI (40.30 ± 4.19 vs. 45.91 ± 4.75) and mSAS (5.28 ± 1.28 vs. 7.28 ± 1.34) in the severe complication group were significantly lower than those in the non-severe complication group (all p < 0.001). After multivariable adjustment including surgical approach, higher PNI (OR = 0.73, 95% CI 0.66–0.82, p < 0.001) and higher mSAS (OR = 0.30, 95% CI 0.21–0.44, p < 0.001) were independently associated with lower odds of severe complications. The quartile analysis of PNI showed a graded inverse association (p for trend < 0.001). Multivariable-adjusted RCS analysis demonstrated a significant overall inverse association between PNI and severe complication risk (p for overall < 0.001), with no significant evidence of nonlinearity (p for nonlinearity = 0.425). In procedure-specific sensitivity analyses, the PNI–mSAS model achieved an AUC of 0.959 (95% CI 0.921–0.997) in the PD subgroup and 0.901 (95% CI 0.837–0.965) in the HCAE subgroup. The AUC of the nomogram prediction model was 0.924; the calibration curve indicated good agreement, and DCA suggested potential clinical utility. Conclusion: Preoperative PNI and intraoperative mSAS are independently associated with severe complications after curative-intent surgery in patients with MOJ. The PNI–mSAS nomogram showed good internal discrimination and calibration and may assist perioperative risk stratification; however, external validation is required before routine clinical application.

Microbe‐derived particles (MDPs), which include extracellular vesicles, outer membrane vesicles, inclusion bodies, polysaccharide particles, and virus‐like particles, represent a rapidly expanding category of bioinspired nanomaterials. With their natural origin, intrinsic biocompatibility, and highly programmable functionality, MDPs serve as a versatile bridge between living microbial systems and engineered nanomaterials. This review systematically outlines the diverse classes, biosynthetic pathways, physicochemical properties, and biomedical applications of MDPs. We summarize recent progress in their use for drug delivery, vaccine design, immune modulation, and diagnostic imaging, emphasizing how bioengineering approaches enable precise control over their composition and targeting capabilities. Additionally, we examine advancing methodologies for scalable manufacturing and accurate characterization—such as omics‐based profiling and advanced imaging techniques. Finally, we discuss current challenges and future prospects for integrating synthetic biology with materials science to develop next‐generation intelligent biological platforms based on MDPs. This comprehensive overview aims to foster the rational design and translational deployment of MDP‐based systems across biomedical, biotechnological, and materials science fields.

With the advancement of hydrogel technology, increasing attention has been drawn to hydrogel microspheres (HMs) due to their versatile biomedical applications. HMs play pivotal roles in biomedical applications, such as drug delivery, cell culture, regenerative medicine, wound healing, and tumor immunity. Composed of diverse biobased materials and fabricated through various preparation methods, HMs offer unique structural and functional advantages. This review focuses on the latest findings to provide a more comprehensive understanding of HMs for biomedical applications. Their therapeutic potential across multiple disease contexts is highlighted, and emerging trends and challenges are discussed. By consolidating current knowledge, this work aims to inspire further research and accelerate the clinical translation of HMs.

Tim-1 (T-cell immunoglobulin and mucin domain 1), also known as Kim-1 (kidney injury molecule 1) or hepatitis A virus cellular receptor 1 (HAVCR1), is a transmembrane protein expressed on various immune and epithelial cells. It plays a role in modulating inflammatory and immune responses. In this study, we find that Tim-1 is overexpressed in hepatocellular carcinoma (HCC) samples and that its expression is significantly correlated with postoperative survival. Bulk RNA sequencing reveals a general upregulation of extracellular matrix-related genes in HCC tissues with Tim-1 overexpression. The results of the cell and in vivo experiments reveal that Tim-1 in HCC not only affects biological processes such as the proliferation, migration, and invasion of HCC cells but also broadly promotes extracellular matrix processes by influencing cytokine secretion. Further studies demonstrate that Tim-1 mediates the activation of hepatic stellate cells and upregulates Th1 and Th2 cytokines, thereby promoting HCC progression. Thus, Tim-1 may represent a novel target for future interventions in HCC and liver fibrosis.

