Spliceosome component TCERG1 regulates the aggressiveness of somatotroph adenoma.

PURPOSE: We aimed to identify differentially expressed spliceosome components in growth hormone (GH)-secreting pituitary tumors and investigate their roles in pathogenesis. METHODS: We performed transcriptome analysis of 20 somatotroph adenomas and 6 normal pituitary tissues to select dysregulated spliceosome components. Clinical characteristics were analyzed based on gene expression in 64 patients with acromegaly. Proliferation, invasion, and hormonal activity of GH secreting pituitary adenoma cells were investigated. RESULTS: TCERG1 expression was significantly higher in somatotroph adenomas than in normal pituitaries (log2 fold change 0.59, adjusted P = 0.0002*). Genotype-phenotype analysis revealed that patients with higher TCERG1 expression had lower surgical remission rates than those with lower expression (63.64% vs. 95.45%, P = 0.009*). TCERG1 expression was significantly higher in groups with cavernous sinus (CS) invasion or Ki67 index over 3 (all P>0.05*). TCERG1 overexpression led to a 29.60% increase in proliferation (P<0.001*) and a 249.47% increase in invasion after 48 h in GH3 cells (P = 0.026*). Conversely, TCERG1 silencing significantly decreased cell proliferation (25.76% at 72 h, P<0.001*) and invasion (96.87% at 48 h, P = 0.029*). E-cadherin was decreased, but vimentin was increased in both TCERG1 overexpressed GH3 cells and somatotroph adenomas. And TCERG1 silence reversed the expression of the genes (CDH2, SNAI1, ZEB2, and VIM) in GH3 cells. CONCLUSIONS: Spliceosome machinery provide novel insights into the pathogenesis of GH-secreting pituitary tumor and highlight the potential role of TCERG1 as a biomarker for tumor aggressiveness.

Excess endocrine growth hormone in acromegaly promotes the aggressiveness and metastasis of triple-negative breast cancer.

Pituitary adenoma-induced excess endocrine growth hormone (GH) secretion can lead to breast cancer development and metastasis. Herein, we used an acromegaly mouse model to investigate the role of excess endocrine GH on triple-negative breast cancer (TNBC) growth and metastasis. Additionally, we aimed to elucidate the molecular mechanism of transcription factor 20 (TCF20)/nuclear factor erythroid 2-related factor 2 (NRF2) signaling-mediated aggressiveness and metastasis of TNBC. Excess endocrine GH induced TCF20 activates the transcription of NRF2 and NRF2-target genes to facilitate TNBC metastasis. Inhibition of GH receptor (GHR) and TCF20 activity using the GHR antagonist or small-interfering RNA-induced gene knockdown resulted in reduced tumor volume and metastasis, suggesting that excess endocrine GH stimulates TCF20/NRF2 pathways in TNBC and promotes metastasis to the lung. GHR inhibitors present an effective therapeutic strategy to prevent TNBC cell growth and metastasis. Our findings revealed functional and mechanistic roles of the GH-TCF20-NRF2 signaling axis in TBNC progression.

Novel Lipid Nanocomplex Co-Carrying Bcl2 siRNA and Quantum Dots for EGF Receptor-Targeted Anti-Cancer Theranosis.

Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood-immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the lipid micellar structure capturing quantum dot (QD) for cancer theranosis. The QD/lipid micelles (QDMs) were prepared using a simple self-assembly procedure and then conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for tumor targeting. As a therapeutic agent, Bcl2 siRNA-cholesterol conjugates were loaded on the surface of QDMs. The EGFR-directed QDMs containing Bcl2 siRNA, so-called immuno-QDM/siBcl2 (iQDM/siBcl2), exhibited the more effective delivery of QDs and siBcl2 to target human colorectal cancer cells in cultures as well as in mouse xenografts. The effective in vivo targeting of iQDM/siBcl2 resulted in a more enhanced therapeutic efficacy of siBcl2 to the target cancer in mice. Based on the results, anti-EGFR QDM capturing therapeutic siRNA could be suggested as an alternative modality for tumor-targeted theranosis.

