A lactate-induced response to hypoxia.

Organisms must be able to respond to low oxygen in a number of homeostatic and pathological contexts. Regulation of hypoxic responses via the hypoxia-inducible factor (HIF) is well established, but evidence indicates that other, HIF-independent mechanisms are also involved. Here, we report a hypoxic response that depends on the accumulation of lactate, a metabolite whose production increases in hypoxic conditions. We find that the NDRG3 protein is degraded in a PHD2/VHL-dependent manner in normoxia but is protected from destruction by binding to lactate that accumulates under hypoxia. The stabilized NDRG3 protein binds c-Raf to mediate hypoxia-induced activation of Raf-ERK pathway, promoting angiogenesis and cell growth. Inhibiting cellular lactate production abolishes the NDRG3-mediated hypoxia responses. Our study, therefore, elucidates the molecular basis for lactate-induced hypoxia signaling, which can be exploited for the development of therapies targeting hypoxia-induced diseases.

Exosomal miR-205-5p Improves Endometrial Receptivity by Upregulating E-Cadherin Expression through ZEB1 Inhibition.

Endometrial receptivity is a complex process that prepares the uterine endometrium for embryo implantation; insufficient endometrial receptivity is one of the causes of implantation failure. Here, we analyzed the microRNA expression profiles of exosomes derived from both receptive (RL95-2) and non-receptive (AN3-CA) endometrial epithelial cell (EEC) lines to identify exosomal miRNAs closely linked to endometrial receptivity. Among the 466 differentially expressed miRNAs, miR-205-5p was the most highly expressed in exosomes secreted from receptive RL95-2 cells. miR-205-5p, enriched at the adhesive junction, was closely related to endometrial receptivity. ZEB1, a transcriptional repressor of E-cadherin associated with endometrial receptivity, was identified as a direct target of miR-205-5p. miR-205-5p expression was significantly lower in the endometrial tissues of infertile women than in that of non-infertile women. In vivo, miR-205-5p expression was upregulated in the post-ovulatory phase, and its inhibitor reduced embryo implantation. Furthermore, administration of genetically modified exosomes overexpressing miR-205-5p mimics upregulated E-cadherin expression by targeting ZEB1 and improved spheroid attachment of non-receptive AN3-CA cells. These results suggest that the miR-205-5p/ZEB1/E-cadherin axis plays an important role in regulating endometrial receptivity. Thus, the use of exosomes harboring miR-205-5p mimics can be considered a potential therapeutic approach for improving embryo implantation.

Ceria-Zirconia nanoparticles reduce intracellular globotriaosylceramide accumulation and attenuate kidney injury by enhancing the autophagy flux in cellular and animal models of Fabry disease.

BACKGROUND: Fabry disease (FD) is a lysosome storage disease (LSD) characterized by significantly reduced intracellular autophagy function. This contributes to the progression of intracellular pathologic signaling and can lead to organ injury. Phospholipid-polyethyleneglycol-capped Ceria-Zirconia antioxidant nanoparticles (PEG-CZNPs) have been reported to enhance autophagy flux. We analyzed whether they suppress globotriaosylceramide (Gb3) accumulation by enhancing autophagy flux and thereby attenuate kidney injury in both cellular and animal models of FD. RESULTS: Gb3 was significantly increased in cultured human renal proximal tubular epithelial cells (HK-2) and human podocytes following the siRNA silencing of α galactosidase A (α-GLA). PEG-CZNPs effectively reduced the intracellular accumulation of Gb3 in both cell models of FD and improved both intracellular inflammation and apoptosis in the HK-2 cell model of FD. Moreover these particles attenuated pro fibrotic cytokines in the human podocyte model of FD. This effect was revealed through an improvement of the intracellular autophagy flux function and a reduction in reactive oxygen species (ROS). An FD animal model was generated in which 4-week-old male B6;129-Glatm1Kul/J mice were treated for 8 weeks with 10 mg/kg of PEG-CZNPs (twice weekly via intraperitoneal injection). Gb3 levels were reduced in the kidney tissues of these animals, and their podocyte characteristics and autophagy flux functions were preserved. CONCLUSIONS: PEG-CZNPs alleviate FD associated kidney injury by enhancing autophagy function and thus provide a foundation for the development of new drugs to treat of storage disease.