Objectives: To investigate the impact of combining lenvatinib with transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC). Methods: This was a retrospective observational study which reviewed the medical records of 103 unresectable HCC patients from January 2017 to June 2020 in The First Affiliated Hospital of Soochow University. It included 46 patients who received TACE plus lenvatinib and 57 patients who received TACE alone. The levels of serum indicators, clinical effect, adverse events, overall survival (OS), and progression-free survival (PFS) were compared between the two groups. Results: AFP and VEGF levels in the TACE+lenvatinib group post-treatment were significantly lower than the TACE group (P<0.05). The clinical efficacy in the TACE+lenvatinib group (69.57%) was higher than that in the TACE group (40.35%) post-treatment (P<0.05). There were significant differences in hypertension, diarrhea, and bleeding (gingiva) between the two groups (P0.05), while the two years survival rate in the TACE+lenvatinib group was significantly higher than that in the TACE group (P<0.05). Conclusions: TACE combined with lenvatinib have a high clinical effective rate, with reduced AFP and VEGF levels, higher two year survival rate, and acceptable incidence of adverse events. doi: https://doi.org/10.12669/pjms.39.6.7944 How to cite this: Long J, Liu L, Yang X, Lu X, Qin L. Impact of combining Lenvatinib with Transarterial chemoembolization for unresectable hepatocellular carcinoma. Pak J Med Sci. 2023;39(6):1847-1852. doi: https://doi.org/10.12669/pjms.39.6.7944 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This study aimed to investigate the role of the long non-coding RNA (lncRNA) LINC00342-207 (LINC00342) in the development and progression of primary hepatocellular carcinoma (HCC). Forty-two surgically resected HCC tissues and corresponding paracancerous tissues were collected from October 2019 to December 2020 and examined for lncRNA LINC00342, microRNA (miR)-19a-3p, miR-545-5p, miR-203a-3p, cell cycle protein D1 (CyclinD1/CCND1), murine double minute 2 (MDM2), and fibroblast growth factor 2 (FGF2) expression. The disease-free survival and overall survival of patients with HCC were followed up. HCC cell lines and the normal hepatocyte cell line HL-7702 were cultured and the expression level of LINC00342 was measured. HepG2 cells were transfected with LINC00342 siRNA, LINC00342 overexpression plasmid, miR-19a-3p mimics and their corresponding suppressors, miR-545-5p mimics and their corresponding suppressors, and miR-203a-3p mimics and their corresponding suppressors. The proliferation, apoptosis, migration, and invasion of HepG2 cells were detected. Stably transfected HepG2 cells were inoculated into the left axilla of male BALB/c nude mice, and the volume and quality of transplanted tumors as well as the expression levels of LINC00342, miR-19a-3p, miR-545-5p, miR-203a-3p, CCND1, MDM2, and FGF2 were examined. LINC00342 played an oncogenic role in HCC and exhibited inhibitory effects on proliferation, migration, and invasion, and promoted the apoptosis of HepG2 cells. Moreover, it inhibited the growth of transplanted tumors in vivo in mice. Mechanistically, the oncogenic effect of LINC00342 was associated with the targeted regulation of the miR-19a-3p/CCND1, miR-545-5p/MDM2, and miR-203a-3p/FGF2 axes.

Metastasis is an important factor contributing to poor prognosis in patients with gastric cancer; yet, the molecular mechanism leading to this cell behavior is still not well understood. In this study, we explored the role of cysteine protease inhibitor SN (Cystatin SN, CST1) in promoting gastric cancer metastasis. We hypothesized that CST1 could regulate gastric cancer progression by regulating GPX4 and ferroptosis. Whole transcriptome sequencing suggested that the expression of CST1 was significantly increased in metastatic cancer, and high CST1 expression was correlated with a worse prognosis. Our data further confirmed that the overexpression of CST1 may significantly promote the migration and invasion of gastric cancer cells in vitro and enhance liver, lung, and peritoneal metastasis of gastric cancer in nude mice. Meanwhile, high expression of CST1 promoted the epithelial-mesenchymal transition (EMT) of gastric cancer cells. Mechanistically, a co-immunoprecipitation experiment combined with mass spectrometry analysis confirmed that CST1 could interact with GPX4, a key protein regulating ferroptosis. CST1 relieves GPX4 ubiquitination modification by recruiting OTUB1, improving GPX4 protein stability and reducing intracellular reactive oxygen species (ROS), thereby inhibiting ferroptosis and, in turn, promoting gastric cancer metastasis. Moreover, clinical data suggested that CST1 is significantly increased in peripheral blood and ascites of gastric cancer patients with metastasis; multivariate Cox regression model analysis showed that CST1 was an independent risk factor for the prognosis of gastric cancer patients. Overall, our results elucidated a critical pathway through which high CST1 expression protects gastric cancer cells from undergoing ferroptosis, thus promoting its progression and metastasis. CST1 may be used as a new oncological marker and potential therapeutic target for gastric cancer metastasis.

Emerging evidence has uncovered that noncoding RNAs (ncRNAs) contribute to the development of hepatocellular carcinoma (HCC). Nevertheless, the functions of the majority of long ncRNAs (lncRNAs) in HCC are unknown. Here, we intend to probe the function of lncRNA NUTM2A-AS1 in the evolvement of HCC and the related mechanism. Expression levels of lncRNA NUTM2A-AS1, miR-186-5p and KLF7 mRNA in HCC tissues and adjacent non-tumor tissues were monitored. Gain- or loss-of-function assays were utilized to investigate the biological functions of lncRNA NUTM2A-AS1, miR-186-5p and KLF7 in HCC cell lines (including HCCLM3 and Huh7). Western blot was implemented for the detection of the epithelial–mesenchymal transition (EMT)-related proteins (including E-cadherin, Vimentin and Snail), KLF7, Wnt, β-catenin, and stemness-related proteins (Nanog, OCT4, YKL40, and CD133). Furthermore, the targeted associations between lncRNA NUTM2A-AS1, miR-186-5p, and KLF7 were verified by bioinformatics analysis, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. As a result, lncRNA NUTM2A-AS1 and KLF7 profiles were heightened in the HCC tissues versus adjacent normal tissues, while miR-186-5p had the opposite expression tendency. Up-regulation of lncRNA NUTM2A-AS1 was related to tumor size, advanced tumor stage, and lymph node metastasis of HCC patients. Functionally, overexpression of lncRNA NUTM2A-AS1 heightened HCC cells’ growth, invasion, EMT, and stemness and repressed their apoptosis by activating the Wnt/β-catenin pathway. In contrast, up-regulation of miR-186-5p or inhibition of KLF7 had reverse effects. In vivo, lncRNA NUTM2A-AS1 overexpression facilitated tumor growth and EMT, accompanied by declined miR-186-5p levels and enhanced KLF7 expression. The mechanistic studies revealed that miR-186-5p served as a common target of lncRNA NUTM2A-AS1 and KLF7. As hinted by the rescue experiments, NUTM2A-AS1 partly abated miR-186-5p-mediated anti-tumor effects in HCC cells, whereas KLF7 knockdown reversed the promotive effects of NUTM2A-AS1. LncRNA NUTM2A-AS1 accelerated the evolution of HCC by up-regulating the KLF7/Wnt/beta-catenin pathway through sponging miR-186-5p.