A protracted war against cancer drug resistance.

Currently, even the most effective anti-cancer therapies are often limited by the development of drug resistance and tumor relapse, which is a major challenge facing current cancer research. A deep understanding of the molecular and biochemical bases of drug efficacy that can help predict the clinical drug resistance, coupled with the evolution of systematic genomic and proteomic technologies, have facilitated studies identifying and elucidating the underlying mechanisms. In this review, we focus on several important issues on cancer drug resistance and provide a framework for understanding the common ways by which cancers develop resistance to therapeutic agents. With the increasing arsenal of novel anticancer agents and techniques, there are now unprecedented opportunities to understand and overcome drug resistance. The proteolysis targeting chimera (PROTAC) technology, immunotherapy, nanomedicine, and real-time monitoring of drug response all provide effective approaches for combating drug resistance. In addition to the advancement of therapeutic technologies, the revolution of treatment concept is also of great importance. We can take advantage of the interplay between drug sensitive and resistant subclones for combating cancer. However, there remains a long way to go in the protracted war against cancer drug resistance.

Polydatin ameliorates early brain injury after subarachnoid hemorrhage through up-regulating SIRT1 to suppress endoplasmic reticulum stress.

Objective: This study aims to investigate the inhibitory effect of Polydatin (PD) on endoplasmic reticulum (ER) stress following subarachnoid hemorrhage (SAH) and to elucidate the underlying mechanisms. Methods: A standard intravascular puncture model was established to mimic SAH in mice. Neurological functions were assessed using neurological scoring, Grip test, and Morris water maze. Brain edema and Evans blue extravasation were measured to evaluate blood-brain barrier permeability. Western blot and quantitative real-time polymerase chain reaction (PCR) analyses were performed to examine protein and mRNA expressions related to ER stress. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was used to detect cell apoptosis, and transmission electron microscopy was used to observe the ultrastructure of the endoplasmic reticulum. Results: The results indicated that PD significantly reduced brain edema and Evans blue extravasation after SAH, improving neurological function. Compared to the SAH group, the expression levels of ER stress-related proteins including glucose-regulated protein 78 (GRP78), phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were significantly lower in the PD-treated group. Moreover, PD significantly enhances the protein expression of Sirtuin 1 (SIRT1). Validation with sh-SIRT1 confirmed the critical role of SIRT1 in ER stress, with PD's inhibitory effect on ER stress being dependent on SIRT1 expression. Additionally, PD attenuated ER stress-mediated neuronal apoptosis and SAH-induced ferroptosis through upregulation of SIRT1. Conclusion: PD alleviates ER stress following SAH by upregulating SIRT1 expression, thereby mitigating early brain injury. The protective effects of PD are mediated through SIRT1, which inhibits ER stress and reduces neuronal apoptosis and ferroptosis.

Endoscopic dacryocystorhinostomy in acute dacryocystitis: a multicenter study in China.

AIM: To report the clinical profile, endoscopic dacryocystorhinostomy (En-DCR) management, and acute dacryocystitis (AD) outcomes in China. METHODS: Clinical data of 554 adult AD patients (554 eyes) who presented in 7 tertiary eye care centers for 10y from Jan 2010 to Mar 2020 were retrospectively analyzed. Clinical profile, En-DCR management, and outcomes of all cases were recorded. The anatomical and functional success were evaluated for 12mo post-operation. RESULTS: The analysis included 149 males and 368 females with a median age of 55.2y (range: 18-84y). There were 459 eyes with a history of epiphora or purulent secretion. The time between a symptom of lacrimal duct obstruction and acute onset was 1 to 540 (66.1±58.2)mo. Fifty-nine eyes had a history of the previous acute attack. Seventy-four eyes developed a cutaneous fistula, while 11 eyes had post septal cellulitis pre-operation. En-DCR with an anatomical success of 91.7% and functional success of 90.1%. The success rate of the patients with a history of acute episodes and the preoperative fistula was lower than the overall success rates. CONCLUSION: En-DCR can be performed during an acute episode in AD with a success rate of over 90%.

Advances in the understanding of the role and mechanism of action of PFKFB3­mediated glycolysis in liver fibrosis (Review).