Reconstruction of Digit Soft Tissue Defects With the Fourth Common Digital Artery Perforator Flap.

PURPOSE: The hand has unique skin characteristics. Intrinsic flap donors are limited due to functional specificity and compactly connected structures. The hypothenar area is a reliable option for the reconstruction of finger defects. We performed anatomic studies elucidating the blood supply of this area and hypothesized that the fourth common palmar digital artery perforator free flap can be used to reconstruct soft tissue defects in fingers with minimal donor site morbidity. METHODS: From November 2017 to February 2020, 30 procedures of fourth common digital artery perforator free flaps were performed to cover digital skin defects. A retrospective chart review was performed, and the cases were analyzed. RESULTS: The mean patient age was 42.4 years (range, 1-75 years; median age, 40 years). Defects were located at the fingertip (n = 12), the dorsum (n = 3), the palmar (n = 9) aspect of the finger, and both the dorsal and palmar aspects of the finger (n = 6). Indications included emergent coverage (n = 13), coverage after necrosis (n = 11), oncological resection (n = 1), and contracture release (n = 5). The defect size ranged from 1.5 × 0.8 cm (1.2 cm2) to 6 × 2.5 cm (15 cm2). The perforator was located approximately 1 cm proximal to the distal palmar crease as it arose from the fourth common digital artery at a right angle. It continued to the ulnar border of the hand through the superficial fascia of the hypothenar muscles before running in a proximoulnar direction toward the dorsum of the hand. The diameter of the perforator was between 0.5 and 0.7 mm. All flaps survived. One case required a split-thickness skin graft for donor site closure, and all others could be closed primarily. CONCLUSIONS: The fourth common digital artery perforator is a versatile flap and can be used for both palmar and dorsal defects, including for the fingertip. The location of the perforator used differs from previous descriptions but is routinely and reliably located. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

The miR-182-5p/NDRG1 Axis Controls Endometrial Receptivity through the NF-κB/ZEB1/E-Cadherin Pathway.

Endometrial receptivity is essential for successful pregnancy, and its impairment is a major cause of embryo-implantation failure. MicroRNAs (miRNAs) that regulate epigenetic modifications have been associated with endometrial receptivity. However, the molecular mechanisms whereby miRNAs regulate endometrial receptivity remain unclear. Therefore, we investigated whether miR-182 and its potential targets influence trophoblast cell attachment. miR-182 was expressed at lower levels in the secretory phase than in the proliferative phase of endometrium tissues from fertile donors. However, miR-182 expression was upregulated during the secretory phase in infertile women. Transfecting a synthetic miR-182-5p mimic decreased spheroid attachment of human JAr choriocarcinoma cells and E-cadherin expression (which is important for endometrial receptivity). miR-182-5p also downregulated N-Myc downstream regulated 1 (NDRG1), which was studied further. NDRG1 was upregulated in the secretory phase of the endometrium tissues and induced E-cadherin expression through the nuclear factor-κΒ (NF-κΒ)/zinc finger E-box binding homeobox 1 (ZEB1) signaling pathway. NDRG1-overexpressing or -depleted cells showed altered attachment rates of JAr spheroids. Collectively, our findings indicate that miR-182-5p-mediated NDRG1 downregulation impaired embryo implantation by upregulating the NF-κΒ/ZEB1/E-cadherin pathway. Hence, miR-182-5p is a potential biomarker for negative selection in endometrial receptivity and a therapeutic target for successful embryo implantation.

Regulation of hypoxia responses by flavin adenine dinucleotide-dependent modulation of HIF-1α protein stability.

