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.

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.

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.

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.

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.

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.

R-PTP-κ Inhibits Contact-Dependent Cell Growth by Suppressing E2F Activity.

Density-dependent regulation of cell growth is presumed to be caused by cell-cell contact, but the underlying molecular mechanism is not yet clearly defined. Here, we report that receptor-type protein tyrosine phosphatase-kappa (R-PTP-κ) is an important regulator of cell contact-dependent growth inhibition. R-PTP-κ expression increased in proportion to cell density. siRNA-mediated R-PTP-κ downregulation led to the loss of cell contact-mediated growth inhibition, whereas its upregulation reduced anchorage-independent cell growth in soft agar as well as tumor growth in nude mice. Expression profiling and luciferase reporter system-mediated signaling pathway analysis revealed that R-PTP-κ induced under cell contact conditions distinctly suppressed E2F activity. Among the structural domains of R-PTP-κ, the cytoplasmic domain containing the tandemly repeated PTP motif acts as a potent downregulator of the E2F pathway. Specifically, R-PTP-κ suppressed CDK2 activity through the induction of p21Cip1/WAF-1 and p27Kip1, resulting in cell cycle arrest at the G1 phase. In transcriptome-based public datasets generated from four different tumor types, R-PTP-κ expression was negatively correlated with the expression pattern and prognostic value of two known E2F1 target genes (CCNE1 and CDC25A). Therefore, our results indicate that the R-PTP-κ-E2F axis plays a crucial role in cell growth-inhibitory signaling arising from cell-cell contact conditions.

A Comparison of Anesthetic Quality between Single and Septum-based Double Injection for Ultrasound-Guided Costoclavicular Block: A Randomized Controlled Trial.

BACKGROUND: In a costoclavicular (CC) approach of an ultrasound (US)-guided infraclavicular brachial plexus block (BPB), a septum between the lateral and the medial/posterior cords can result in an incomplete block. We hypothesized that double injections in each compartment between the septum would result in a higher success rate of BPB than a single injection in the center of the CC space. OBJECTIVES: This study was conducted to confirm the superiority of block quality achieved by septum-based double injections (experimental group; group E) over single injection in the center of the CC space (control group; group C). STUDY DESIGN: A randomized, controlled trialSETTING: Department of Anesthesiology and Pain Medicine, Korea University College of Medicine, Anam Hospital. METHODS: Sixty-eight patients who underwent upper extremity surgery randomly received a single (SI group, n = 34) or a septum-based double injection (DI group, n = 34) using the CC approach. Ten milliliters of 2% lidocaine, 10 mL of 0.75% ropivacaine, and 5 mL of normal saline were used for BPB in each group (total 25 mL). Sensory-motor blockade of the ipsilateral median, radial, ulnar, and musculocutaneous nerves was assessed by a blinded observer at 5-minute intervals for 30 minutes immediately after local anesthesia administration. The assessed variables were the success rate, the rate of all 4 nerves blockade, and onset time. RESULTS: Thirty minutes after the block, the success rate was significantly higher in the DI group than in the SI group (64.7% in the SI group vs 91.2% in the DI group, P = 0.009), and the rate of all 4 nerves blockade also significantly increased in the DI group compared to the SI group (44.1% in the SI group vs 91.2% in the DI group, P = 0). The onset time was significantly shortened in the DI group compared with the SI group (26.3 ± 5.6 min in the SI group vs 21.3 ± 6.2 min in the DI group, P = 0.010). LIMITATIONS: We considered that the location of the septum was always between the lateral cord superficially and the medial/posterior cords below it. In some patients in whom the septum was not visible, a superficial lateral cord was injected first, and then deep medial and posterior cords were injected, assuming that the 2 compartments were divided by the septum. CONCLUSIONS: Compared with the SI, the septum-based DI of CC approach increased the success rate and the rate of all 4 nerves blockade and shortened the onset time.

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.