Liver fibrosis is a pathophysiologic manifestation of chronic liver disease and a precursor to cirrhosis and hepatocellular carcinoma. Glycolysis provides intermediate metabolites as well as energy support for cell proliferation and phenotypic transformation in liver fibers. 6­Phosphofructo­2­kinase/fructose­2,6­bisphosphatase 3 (PFKFB3) is a key activator of glycolysis and plays an important role in the process of glycolysis. The role of PFKFB3­mediated glycolysis in myocardial fibrosis, renal fibrosis and pulmonary fibrosis has been demonstrated, and the role of PFKFB3 in the activation of hepatic stellate cells by aerobic glycolysis has been proven by relevant experiments. The present study reviews the research progress on the role and mechanism of action of PFKFB3­mediated glycolysis in the progression of hepatic fibrosis to discuss the role of PFKFB3­mediated glycolysis in hepatic fibrosis and to provide new ideas for research on PFKFB3 as a target for the treatment of hepatic fibrosis.

S2P-Matching: Self-supervised Patch-based Matching Using Transformer for Capsule Endoscopic Images Stitching.

The Magnetically Controlled Capsule Endoscopy (MCCE) has a limited shooting range, resulting in capturing numerous fragmented images and an inability to precisely locate and examine the region of interest (ROI) as traditional endoscopy can. Addressing this issue, image stitching around the ROI can be employed to aid in the diagnosis of gastrointestinal (GI) tract conditions. However, MCCE images possess unique characteristics, such as weak texture, close-up shooting, and large angle rotation, presenting challenges to current image-matching methods. In this context, a method named S2P-Matching is proposed for self-supervised patch-based matching in MCCE image stitching. The method involves augmenting the raw data by simulating the capsule endoscopic camera's behavior around the GI tract's ROI. Subsequently, an improved contrast learning encoder is utilized to extract local features, represented as deep feature descriptors. This encoder comprises two branches that extract distinct scale features, which are combined over the channel without manual labeling. The data-driven descriptors are then input into a Transformer model to obtain patch-level matches by learning the globally consented matching priors in the pseudo-ground-truth match pairs. Finally, the patch-level matching is refined and filtered to the pixel-level. The experimental results on real-world MCCE images demonstrate that S2P-Matching provides enhanced accuracy in addressing challenging issues in the GI tract environment with image parallax. The performance improvement can reach up to 203 and 55.8% in terms of NCM (Number of Correct Matches) and SR (Success Rate), respectively. This approach is expected to facilitate the wide adoption of MCCE-based gastrointestinal screening.

Positioning exercises in improving the quality of magnetic-controlled capsule endoscopy.

BACKGROUND: Good gastric preparation is indispensable for Magnetic-controlled Capsule Endoscopy (MCE) examination, but there is no consensus yet. We aim to explore the clinical application value of positioning exercises in improving the quality of MCE examination. METHODS: Clinical data of 326 patients who underwent MCE examination from January 2020 to December 2023 were collected. The included patients were divided into two groups: the conventional medication preparation group (CMP group, accepted mucosal cleansing medication only) and the positioning exercises group (PE group, accepted mucosal cleansing medication plus positioning exercises). A comparison was made between the two groups in terms of gastric cavity cleanliness score, visibility score, and detection rate of positive lesions. RESULTS: The examination time was (21.29 ± 5.82) minutes in the PE group and (30.54 ± 6.37) minutes in the CMP group, showing a significant difference between the two groups (P < 0.001). The total cleanliness score and visibility score in the CMP group were 15.89 ± 2.82 and 10.93 ± 2.12, respectively. In contrast, the total cleanliness score and visibility score in the PE group were 19.52 ± 2.26 and 15.09 ± 2.31, respectively. The PE group showed significantly better cleanliness scores and visibility scores in all six anatomical regions compared to the CMP group (All P < 0.001). However, there was no significant difference in the detection rate of positive lesions between the two groups (All P > 0.05). CONCLUSION: Positioning exercises before MCE examination can improve the quality of gastric mucosal images and reduce the duration of the examination for patients.

Combination of radiotherapy and PD-L1 blockade induces abscopal responses in EGFR-mutated lung cancer through activating CD8+ T cells.