Oxygen deprivation induces a range of cellular adaptive responses that enable to drive cancer progression. Here, we report that lysine-specific demethylase 1 (LSD1) upregulates hypoxia responses by demethylating RACK1 protein, a component of hypoxia-inducible factor (HIF) ubiquitination machinery, and consequently suppressing the oxygen-independent degradation of HIF-1α. This ability of LSD1 is attenuated during prolonged hypoxia, with a decrease in the cellular level of flavin adenine dinucleotide (FAD), a metabolic cofactor of LSD1, causing HIF-1α downregulation in later stages of hypoxia. Exogenously provided FAD restores HIF-1α stability, indicating a rate-limiting role for FAD in LSD1-mediated HIF-1α regulation. Transcriptomic analyses of patient tissues show that the HIF-1 signature is highly correlated with the expression of LSD1 target genes as well as the enzymes of FAD biosynthetic pathway in triple-negative breast cancers, reflecting the significance of FAD-dependent LSD1 activity in cancer progression. Together, our findings provide a new insight into HIF-mediated hypoxia response regulation by coupling the FAD dependence of LSD1 activity to the regulation of HIF-1α stability.

Homeobox A9 directly targeted by miR-196b regulates aggressiveness through nuclear Factor-kappa B activity in non-small cell lung cancer cells.

MicroRNAs (miRNAs) are recognized as crucial posttranscriptional regulators of gene expression, and play critical roles as oncogenes or tumor suppressors in various cancers. Here, we show that miR-196b is upregulated in mesenchymal-like-state non-small cell lung cancer (NSCLC) cells and lung cancer tissues. Moreover, miR-196b upregulation stimulates cell invasion and a change in cell morphology to a spindle shape via loss of cell-to-cell contacts. We identified homeobox A9 (HOXA9) as a target gene of miR-196b by using public databases such as TargetScan, miRDB, and microRNA.org. HOXA9 expression is inversely correlated with miR-196b levels in clinical NSCLC samples as compared to that in corresponding control samples, and with the migration and invasion of NSCLC cells. Ectopic expression of HOXA9 resulted in a suppression of miR-196b-induced cell invasion, and HOXA9 reexpression increased E-cadherin expression. Furthermore, HOXA9 potently attenuated the expression of snail family zinc finger 2 (SNAI2/SLUG) and matrix metallopeptidase 9 (MMP9) by controlling the binding of nuclear factor-kappa B to the promoter of SLUG and MMP9 genes, respectively. Therefore, we suggest that HOXA9 plays a central role in controlling the aggressive behavior of lung cancer cells and that miR-196b can serve as a potential target for developing anticancer agents. © 2015 Wiley Periodicals, Inc.

Lateral Nail Fold Incision Technique for Venous Anastomosis in Fingertip Replantation.

BACKGROUND: Successful venous anastomosis is one of the most important factors in fingertip replantation. Volar veins in the fingertip course proximally in a random pattern, which makes it difficult to find out the exact locations. Although dorsal veins in the lateral nail fold have constant location and adequate diameter for anastomosis, they have been known as hard to dissect from the immobile subcutaneous tissue. The authors present a new lateral nail fold incision technique for venous anastomosis in the fingertip amputations. METHODS: From February 2010 to October 2010, 9 replantations using the new incision and venous anastomosis technique were performed in 9 patients. The levels of amputations were from the nail base to half of the nail bed. After repairing the proper digital arteries, a skin incision was made along the junction between the lateral nail fold and nail bed. Careful dissection was performed to isolate the veins in the lateral nail fold. After evaluation of the suitability of the vessel, venous anastomosis was performed. RESULTS: Seven male and 2 female patients were enrolled in this study. Appropriate dorsal veins for anastomosis could be found in 8 of 9 patients. All the replanted stumps survived without venous congestion and following additional procedures. A sizable volar or dorsal vein could not be found in 1 patient. The salvage technique was required in this patient. CONCLUSIONS: Dorsal veins in the lateral nail fold can be found easily because of the constant anatomical location. The new incision on the lateral nail fold provides not only sufficient operative field for anastomosis but also additional opportunity of successful venous anastomosis in the selected cases. The authors, therefore, propose this technique as an effective method for an alternative venous anastomosis in the zone I replantation.

SH3RF2 functions as an oncogene by mediating PAK4 protein stability.