Glycogen Storage Disease Phenotypes Accompanying the Perturbation of the Methionine Cycle in NDRG3-Deficient Mouse Livers.

N-Myc downstream regulated gene 3 (NDRG3) is a unique pro-tumorigenic member among NDRG family genes, mediating growth signals. Here, we investigated the pathophysiological roles of NDRG3 in relation to cell metabolism by disrupting its functions in liver. Mice with liver-specific KO of NDRG3 (Ndrg3 LKO) exhibited glycogen storage disease (GSD) phenotypes including excessive hepatic glycogen accumulation, hypoglycemia, elevated liver triglyceride content, and several signs of liver injury. They suffered from impaired hepatic glucose homeostasis, due to the suppression of fasting-associated glycogenolysis and gluconeogenesis. Consistently, the expression of glycogen phosphorylase (PYGL) and glucose-6-phosphate transporter (G6PT) was significantly down-regulated in an Ndrg3 LKO-dependent manner. Transcriptomic and metabolomic analyses revealed that NDRG3 depletion significantly perturbed the methionine cycle, redirecting its flux towards branch pathways to upregulate several metabolites known to have hepatoprotective functions. Mechanistically, Ndrg3 LKO-dependent downregulation of glycine N-methyltransferase in the methionine cycle and the resultant elevation of the S-adenosylmethionine level appears to play a critical role in the restructuring of the methionine metabolism, eventually leading to the manifestation of GSD phenotypes in Ndrg3 LKO mice. Our results indicate that NDRG3 is required for the homeostasis of liver cell metabolism upstream of the glucose-glycogen flux and methionine cycle and suggest therapeutic values for regulating NDRG3 in disorders with malfunctions in these pathways.

LPIN1 Induces Gefitinib Resistance in EGFR Inhibitor-Resistant Non-Small Cell Lung Cancer Cells.

Drug resistance limits the efficacy of targeted therapies, including tyrosine kinase inhibitors (TKIs); however, a substantial portion of the drug resistance mechanisms remains unexplained. In this study, we identified LPIN1 as a key factor that regulates gefitinib resistance in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) cells. Unlike TKI-sensitive HCC827 cells, gefitinib treatment induced LPIN1 expression and increased diacylglycerol concentration in TKI-resistant H1650 cells, followed by the activation of protein kinase C delta and nuclear factor kappa B (NF-κB) in an LPIN1-dependent manner, resulting in cancer cell survival. Additionally, LPIN1 increased the production of lipid droplets, which play an important role in TKI drug resistance. All results were recapitulated in a patient-derived EGFR-mutant NSCLC cell line. In in vivo tumorigenesis assay, we identified that both shRNA-mediated depletion and pharmaceutical inhibition of LPIN1 clearly reduced tumor growth and confirmed that gefitinib treatment induced LPIN1 expression and LPIN1-dependent NF-κB activation (an increase in p-IκBα level) in tumor tissues. These results suggest an effective strategy of co-treating TKIs and LPIN1 inhibitors to prevent TKI resistance in NSCLC patients.

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.

Division of a single free flap in multiple digit reconstruction.

BACKGROUND: Single free flaps are a commonly used reconstructive method for multiple soft tissue defects in digits. We analyzed the flap size, division timing, and degree of necrosis in cases with various types of flap division. METHODS: We conducted a retrospective review of the medical charts of patients who had undergone single free flap reconstruction for multiple soft tissue defects across their digits from 2011 to 2020. The flap types included were the lateral arm free flap, venous forearm free flap, thenar free flap, hypothenar free flap, anterolateral thigh free flap, medial plantar free flap, and second toe pulp free flap. Flap size, anastomosed vessels, division timing, and occurrence of flap necrosis were retrospectively investigated and then analyzed using the t-test. RESULTS: In total, 75 patients were included in the analysis. The success rate of the free flaps was 97.3%. All flaps were successfully divided after at least 17 days, with a mean of 47.17 days (range, 17-243 days) for large flaps and 42.81 days (range, 20-130 days) for the medium and small flaps (P=0.596). The mean area of flap necrosis was 2.38% in the large flaps and 2.58% in the medium and small flaps (P=0.935). Severe necrosis of the divided flap developed in two patients who had undergone flap division at week 6 and week 34. CONCLUSIONS: In cases where blood flow to the flap has been stable for more than 3 weeks, flap division can be safely attempted regardless of the flap size.