Inhibition of acid rock drainage with iron-silicate or phosphate film: in rainy and submerged environments.

Iron phosphate-based coating and iron silicate-based coating were used to inhibit the oxidation of sulfide minerals in rainy and submerged environments. The inhibiting effectiveness of coating agents on the oxidation of iron sulfide minerals was investigated using pyrite and rock samples resulting from acid drainage. The film formed with both surface-coating agents was identified by pyrite surface analysis. It was also confirmed that the formation of coatings varies depending on the crystallographic orientation. The inhibitory effects under rainy and submerged conditions were investigated using column experiments. Submerged conditions accelerated deterioration compared to that under rainy conditions. Iron phosphate coating had a significantly better oxidation-inhibitory effect (84.86-98.70%) than iron silicate coating (56.80-92.36%), and at a concentration of 300 mM, H+ elution was inhibited by more than 90% throughout the experiment. Furthermore, methods for effective film formation were investigated in terms of producing Fe3+; (1) application of coating agents mixed with oxidant (H2O2), (2) application of coating agent after the use of the oxidant. In a rainy environment, applying iron phosphate-based coating using the sequential method showed oxidation inhibition effects for cycles 1-9, whereas applying the mixed material showed effects for cycles 9-13. The use of a surface-coating agent after applying an oxidant did not inhibit oxidation. The surface coating agent and the oxidizing agent should be applied as a mixture to form a film.

Fabrication of atelocollagen-coated bioabsorbable suture and the evaluation of its regenerative efficacy in Achilles tendon healing using a rat experimental model.

Recently, the incidence of Achilles tendon ruptures (ATRs) has become more common, and repair surgery using a bioabsorbable suture is generally preferred, particularly in the case of healthy patients. Sutures composed of poly(lactic-co-glycolic acid) (PLGA) are commonly used in ATR surgeries. Nevertheless, owing to the inherent limitations of PLGA, novel bioabsorbable sutures that can accelerate Achilles tendon healing are sought. Recently, several studies have demonstrated the beneficial effects of atelocollagen on tendon healing. In this study, poly(3,4-dihydroxy-L-phenylalanine) (pDOPA), a hydrophilic biomimetic material, was used to modify the hydrophobic surface of a PLGA suture (Vicryl, VC) for the stable coating of atelocollagen on its surface. The main objective was to fabricate an atelocollagen-coated VC suture and evaluate its performance in the healing of Achilles tendon using a rat model of open repair for ATR. Structural analyses of the surface-modified suture indicated that the collagen was successfully coated on the VC/pDOPA suture. Postoperative in vivo biomechanical analysis, histological evaluation, ultrastructural/morphological analyses, and western blotting confirmed that the tendons in the VC/pDOPA/Col group exhibit superior healing than those in the VC and VC/pDOPA groups after 1 and 6 weeks following the surgery. The this study suggests that atelocollagen-coated PLGA/pDOPA sutures are preferable for future medical applications, especially in the repair of ATR.

Enhancing genome editing in hPSCs through dual inhibition of DNA damage response and repair pathways.

Precise genome editing is crucial for establishing isogenic human disease models and ex vivo stem cell therapy from the patient-derived hPSCs. Unlike Cas9-mediated knock-in, cytosine base editor and prime editor achieve the desirable gene correction without inducing DNA double strand breaks. However, hPSCs possess highly active DNA repair pathways and are particularly susceptible to p53-dependent cell death. These unique characteristics impede the efficiency of gene editing in hPSCs. Here, we demonstrate that dual inhibition of p53-mediated cell death and distinct activation of the DNA damage repair system upon DNA damage by cytosine base editor or prime editor additively enhanced editing efficiency in hPSCs. The BE4stem system comprised of p53DD, a dominant negative p53, and three UNG inhibitor, engineered to specifically diminish base excision repair, improves cytosine base editor efficiency in hPSCs. Addition of dominant negative MLH1 to inhibit mismatch repair activity and p53DD in the conventional prime editor system also significantly enhances prime editor efficiency in hPSCs. Thus, combined inhibition of the distinct cellular cascades engaged in hPSCs upon gene editing could significantly enhance precise genome editing in these cells.