Patients with EGFR-mutated non-small cell lung cancer (NSCLC) respond poorly to immune checkpoint inhibitors (ICIs). It has been reported that the number of CD8+T cells is reduced in EGFR-mutated NSCLC. However, the extent of heterogeneity and effector function of distinct populations of CD8+T cells has not been investigated intensively. In addition, studies investigating whether a combination of radiotherapy and ICIs can improve the efficacy of ICIs in EGFR-mutated lung cancer are lacking. Single-cell RNA sequencing (scRNA-seq) was used to investigate the heterogeneity of CD8+T cell populations in EGFR-mutated NSCLC. The STING pathway was explored after hypofractionated radiation of EGFR-mutated and wild-type cells. Mice bearing LLC-19del and LLC-EGFR tumors were treated with radiotherapy plus anti-PD-L1. The scRNA-seq data showed the percentage of progenitor exhausted CD8+T cells was lower in EGFR-mutated NSCLC. In addition, CD8+T cells in EGFR-mutated NSCLC were enriched in oxidative phosphorylation. In EGFR-mutated and wild-type cells, 8 Gy × 3 increased the expression of chemokines that recruit T cells and activate the cGAS-STING pathway. In the LLC-19del and LLC-EGFR mouse model, the combination of radiation and anti-PD-L1 significantly inhibited the growth of abscopal tumors. The enhanced abscopal effect was associated with systemic CD8+T cell infiltration. This study provided an intensive understanding of the heterogeneity and effector functions of CD8+T cells in EGFR-mutated NSCLC. We showed that the combination of hypofractionated radiation and anti-PD-L1 significantly enhanced the abscopal responses in both EGFR-mutated and wild-type lung cancer by activating CD8+T cells in mice.

Tumor perfusion enhancement by microbubbles ultrasonic cavitation reduces tumor glycolysis metabolism and alleviate tumor acidosis.

The tumor microenvironment is increasingly acknowledged as a critical contributor to cancer progression, mediating genetic and epigenetic alterations. Beyond diverse cellular interactions from the microenvironment, physicochemical factors such as tumor acidosis also significantly affect cancer dynamics. Recent research has highlighted that tumor acidosis facilitates invasion, immune escape, metastasis, and resistance to therapies. Thus, noninvasive measurement of tumor acidity and the development of targeted interventions represent promising strategies in oncology. Techniques like contrast-enhanced ultrasound (CEUS) can effectively assess blood perfusion, while ultrasound-stimulated microbubble cavitation (USMC) has proven to enhance tumor blood perfusion. We therefore aimed to determine whether CEUS assesses tumor acidity and whether USMC treatment can modulate tumor acidity. Firstly, we tracked CEUS perfusion parameters in MCF7 tumor models and compared them with in vivo tumor pH recorded by pH microsensors. We found that the peak intensity and area under curve of tumor contrast-enhanced ultrasound correlated well with tumor pH. We further conducted USMC treatment on MCF7 tumor-bearing mice, tracked changes of tumor blood perfusion and tumor pH in different perfusion regions before and after the USMC treatment to assess its impact on tumor acidity and optimize therapeutic ultrasound pressure. We discovered that USMC with 1.0 Mpa significantly improved tumor blood perfusion and tumor pH. Furthermore, tumor vascular pathology and PGI2 assays indicated that improved tumor perfusion was mainly due to vasodilation rather than angiogenesis. More importantly, analysis of glycolysis-related metabolites and enzymes demonstrated USMC treatment can reduce tumor acidity by reducing tumor glycolysis. These findings support that CEUS may serve as a potential biomarker to assess tumor acidity and USMC is a promising therapeutic modality for reducing tumor acidosis.

A hybrid RSM-BPNN-GA approach for optimizing ultrasound-assisted deep eutectic solvents extraction conditions for Mesona chinensis benth. and investigation of the extraction mechanism.

Mesona chinensis Benth (MCB) is the source of the most commonly consumed herbal beverage in Southeast Asia and China and is thus an economically important agricultural plant. Therefore, optimal extraction and production procedures have significant commercial value. Currently, in terms of green chemistry, researchers are investigating the use of greener solvents and innovative extraction techniques to increase extract yields. This study represents the first investigation of the optimal conditions for ultrasound-assisted deep eutectic solvent (DES) extraction from MCB. The major factors influencing ultrasound-assisted DESs were optimized using the response surface methodcentral-genetic algorithm-back propagation neural networks. This model demonstrated superior predictability and accuracy compared to the RSM model. Various types of DESs were used for the extraction of MCB constituents, with choline chloride-ethylene glycol resulting in the highest yield. The optimal conditions for maximal extraction were the use of choline chloride-ethylene glycol (1:4) as the solvent with a 40% water content, an extraction duration of 60 min at 60°C, and maintaining a leaf-to-solvent ratio of 20 mL/g. Noticeable enhancements in Van der Waals forces and more robust interactions between DESs and the target chemicals were observed relative to those seen with ethanol (70%, v/v) or water. This investigation not only introduced an environmentally friendly approach for highly efficient extraction from MCB but also identified the mechanisms underlying the improved extraction efficacy. These findings have the potential to contribute to the broader utilization of MCB and provide valuable insights into the extraction mechanisms utilizing deep eutectic solvents. PRACTICAL APPLICATION: This work describes an efficient and green ultrasound-assisted deep eutectic solvent (DES) method for Mesona chinensis Benth (MCB) extraction. Molecular dynamics was used to examine the intermolecular interactions between the solvent and the extracted compounds. It is anticipated that green and environmentally friendly solvents, such as DESs, will be used in further research on foods and their bioactive components. With the development of the herbal tea industry, new products made of MCB are becoming increasingly popular, thus gradually making it a research hotspot.