SH3RF (SH3-domain-containing RING finger protein) family members, SH3RF1-3, are multidomain scaffold proteins involved in promoting cell survival and apoptosis. In this report, we show that SH3RF2 is an oncogene product that is overexpressed in human cancers and regulates p21-activated kinase 4 (PAK4) protein stability. Immunohistochemical analysis of 159 colon cancer tissues showed that SH3RF2 expression levels are frequently elevated in cancer tissues and significantly correlate with poor prognostic indicators, including increased invasion, early recurrence and poor survival rates. We also demonstrated that PAK4 protein is degraded by the ubiquitin-proteasome system and that SH3RF2 inhibits PAK4 ubiquitination via physical interaction-mediated steric hindrance, which results in the upregulation of PAK4 protein. Moreover, ablation of SH3RF2 expression attenuates TRADD (TNFR-associated death domain) recruitment to tumor necrosis factor-α (TNF-α) receptor 1 and hinders downstream signals, thereby inhibiting NF-κB (nuclear factor-kappaB) activity and enhancing caspase-8 activity, in the context of TNF-α treatment. Notably, ectopic expression of SH3RF2 effectively prevents apoptosis in cancer cells and enhances cell migration, colony formation and tumor growth in vivo. Taken together, our results suggest that SH3RF2 is an oncogene that may be a definitive regulator of PAK4. Therefore, SH3RF2 may represent an effective therapeutic target for cancer treatment.

Knockdown of anterior gradient 2 expression extenuates tumor-associated phenotypes of SNU-478 ampulla of Vater cancer cells.

BACKGROUND: Anterior gradient 2 (AGR2) has been implicated in tumor-associated phenotypes such as cell viability, invasion and metastasis in various human cancers. However, the tumor promoting activity of AGR2 has not yet been determined in biliary tract cancers. Thus, we examined the expression of AGR2 and its tumor-promoting activity in biliary tract cancer cells in this study. METHODS: Expression of AGR2 mRNA and protein was analyzed by real time RT-PCR and western blotting, respectively. MTT assay was employed to measure cell viability and pulsed BrdU incorporation by proliferating cells was monitored by flow cytometry. Soft agar colony formation assay and transwell invasion assay were employed to determine anchorage-independent growth and in vitro invasion of the tumor cells, respectively. In vivo tumor formation was examined by injection of tumor cells into immunocompromised mice subcutaneously. Statistical analysis was performed with 2-tailed unpaired Student's t-test for continuous data and with one-way ANOVA for multiple group comparisons. Bonferroni tests were used for post hoc 2-sample comparisons. RESULTS: AGR2 mRNA was detected in SNU-245, SNU-478, and SNU-1196 cell lines, and its protein expression was confirmed in SNU-478 and SNU-245 cell lines by western blot analysis. Knockdown of AGR2 expression with an AGR2-specific short hairpin RNA (shRNA) in SNU-478, an ampulla of Vater cancer cell line resulted in decreased cell viability and in decreased anchorage-independent growth by 98%. The AGR2 knockdown also increased the sensitivity of the cells to chemotherapeutic drugs, including gemcitabine, 5-fluorouracil and cisplatin. In addition, SNU-478 cells expressing AGR2-shRNA failed to form detectable tumor xenografts in nude mice, whereas control cells formed tumors with an average size of 179 ± 84 mm3 in 3 weeks. Overexpression of AGR2 in SNU-869 cells significantly increased cell viability through enhanced cell proliferation and the number of Matrigel™-invading cells compared with AGR2-negative SNU-869 cells. CONCLUSIONS: Our findings implicate that AGR2 expression augments tumor-associated phenotypes by increasing proliferative and invasive capacities of the ampulla of Vater cancer cells.

Serious Complications of the Percutaneous A1 Pulley Release: Case Reports and Literature Review.