Fingertip reconstruction with a subcutaneous flap and composite graft composed of nail bed and volar pulp skin.

BACKGROUND: Fingertip injuries are very common; however, the reconstruction of volar pulp defects with nail bed defects is challenging in the absence of the amputated segment. We reconstructed fingertip amputations with nail bed defects using a new surgical approach: a subcutaneous flap and composite graft. METHODS: We treated 10 fingertip amputation patients without an amputated segment, with exposed distal phalangeal bone and full-thickness nail bed defects between February 2018 and December 2020. All patients underwent two-stage surgery: in the first stage, a subcutaneous flap was performed to cover the exposed distal phalanx, and in the second stage, a composite graft, consisting of nail bed, hyponychium, and volar pulp skin, was applied over the subcutaneous flap. RESULTS: All flaps survived and all composite grafts were successful. The wounds healed without any significant complications, including the donor site. The average follow-up duration was 11.2 months (range, 3-27 months). The new nail and the shape of the volar pulp were evaluated during follow-up. All patients were satisfied with their natural fingertip shapes and the new nails did not have any serious deformities. CONCLUSIONS: A subcutaneous flap in combination with a composite graft fitting the shape of the defect could be another option for fingertip injuries without amputated segments.

Management of a mutilated hand: the current trends.

Mutilated upper limbs suffer loss of substance of various tissues with loss of prehension. The most important factor in salvage of a mutilated hand is involvement of a senior surgeon at the time of initial assessment and debridement. A regional block given on arrival helps through assessment and investigations in a pain-free state. Infection still remains the important negative determinant to outcome and is prevented by emergent radical debridement and early soft tissue cover. Radical debridement and secure skeletal stabilization must be achieved on day one in all situations. Dermal substitutes and negative pressure wound therapy are increasingly used but have not substituted regular soft tissue cover techniques. Ability to perform secondary procedures and the increased use of the reconstructed hand with time keeps reconstruction a better option than prosthesis fitting. Toe transfers and free functioning muscle transfers are the two major secondary procedures that have influenced outcomes.

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.

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.

PKM2 Regulates HSP90-Mediated Stability of the IGF-1R Precursor Protein and Promotes Cancer Cell Survival during Hypoxia.

Insulin-like growth factor-1 receptor (IGF-1R), an important factor in promoting cancer cell growth and survival, is commonly upregulated in cancer cells. However, amplification of the IGF1R gene is extremely rare in tumors. Here, we have provided insights into the mechanisms underlying the regulation of IGF-1R protein expression. We found that PKM2 serves as a non-metabolic protein that binds to and increases IGF-1R protein expression by promoting the interaction between IGF-1R and heat-shock protein 90 (HSP90). PKM2 depletion decreases HSP90 binding to IGF-1R precursor, thereby reducing IGF-1R precursor stability and the basal level of mature IGF-1R. Consequently, PKM2 knockdown inhibits the activation of AKT, the key downstream effector of IGF-1R signaling, and increases apoptotic cancer cell death during hypoxia. Notably, we clinically verified the PKM2-regulated expression of IGF-1R through immunohistochemical staining in a tissue microarray of 112 lung cancer patients, demonstrating a significant positive correlation (r = 0.5208, p < 0.0001) between PKM2 and IGF-1R expression. Together, the results of a previous report demonstrated that AKT mediates PKM2 phosphorylation at serine-202; these results suggest that IGF-1R signaling and PKM2 mutually regulate each other to facilitate cell growth and survival, particularly under hypoxic conditions, in solid tumors with dysregulated IGF-1R expression.