Beautoide A, an Anti-Osteoclastogenic Steroid from Beauveria sp. NBUF147 Associated with an Irciniidae Sponge from the Marine Mesophotic Zone.

Mesophotic coral ecosystems (MCEs), located at depths ranging from 30-150 m, host some of the most diverse yet least explored marine bioresources, particularly significant for the discovery of new bioactive molecules. The fungus Beauveria sp. NBUF147, associated with an Irciniidae sponge from the mesophotic zone at a depth of 82 m, underwent chemical investigation that led to the identification of one new sterol, beautoide A (1), and one reported sterol, 3ß,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (2). Their structures were determined from analysis of spectroscopic data and X-ray crystallography. Evaluation of biological activity in prednisolone-induced osteoporotic zebrafish showed that 1 was anti-osteoclastogenic in vivo at 3.0 µM.

Strengthening gold with dispersed nanovoids.

Materials often fail prematurely or catastrophically under load while containing voids, posing a challenge to materials manufacturing. We found that a metal (gold) containing spherical voids with a fraction of up to 10% does not fracture prematurely in tension when the voids are shrunk to the submicron or nanometer scale. Instead, the dispersed nanovoids increase the strength and ductility of the material while simultaneously reducing its weight. Apart from the suppressed stress or strain concentration, such structure provides enormous surface area and promotes surface-dislocation interactions, which enable strengthening and additional strain hardening and thus toughening. Transforming voids from crack-like detrimental defects into a beneficial "ingredient" provides an inexpensive and environmentally friendly approach for the development of a new class of lightweight, high-performance materials.

S100a8/a9 regulated by LPS/TLR4 axis plays an important role in Salmonella-based tumor therapy and host defense.

Bacteria are ideal anticancer agents and carriers due to their unique capabilities that are convenient in genetic manipulation, tumor-specific targeting, and deep-tissue penetration. However, the specific molecular mechanisms of bacteria-mediated cancer therapy (BMCT) have not been clarified. In this study, we found that TLR4 signaling pathway is critical for Salmonella-mediated tumor targeting, tumor suppression, and liver and spleen protection. TLR4 knockout in mice decreased the levels of cytokines and chemokines, such as S100a8, S100a9, TNF-α, and IL-1ß, in tumor microenvironments (TMEs) after Salmonella treatment, which inhibited tumor cell death and nutrient release, led to reduced bacterial contents in tumors and attenuated antitumor efficacy in a negative feedback manner. Importantly, we found that S100a8 and S100a9 played a leading role in Salmonella-mediated cancer therapy (SMCT). The antitumor efficacy was abrogated and liver damage was prominent when blocked with a specific inhibitor. These findings elucidated the mechanism of Salmonella-mediated tumor targeting, suppression, and host antibacterial defense, providing insights into clinical cancer therapeutics.

Blocking ACSL6 Compromises Autophagy via FLI1-Mediated Downregulation of COLs to Radiosensitize Lung Cancer.

Lung cancer (LC) is the leading cause of cancer-related mortality worldwide. Radiotherapy is the main component of LC treatment; however, its efficacy is often limited by radioresistance development, resulting in unsatisfactory clinical outcomes. Here, we found that LC radiosensitivity is up-regulated by decreased expression of long-chain acyl-CoA synthase 6 (ACSL6) after irradiation. Deletion of ACSL6 results in significant elevation of Friend leukemia integration 1 transcription factor (FLI1) and a marked decline of collagens (COLs). Blocking of ACSL6 impairs the tumor growth and upregulates FLI1, which reduces the levels of COLs and compromises irradiation-induced autophagy, leading to considerable therapeutic benefits during radiotherapy. Moreover, the direct interaction between ACSL6 and FLI1 and engagement between FLI1 and COLs indicates the involvement of the ACSL6-FLI1-COL axis. Finally, the potently adjusted autophagy flux reduces its otherwise contributive capability in surviving irradiation stress and leads to satisfactory radiosensitization for LC radiotherapy. These results demonstrate that enhanced ACSL6 expression promotes the aggressive performance of irradiated LC through increased FLI1-COL-mediated autophagy flux. Thus, the ACSL6-FLI1-Col-autophagy axis may be targeted to enhance the radiosensitivity of LC and improve the management of LC in radiotherapy.

Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction.

While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for detection of molecular residual disease (MRD), its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read-level, achieving an error rate of 4.2 × 10-7, which is about two orders of magnitude lower than a read-centric de-noising method. The application of AccuScan to MRD demonstrated analytical sensitivity down to 10-6 circulating variant allele frequency at 99% sample-level specificity. AccuScan showed 90% landmark sensitivity (within 6 weeks after surgery) and 100% specificity for predicting relapse in colorectal cancer. It also showed 67% sensitivity and 100% specificity in esophageal cancer using samples collected within one week after surgery. When AccuScan was applied to monitor immunotherapy in melanoma patients, the circulating tumor DNA (ctDNA) levels and dynamic profiles were consistent with clinical outcomes. Overall, AccuScan provides a highly accurate WGS solution for MRD detection, empowering ctDNA detection at parts per million range without requiring high sample input or personalized reagents.

The Impact of Novel BMPR1B Mutations on Litter Size in Short-Tailed Gobi Sheep and Larger-Tailed Ujimqin Sheep.

The significant deposition of tail fat in sheep has a profound impact on the economic benefits of animal husbandry. Furthermore, increasing the litter size is a crucial means of enhancing economic benefits. The BMPR1B and T/Brachyury genes are considered major functional genes that could affect sheep litter size and tail bone number, respectively. In this study, we employed direct sequencing to identify specific mutations of the BMPR1B gene in Gobi short tail sheep and carried out genotyping using MassARRAY technology for each variant of both the BMPR1B and T genes. Significant associations were demonstrated between the c.687G>A mutation of BMPR1B and the litter size in both the Gobi short tail sheep and Ujimqin sheep breeds. Meanwhile, the g.30058882_30058873GCAGATTAAAIndel mutation was significantly associated with the litter size in Gobi short tail sheep. These findings may provide valuable genetic markers for expanding sheep litter size. In addition, we also confirmed that the frequency of tail-bone-number-related T alleles was significantly higher in Gobi short tail sheep than in longer-tailed Ujimqin sheep.

Systematic characterization of the expression, prognosis and immune characteristics of PLOD family genes in breast cancer.

BACKGROUND: The expression patterns and prognostic value of Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family genes in breast cancer remain to be elucidated. METHODS: The expression levels, prognostic value, and biological function of PLODs were determined using Oncomine, cBioPortal, GEPIA, Timer, UALCAN, PrognoScan, GeneMANIA, Metascape, and breast cancer tissue microarrays. RESULTS: The expressions of PLOD1 and PLOD3 were upregulated in breast cancer tissues, indicating worse clinical stages. High expression levels of PLOD family genes were associated with worse disease-free survival and distant metastasis-free survival, while high expression levels of PLOD1 and PLOD3 were related to worse overall survival in all breast cancer patients. The levels of PLOD family genes were all significantly higher in the age ≤51 y group, HR-negative patients, and triple negative breast cancer (TNBC) patients. They are associated with tumor-infiltrating immune cells (TIICs), including CD4+ T cells, CD8+ T cells, B cells, macrophages, neutrophils, and dendritic cells. According to co-expression gene analysis and functional enrichment, they are associated with protein hydroxylation, collagen biosynthesis and modifying enzymes, collagen metabolism, RNA splicing, extracellular matrix organization, VEGFA-VEGFR2 signaling pathway, and skeletal system development. Immunohistochemistry showed that the expressions of all PLOD family genes were significantly elevated in breast cancer tissues. PLOD1 expression was positively correlated with ER, TNBC status, and tumor grade. PLOD2 expression was positively connected with Ki-67 status. PLOD3 expression was positively related with age and tumor grade. CONCLUSIONS: PLOD family genes are novel potential prognostic biomarkers for breast cancer, and targeting PLOD inhibitors might be an effective strategy for breast cancer therapy.

Genetic evidence for a causal link between gut microbiota and arterial embolism and thrombosis: a two-sample Mendelian randomization study.