Novel Lipid Nanoparticles Stable and Efficient for mRNA Transfection to Antigen-Presenting Cells.

mRNA vaccines have emerged as a pivotal tool in combating COVID-19, offering an advanced approach to immunization. A key challenge with these vaccines is their need for extremely-low-temperature storage, which affects their stability and shelf life. Our research addresses this issue by enhancing the stability of mRNA vaccines through a novel cationic lipid, O,O'-dimyristyl-N-lysyl aspartate (DMKD). DMKD effectively binds with mRNA, improving vaccine stability. We also integrated phosphatidylserine (PS) into the formulation to boost immune response by promoting the uptake of these nanoparticles by immune cells. Our findings reveal that DMKD-PS nanoparticles maintain structural integrity under long-term refrigeration and effectively protect mRNA. When tested, these nanoparticles containing green fluorescent protein (GFP) mRNA outperformed other commercial lipid nanoparticles in protein expression, both in immune cells (RAW 264.7 mouse macrophage) and non-immune cells (CT26 mouse colorectal carcinoma cells). Importantly, in vivo studies show that DMKD-PS nanoparticles are safely eliminated from the body within 48 h. The results suggest that DMKD-PS nanoparticles present a promising alternative for mRNA vaccine delivery, enhancing both the stability and effectiveness of these vaccines.

Fracture gap and working length are important actionable factors affecting bone union after minimally invasive plate osteosynthesis for the treatment of simple diaphyseal or distal metaphyseal tibia fractures.

INTRODUCTION: Indirect reduction of minimally invasive plate osteosynthesis (MIPO) can often result in delayed union in tibia fractures. This study evaluated several factors in MIPO in relation to bone union. HYPOTHESIS: We hypothesized that the fracture gap, plate - tibia distance, or working length would have a substantial effect on the tibia union rate. MATERIALS AND METHODS: Forty-one patients with simple diaphyseal or distal metaphyseal tibia fractures who underwent internal fixation surgery using the MIPO technique were divided into two groups: patients with delayed union and patients without delayed union. Non-actionable factors involving AO/OTA classification, fibula fracture and actionable factors including postoperative fracture gap, plate - tibia distance, working length in relation to parameters of bone union were compared between the two groups. Also cumulative rates of bone union and risk factors of delayed union according to variables of interest were investigated. RESULTS: AO/OTA classification, site of fibula fracture, postoperative fracture gap, working length, and bone union rate of the two groups significantly differed (p<0.05). The cumulative rate of bone union during 1-year follow-up according to 43A tibia fracture, distal fibula fracture, fracture gap, and working length significantly differed between the two groups (p<0.05). By univariate Cox proportional hazards model, 43A tibia fracture, distal fibula fracture, facture gap, and short working length were risk factors for delayed union (p<0.05). DISCUSSION: Non-actionable factors involving AO/OTA classification, distal fibula fracture and actionable factors including postoperative fracture gap, working length were significant factors affecting bone union after MIPO. The present study indicated that small fracture gap and long working length during MIPO might facilitate bone healing in tibia fracture. LEVEL OF EVIDENCE: IV; single-center retrospective cohort study.

Oblique lateral interbody fusion with internal fixations in the treatment for cross-segment degenerative lumbar spine disease (L2-3 and L4-5) finite element analysis.

