The fundamental principles for treating ankle fractures, as with other intra-articular fractures, are anatomical reduction and stable internal fixation. Despite successful reduction, between 14% and 40% of patients continue to experience persistent pain or unsatisfactory functional outcomes. Furthermore, approximately 1% of patients progress to post-traumatic arthritis, necessitating further surgical intervention. Ankle fractures are frequently accompanied by intra-articular injuries, including osteochondral lesions, ligament tears, and syndesmosis injuries. Arthroscopy is becoming increasingly prevalent in managing acute ankle fractures by assessing intra-articular damage and facilitating accurate reduction. This review examined the role and indications for arthroscopy in ankle fractures, particularly emphasizing its benefits in diagnosing and managing associated injuries, including osteochondral lesions, syndesmosis, and deltoid ligament injuries. Furthermore, arthroscopy facilitates fracture reduction, offering a minimally invasive approach with a shorter recovery period and enhanced visualization. Its use extends to pediatric fractures and complex cases such as Maisonneuve and calcaneal fractures, potentially improving outcomes while minimizing complications. Understanding the evolving indications and benefits of arthroscopy for ankle fractures can lead to improved clinical outcomes and reduced complications.

The fundamental principles for treating ankle fractures, as with other intra-articular fractures, are anatomical reduction and stable internal fixation. Despite successful reduction, between 14% and 40% of patients continue to experience persistent pain or unsatisfactory functional outcomes. Furthermore, approximately 1% of patients progress to post-traumatic arthritis, necessitating further surgical intervention. Ankle fractures are frequently accompanied by intra-articular injuries, including osteochondral lesions, ligament tears, and syndesmosis injuries. Arthroscopy is becoming increasingly prevalent in managing acute ankle fractures by assessing intra-articular damage and facilitating accurate reduction. This review examined the role and indications for arthroscopy in ankle fractures, particularly emphasizing its benefits in diagnosing and managing associated injuries, including osteochondral lesions, syndesmosis, and deltoid ligament injuries. Furthermore, arthroscopy facilitates fracture reduction, offering a minimally invasive approach with a shorter recovery period and enhanced visualization. Its use extends to pediatric fractures and complex cases such as Maisonneuve and calcaneal fractures, potentially improving outcomes while minimizing complications. Understanding the evolving indications and benefits of arthroscopy for ankle fractures can lead to improved clinical outcomes and reduced complications.

The fundamental principles for treating ankle fractures, as with other intra-articular fractures, are anatomical reduction and stable internal fixation. Despite successful reduction, between 14% and 40% of patients continue to experience persistent pain or unsatisfactory functional outcomes. Furthermore, approximately 1% of patients progress to post-traumatic arthritis, necessitating further surgical intervention. Ankle fractures are frequently accompanied by intra-articular injuries, including osteochondral lesions, ligament tears, and syndesmosis injuries. Arthroscopy is becoming increasingly prevalent in managing acute ankle fractures by assessing intra-articular damage and facilitating accurate reduction. This review examined the role and indications for arthroscopy in ankle fractures, particularly emphasizing its benefits in diagnosing and managing associated injuries, including osteochondral lesions, syndesmosis, and deltoid ligament injuries. Furthermore, arthroscopy facilitates fracture reduction, offering a minimally invasive approach with a shorter recovery period and enhanced visualization. Its use extends to pediatric fractures and complex cases such as Maisonneuve and calcaneal fractures, potentially improving outcomes while minimizing complications. Understanding the evolving indications and benefits of arthroscopy for ankle fractures can lead to improved clinical outcomes and reduced complications.

The fundamental principles for treating ankle fractures, as with other intra-articular fractures, are anatomical reduction and stable internal fixation. Despite successful reduction, between 14% and 40% of patients continue to experience persistent pain or unsatisfactory functional outcomes. Furthermore, approximately 1% of patients progress to post-traumatic arthritis, necessitating further surgical intervention. Ankle fractures are frequently accompanied by intra-articular injuries, including osteochondral lesions, ligament tears, and syndesmosis injuries. Arthroscopy is becoming increasingly prevalent in managing acute ankle fractures by assessing intra-articular damage and facilitating accurate reduction. This review examined the role and indications for arthroscopy in ankle fractures, particularly emphasizing its benefits in diagnosing and managing associated injuries, including osteochondral lesions, syndesmosis, and deltoid ligament injuries. Furthermore, arthroscopy facilitates fracture reduction, offering a minimally invasive approach with a shorter recovery period and enhanced visualization. Its use extends to pediatric fractures and complex cases such as Maisonneuve and calcaneal fractures, potentially improving outcomes while minimizing complications. Understanding the evolving indications and benefits of arthroscopy for ankle fractures can lead to improved clinical outcomes and reduced complications.