Background: Previous research has hinted at a crucial link between gut microbiota and arterial embolism and thrombosis, yet the causal relationship remains enigmatic. To gain a deeper understanding, we aimed to comprehensively explore the causal relationship and elucidate the impact of the gut microbiota on the risk through a two-sample Mendelian randomization (MR) study. Methods: Genetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics for IBS were drawn from a GWAS including 1,076 cases and 381,997 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test. Results: We identified three bacterial traits that were associated with the risk of arterial embolism and thrombosis: odds ratio (OR): 1.58, 95% confidence interval (CI): 1.08-2.31, p = 0.017 for genus Catenibacterium; OR: 0.64, 95% CI: 0.42-0.96, p = 0.031 for genus Dialister; and OR: 2.08, 95% CI: 1.25-3.47, p = 0.005 for genus Odoribacter. The results of sensitivity analyses for these bacterial traits were consistent (P<0.05). Conclusion: Our systematic analyses provided evidence to support a potential causal relationship between several gut microbiota taxa and the risk of arterial embolism and thrombosis. More studies are required to show how the gut microbiota affects the development of arterial embolism and thrombosis.

The role and mechanism of pyroptosis and potential therapeutic targets in non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome characterized by the excessive accumulation of fat within liver cells, which can progress to end-stage liver disease in severe cases, posing a threat to life. Pyroptosis is a distinct, pro-inflammatory form of cell death, differing from traditional apoptosis. In recent years, there has been growing research interest in the association between pyroptosis and NAFLD, encompassing the mechanisms and functions of pyroptosis in the progression of NAFLD, as well as potential therapeutic targets. Controlled pyroptosis can activate immune cells, eliciting host immune responses to shield the body from harm. However, undue activation of pyroptosis may worsen inflammatory responses, induce cellular or tissue damage, disrupt immune responses, and potentially impact liver function. This review elucidates the involvement of pyroptosis and key molecular players, including NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome, gasdermin D (GSDMD), and the caspase family, in the pathogenesis and progression of NAFLD. It emphasizes the promising prospects of targeting pyroptosis as a therapeutic approach for NAFLD and offers valuable insights into future directions in the field of NAFLD treatment.

Biomechanical analysis of an absorbable material for treating fractures of the inferior orbital wall.

AIM: To investigate the biomechanical properties and practical application of absorbable materials in orbital fracture repair. METHODS: The three-dimensional (3D) model of orbital blowout fractures was reconstructed using Mimics21.0 software. The repair guide plate model for inferior orbital wall fracture was designed using 3-matic13.0 and Geomagic wrap 21.0 software. The finite element model of orbital blowout fracture and absorbable repair plate was established using 3-matic13.0 and ANSYS Workbench 21.0 software. The mechanical response of absorbable plates, with thicknesses of 0.6 and 1.2 mm, was modeled after their placement in the orbit. Two patients with inferior orbital wall fractures volunteered to receive single-layer and double-layer absorbable plates combined with 3D printing technology to facilitate surgical treatment of orbital wall fractures. RESULTS: The finite element models of orbital blowout fracture and absorbable plate were successfully established. Finite element analysis (FEA) showed that when the Young's modulus of the absorbable plate decreases to 3.15 MPa, the repair material with a thickness of 0.6 mm was influenced by the gravitational forces of the orbital contents, resulting in a maximum total deformation of approximately 3.3 mm. Conversely, when the absorbable plate was 1.2 mm thick, the overall maximum total deformation was around 0.4 mm. The half-year follow-up results of the clinical cases confirmed that the absorbable plate with a thickness of 1.2 mm had smaller maximum total deformation and better clinical efficacy. CONCLUSION: The biomechanical analysis observations in this study are largely consistent with the clinical situation. The use of double-layer absorbable plates in conjunction with 3D printing technology is recommended to support surgical treatment of infraorbital wall blowout fractures.

Pathophysiological role of ion channels and transporters in hepatocellular carcinoma.

The incidence of hepatocellular carcinoma (HCC) has continued to increase annually worldwide, and HCC has become a common cause of cancer-related death. Despite great progress in understanding the molecular mechanisms underlying HCC development, the treatment of HCC remains a considerable challenge. Thus, the survival and prognosis of HCC patients remain extremely poor. In recent years, the role of ion channels in the pathogenesis of diseases has become a hot topic. In normal liver tissue, ion channels and transporters maintain water and electrolyte balance and acid‒base homeostasis. However, dysfunction of these ion channels and transporters can lead to the development and progression of HCC, and thus these ion channels and transporters are expected to become new therapeutic targets. In this review, ion channels and transporters associated with HCC are reviewed, and potential targets for new and effective therapies are proposed.