Multi-segmental lumbar degenerative disease, including intersegmental disc degeneration, is found in clinical practice. Controversy still exists regarding the treatment for cross-segment degeneration. Oblique Lateral Interbody Fusion (OLIF) with several internal fixations was used to treat cross-segment lumbar degenerative disease. A whole lumbar spine model was extracted from CT images of the whole lumbar spine of patients with lumbar degeneration. The L2-3 and L4-5 intervertebral spaces were fused with OLIF using modeling software, the Pedicle screws were performed on L2-3 and L4-5, and different internal fixations were performed on L3-4 in Finite Element (FE) software. Among the six 10 Nm moments of different directions, the L3-4 no surgery (NS) group had the relatively largest Range of Motion (ROM) in the whole lumbar spine, while the L2-5 Long segmental fixation (LSF)group had the smallest ROM and the other groups had similar ROM. The ROM in the L1-2 and L5-S1 was relatively close in the six group models, and the articular cartilage stress and disc stress on the L1-2 and L5-S1 were relatively close. In contrast, the L3-4 ROM differed relatively greatly, with the LSF ROM the smallest and the NS ROM the largest, and the L3-4 Coflex (Coflex) group more active than the L3-4 Bacfuse (Bacfuse) group and the L3-4 translaminar facet screw fixation (TFSF) group. The stress on the articular cartilage and disc at L3-4 was relatively greater in the NS disc and articular cartilage, and greater in the Coflex group than in the Bacfuse and TFSF groups, with the greatest stress on the internal fixation in the TFSF group, followed by the Coflex group, and relatively similar stress in the Bacfuse, LSF, and NS groups. In the TFSF group, the stress on the internal fixation was greater than the yield strength among different directional moments of 10 Nm, which means it is unsuitable to be an internal fixation. The LSF group had the greatest overall ROM, which may lead to postoperative low back discomfort. The NS group has the greatest overall ROM, but its increased stress on the L3-4 disc and articular cartilage may lead to accelerated degeneration of the L3-4 disc and articular cartilage. The Coflex and Bacfuse groups had a reduced L3-4 ROM but a greater stress on disc compared to the LSF group, which may lead to disc degeneration in the long term. However, their stress on the articular cartilage was relatively low. Coflex and Bacfuse can still be considered better surgical options.

Brown Sequard syndrome in a patient with Klippel-Feil syndrome following minor trauma: a case report and literature review.

BACKGROUND: There are some cases of Klippel-Feil syndrome with spinal cord injury in clinical work. However, there is no literature report on Brown-Sequard syndrome after trauma. We report a case of Brown-Sequard syndrome following minor trauma in a patient with KFS type III. Her Brown-Sequard syndrome is caused by Klippel-Feil syndrome. CASE PRESENTATION: We found a 38-year-old female patient with KFS in our clinical work. She was unconscious on the spot following a minor traumatic episode. After treatment, her whole body was numb and limb activity was limited. Half an hour later, she felt numb and weak in the right limb and weak in the left limb. She had no previous hypertension, diabetes, or coronary heart disease. After one-month treatment of medication, hyperbaric oxygen, rehabilitation, and acupuncture in our hospital, her muscle strength partially recovered, but the treatment effect was still not satisfactory. Then, she underwent surgical treatment and postoperative comprehensive treatment, and rehabilitation training. She was able to take care of herself with assistance, and her condition improved from grade B to grade D according to the ASIA (ASIA Impairment Scale) classification. CONCLUSION: KFS, also known as short neck deformity, is a kind of congenital deformity characterized by impaired formation and faulty segmentation of the cervical spine, often associated with abnormalities of other organs. The cervical deformity in patients with KFS can alter the overall mechanical activity of the spine, as well as the compensatory properties of the spine for decelerating and rotatory forces, thus increasing the chance of spinal cord injury (SCI) following trauma. Many mechanisms can make patients more susceptible to injury. Increased range of motion of the segment adjacent to the fused vertebral body may lead to slippage of the adjacent vertebral body and altered disc stress, as well as cervical instability. SCI can result in complete or incomplete impairment of motor, sensory and autonomic nervous functions below the level of lesion. This woman presented with symptoms of BSS, a rare neurological disorder with incomplete SCI. Judging from the woman's symptoms, we concluded that previously she had KFS, which resulted in SCI without fracture and dislocation following minor trauma, with partial BSS. After the comprehensive treatment of surgery, hyperbaric oxygen, rehabilitation therapy, and neurotrophic drugs, two years later, we found her symptoms significantly improved, with ASIA Impairment Scale from grade B to grade D, and her ability to perform activities of daily living with aids.