Percutaneous first annular pulley (A1 pulley) release, which has been increasingly used to treat trigger fingers, has been widely established as a safe and simple procedure. Multiple studies have reported positive results of percutaneous A1 pulley release. In this study, however, we report cases of patients who developed complications after undergoing percutaneous A1 pulley release at local clinics. A total of six patients visited our hospital for infectious complications after percutaneous A1 pulley release. Various sequelae such as damage to normal structures, insufficient procedure, and tissue necrosis were observed during the exploration. A retrospective study was conducted to identify the cause and trend of the observed complications by instruments (HAKI knife or needle). In the HAKI knife group, there was a tendency for damage to normal structures, while in the needle group, an insufficient release or serious soft tissue necrosis was observed. Based on these cases, our findings confirm the existence and characteristics of infectious complications following the percutaneous A1 pulley release. We further identify that the type of instrument used predicts the nature of complications. Thus, reliable and skilled performance of the procedure by experts is essential for safe treatment.

Distal fingertip replantation: indications, strategy and postoperative management.

Distal fingertip replantation is associated with being a technically demanding procedure and dubious outcomes, although it is now performed more frequently across the world. However, the technique and outcomes remain controversial with disagreement among replantation surgeons due to lack of consensus about the indications, intraoperative strategy and postoperative regimes. In this article, we asked six experienced hand surgeons several pertinent questions that every replantation surgeon performing distal fingertip replantation would face in their clinical practice. The article summarizes their responses, which might provide valuable insight to every replantation surgeon in different parts of their career while managing these injuries.

Hand Reconstruction Using Anterolateral Thigh Free Flap by Terminal Perforator-to-Digital Artery Anastomosis: Retrospective Analysis.

This study aimed to analyze cases of anterolateral thigh (ALT) free flap used for hand reconstruction with terminal perforator-to-digital artery anastomosis. Patients who underwent ALT free flap placement with terminal perforator-to-digital artery anastomosis for hand reconstruction between January 2011 and August 2021 were included. The number, length, and diameter of the perforators and veins, flap size, and operative time were investigated through a retrospective review of charts and photographs. The occurrences of arterial thrombosis, venous thrombosis, arterial spasm, and flap necrosis were analyzed. In total, 50 patients were included in this study. The mean diameter and length of the perforators were 0.68 mm and 3.25 cm, respectively, and the mean number of veins anastomosed was 1.88, with a mean diameter of 0.54 mm. Complications included four cases of arterial thrombosis, one case of venous thrombosis, seven cases of partial necrosis, and one case of total flap failure. Regression analysis showed that a longer perforator was associated with arterial thrombosis whereas larger flap size and number of anastomosed veins were associated with partial necrosis ( p < 0.05). The terminal perforator-to-digital artery anastomosis offers advantages in using compact free flaps with short pedicle lengths to cover small hand defects.

The "Swing-Door" Regrafting of Donor Site: An Alternative Method for Split-Thickness Skin Graft in the Hand.

Background Skin defects in the hands are common injuries, and autologous skin grafting is the ideal treatment. However, complications can occur at the donor and recipient sites. This study compares the "Swing-door" technique with conventional skin grafting. Methods From August 2019 to February 2023, 19 patients with skin defects of hand underwent the "Swing-door" split-thickness skin graft (STSG) technique. The thin epithelial layer was elevated with proximal part attached. Skin graft was harvested beneath. Donor site was then closed with epithelial flap like a "Swing-door". The outcomes were evaluated in terms of healing time, scar formation, and pain at the donor and recipient sites. The data were compared with the conventional STSG. Results The "Swing-door" group had lower graft take percentages, but complications did not significantly differ between the two groups. The "Swing-door" technique resulted in better cosmetic outcomes, as evidenced by lower Vancouver Scar Scale scores, faster donor site epithelialization, and reduced pain and discomfort during the early postoperative period, as measured by Visual Analog Scale. Conclusion The "Swing-door" STSG is a useful alternative for treating hand skin defects.

Exosomal miR-196b secreted from bronchial epithelial cells chronically exposed to low-dose PM2.5 promotes invasiveness of adjacent and lung cancer cells.