Esophageal perforation can lead to serious complications, and rapid diagnosis and treatment significantly affect the prognosis. Endoscopic vacuum-assisted closure (EndoVAC) therapy is widely accepted as a safe, well-tolerated, effective, versatile and practical procedure for the management of esophageal perforation in selected patients. We report the successful use of EndoVAC therapy for management of an esophageal perforation secondary to foreign body removal. A 56-year-old man presented to the emergency department for evaluation of chest pain after swallowing the plastic shell of a pill. Emergency endoscopy revealed an esophageal wall laceration (approximately 3 cm) and microperforation. The esophageal laceration and microperforation were limited to the mid-esophagus. The patient underwent EndoVAC therapy, which was repeated every 3–4 days for a total of six sessions over a period of 21 days. We observed improvement in the esophageal injury with granulation tissue formation during the fifth session. Subsequent follow-up evaluation, including esophagography and chest computed tomography confirmed complete healing of the esophageal injury. Following resumption of diet, the patienton a was discharged without any complications.

Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOPinduced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

Background/Aims: Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of fexuprazan in patients with acute or chronic gastritis. Methods: In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events. Results: Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p<0.001, respectively). Likewise, both fexuprazan 20 mg q.d. and 10 mg b.i.d. also showed higher erosion healing rates than the placebo (p=0.033 and p=0.010, respectively). No difference was noted in the edema healing rate and the improvement rates for redness, hemorrhage, and subjective symptoms between the fexuprazan and placebo groups.No significant difference was noted in the incidence of adverse drug reactions. Conclusions Fexuprazan 20 mg q.d. and 10 mg b.i.d. for 2 weeks showed therapeutic efficacy superior to that of placebo in patients with acute or chronic gastritis (ClinicalTrials.gov identifier NCT04341454).

We used a heterozygous gene deletion library of fission yeasts comprising all essential and non-essential genes for a microarray screening of target genes of the antifungal terbinafine, which inhibits ergosterol synthesis via the erg1 enzyme. We identified 14 heterozygous strains corresponding to 10 non-essential [7 ribosomal-protein (RP) coding genes, spt7, spt20, and elp2] and 4 essential genes (tif302, rpl2501, rpl31, and erg1). Expectedly, their erg1 mRNA and protein levels had decreased compared to the control strain SP286. When we studied the action mechanism of the non-essential target genes using cognate haploid deletion strains, knockout of SAGA-subunit genes caused a down-regulation in erg1 transcription compared to the control strain ED668. However, knockout of RP genes conferred no susceptibility to ergosterol-targeting antifungals. Surprisingly, the RP genes participated in the erg1 transcription as components of repressor complexes as observed in a comparison analysis of the experimental ratio of erg1 mRNA. To understand the action mechanism of the interaction between the drug and the novel essential target genes, we performed isobologram assays with terbinafine and econazole (or cycloheximide). Terbinafine susceptibility of the tif302 heterozygous strain was attributed to both decreased erg1 mRNA levels and inhibition of translation. Moreover, Tif302 was required for efficacy of both terbinafine and cycloheximide. Based on a molecular modeling analysis, terbinafine could directly bind to Tif302 in yeasts, suggesting Tif302 as a potential off-target of terbinafine. In conclusion, this genome-wide screening system can be harnessed for the identification and characterization of target genes under any condition of interest.

Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)‒positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) ‘biological process’ terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including ‘cell cycle’ (cdc2, rik1, pas1, and leo1), ‘signaling’ (sck2, oga1, and cki3), and ‘vesicle-mediated transport’ (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the ‘signaling’ GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.

Econazole, a potent broad-spectrum antifungal agent and a Ca2+ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.