Fine particulate matter (PM2.5) is a risk factor for pulmonary diseases and lung cancer, and inhaled PM2.5 is mainly deposited in the bronchial epithelium. In this study, we investigated the effect of long-term exposure to low-dose PM2.5 on BEAS-2B cells derived from the normal bronchial epithelium. BEAS-2B cells chronically exposed to a concentration of 5µg/ml PM2.5 for 30 passages displayed the phenotype promoting epithelial-mesenchymal transition (EMT) and cell invasion. Cellular internalization of exosomes (designated PM2.5 Exo) extracted from BEAS-2B cells chronically exposed to low-dose PM2.5 promoted cell invasion in vitro and metastatic potential in vivo. Hence, to identify the key players driving phenotypic alterations, we analyzed microRNA (miRNA) expression profiles in PM2.5 Exo. Five miRNAs with altered expression were selected: miRNA-196b-5p, miR-135a-2-5p, miR-3117-3p, miR-218-5p, and miR-497-5p. miR-196b-5p was the most upregulated in both BEAS-2B cells and isolated exosomes after PM2.5 exposure. In a functional validation study, genetically modified exosomes overexpressing a miR-196b-5p mimic induced an enhanced invasive phenotype in BEAS-2B cells. Conversely, miR-196b-5p inhibition diminished the PM2.5-enhanced EMT and cell invasion. These findings indicate that exosomal miR-196b-5p may be a candidate biomarker for predicting the malignant behavior of the bronchial epithelium and a therapeutic target for inhibiting PM2.5-triggered pathogenesis.

Unintentional Injection Into the Retrodural Space of Okada During Transforaminal Epidural Steroid Injection.

BACKGROUND: Transforaminal epidural steroid injection (TFESI) is commonly used for radicular pain, but can lead to an unintentional injection into the retrodural Space of Okada (RSO), an extradural space located dorsal to the ligamentum flavum, instead of the epidural space. OBJECTIVES: To determine the prevalence and describe the fluoroscopic imaging features of an unintentional injection into the RSO during a TFESI and to review the history of injections into the RSO. STUDY DESIGN: Observational study and original research. SETTING: This work was conducted at Jeju National University School of Medicine, Jeju, Republic of Korea. METHODS: A total of 5,429 lumbar TFESIs performed from the September 1, 2018 through October 31, 2021 were analyzed for unintentional RSO injections using fluoroscopic-guided contrast medium patterns. RESULTS: The rate of unintentional injection into the RSO was 0.20% (11 incidents). Contrast medium patterns in the RSO had a sigmoid or ovoid shape confined to the affected facet joint, or a butterfly-shaped pattern extending into the contralateral facet joint, but rarely extending beyond the upper or lower level. LIMITATION: The rarity of unintentional injection into the RSO prevented a randomized controlled study design. CONCLUSIONS: Careful fluoroscopic examination of contrast medium patterns during lumbar TFESI is crucial to identify needle placement in the RSO. If detected, the procedure can be corrected by slightly advancing the needle into the foramen.

High positive end-expiratory pressure preserves cerebral oxygen saturation during laparoscopic cholecystectomy under propofol anesthesia.

BACKGROUND: Positive end-expiratory pressure (PEEP) can improve respiratory mechanics during pneumoperitoneum, but may influence intracranial and cerebral perfusion pressure. This study investigated the changes in hemodynamic parameters and cerebral oxygen saturation (rSO(2)) associated with 10 cmH(2)O PEEP during pneumoperitoneum while undergoing laparoscopic cholecystectomy under propofol anesthesia. METHODS: Sixty patients aged 18-60 years undergoing laparoscopic cholecystectomy were randomly allocated into two groups: application of no external PEEP (ZEEP group, n = 30) or PEEP = 10 cmH(2)O (PEEP group, n = 30). PEEP was applied after insufflation of CO(2). Except for the PEEP level, all other ventilator settings were identical for both groups. Hemodynamic variables, end-tidal carbon dioxide concentration (ETCO(2)), ventilatory parameters, and rSO(2) were measured. RESULTS: There was no significant difference in rSO(2), mean arterial pressure (MAP), heart rate (HR), and ETCO(2) between the groups throughout the study. When compared with baseline, MAP, HR, and ETCO(2) increased significantly after insufflation of CO(2) in both groups, whereas rSO(2) did not change. No patient had cerebral desaturation, defined as rSO(2) <80 % of baseline or <50 % in both groups throughout the study. CONCLUSION: Application of PEEP with 10 cmH(2)O during CO(2) pneumoperitoneum could preserve the rSO(2) value and hemodynamic stability in patients undergoing laparoscopic cholecystectomy under propofol anesthesia.

Single or double Kirschner wire fixation: which provides better outcomes for pediatric proximal phalanx base fractures?

PURPOSE: The most common hand fracture in children is seen at the base of the proximal phalanx. This study aims to compare clinical outcomes of single versus double Kirschner wire pinning for pediatric proximal phalanx base fractures. PATIENTS AND METHODS: The retrospective study enrolled patients who underwent closed K-wire pinning for proximal phalanx base fractures from January 2016 to February 2022. We divided patients into two groups based on the number of K-wire inserted (single versus double). Demographics, removal of implant, complication rate were analyzed. Patients were asked to answer the Michigan Hand Outcomes Questionnaire (MHQ) by telephone. Data including fracture type, diaphyseal axis-metacarpal head angle (DHA) and Total Active Flexion Scale (TAFS) were analyzed. RESULTS: This study included 37 pediatric patients with proximal phalanx base fractures, treated with either single (n = 10) or double K-wire (n = 27) fixation. The mean operation time was significantly shorter for the single K-wire group. No significant differences were observed in complication rates, TAFS, implant removal times, MHQ, or pre- and post-operative DHA between the two groups. CONCLUSION: The single K-wire technique demonstrates similar effectiveness to the double K-wire technique in treating pediatric proximal phalanx base fractures, with the added benefit of shorter operation time. Therefore, the choice between using one or two K-wires should be determined based on the surgeon's proficiency and preference.

Regulating POLR3G by MicroRNA-26a-5p as a promising therapeutic target of lung cancer stemness and chemosensitivity.

Cancer stem cells (CSCs) identified in lung cancer exhibit resistance to chemotherapy, radiotherapy, and targeted therapy. Therefore, a technology for controlling CSCs is needed to overcome such resistance to cancer therapy. Various evidences about the association between epithelial-mesenchymal transition related transcriptomic alteration and acquisition of CSC phenotype have been proposed recently. Down-regulated miR-26a-5p is closely related to mesenchymal-like lung cancer cell lines. These findings suggest that miR-26a-5p might be involved in lung cancer stemness. RNA polymerase III subunit G (POLR3G) was selected as a candidate target of miR-26a-5p related to cancer stemness. It was found that miR-26a-5p directly regulates the expression of POLR3G.Overexpression of miR-26a-5p induced a marked reduction of colony formation and sphere formation. Co-treatment of miR-26a-5p and paclitaxel decreased cell growth, suggesting that miR-26a-5p might play a role as a chemotherapy sensitizer. In the cancer genome atlas data, high miR-26a-5p and low POLR3G expression were also related to higher survival rate of patients with lung adenocarcinoma. These results suggest that miR-26a-5p can suppress lung cancer stemness and make cancer cell become sensitive to chemotherapy. This finding provides a novel insight into a potential lung cancer treatment by regulating stemness.

Smart syringe using actuator and force sensor for epidural anesthesia injection.

The anesthesia process in the epidural space is quite difficult as it requires a high level of skill. Therefore, a medical accident occurs, and intensive training is required. In order to reduce these medical accidents, medical technology is being developed, which provides safe and accurate treatment services. This paper proposes a smart syringe design for safe and accurate anesthesia in the epidural space. The smart syringe is designed to measure the electrical sensing waveform by using a sensor instead of the sense of the hand during anesthesia and show the position of the needle through external monitoring. To design a smart syringe, a force sensor, actuator, and CPU were used, and a 3D printer was used to produce the outer shape. An animal test was conducted to evaluate the performance test of the smart syringe, and satisfactory results were obtained by measuring the needle insertion process of the smart syringe and the position of the needle through the animal experiment.