A Comparative Analysis of Pain Control Methods after Ankle Fracture Surgery with a Peripheral Nerve Block: A Single-Center Randomized Controlled Prospective Study.

Background and Objectives: Patients experience severe pain after surgical correction of ankle fractures. Although their exact mechanism is unknown, dexamethasone and epinephrine increase the analgesic effect of anesthetics in peripheral nerve blocks. This study aimed to compare the postoperative pain control efficacy of peripheral nerve blocks with ropivacaine combined with dexamethasone/epinephrine and peripheral nerve blocks with only ropivacaine and added patient-controlled analgesia in patients with ankle fractures. Materials and Methods: This randomized, controlled prospective study included patients aged 18-70 years surgically treated for ankle fractures between December 2021 and September 2022. The patients were divided into group A (n = 30), wherein pain was controlled using patient-controlled analgesia after lower extremity peripheral nerve block, and group B (n = 30), wherein dexamethasone/epinephrine was combined with the anesthetic solution during peripheral nerve block. In both groups, ropivacaine was used as the anesthetic solution for peripheral nerve block, and this peripheral nerve block was performed just before ankle surgery for the purpose of anesthesia for surgery. Pain (visual analog scale), patient satisfaction, and side effects were assessed and compared between the two groups. Results: The patients' demographic data were similar between groups. Pain scores were significantly lower in group B than in group A postoperatively. Satisfaction scores were significantly higher in group B (p = 0.003). There were no anesthesia-related complications in either group. Conclusions: Dexamethasone and epinephrine as adjuvant anesthetic solutions can effectively control pain when performing surgery using peripheral nerve blocks for patients with ankle fractures.

Risk factors affecting severe thoracic injuries in motor vehicle collisions based on age group and collision directions.

OBJECTIVE: This study aimed to investigate the effect of age and collision direction on the severity of thoracic injuries based on a real-world crash database. METHODS: This was a retrospective, observational study. We used the Korean In-Depth Accident Study (KIDAS) database, which was collected from crash injury patients who visited emergency medical centers between January 2011 and February 2022 in Korea. Among the 4520 patients enrolled in the database, we selected 1908 adult patients with abbreviated injury scale (AIS) scores between 0 and 6 in the thoracic region. We classified patients with an AIS score of 3 or higher into the severe injury group. RESULTS: The incidence rate of severe thoracic injuries due to motor vehicle accidents was 16.4%. Between the severe and non-severe thoracic injury groups, there were significant differences in sex, age, collision direction, crash object, seatbelt use, and delta-V parameters. Among the age groups, over 55 years occupants had a higher risk in the thoracic regions than those under 54 years occupants. The risk of severe thoracic injury was highest in near-side collisions in all collision directions. Far-side and rear-end collisions showed a lower risk than frontal collisions. Occupants with unfastened seatbelts were at greater risk. CONCLUSIONS: The risk of severe thoracic injury is high in near-side collisions among elderly occupants. However, the risk of injury for elderly occupants increases in a super-aging society. To reduce thoracic injury, safety features made for elderly occupants in near-side collisions are required.

Acetate-Mediated Odorant Receptor OR51E2 Activation Results in Calcitonin Secretion in Parafollicular C-Cells: A Novel Diagnostic Target of Human Medullary Thyroid Cancer.

Medullary thyroid cancer originates from parafollicular C-cells in the thyroid. Despite successful thyroidectomy, localizing remnant cancer cells in patients with elevated calcitonin and carcinoembryonic antigen levels remains a challenge. Extranasal odorant receptors are expressed in cells from non-olfactory tissues, including C-cells. This study evaluates the odorant receptor signals from parafollicular C-cells, specifically, the presence of olfactory marker protein, and further assesses the ability of the protein in localizing and treating medullary thyroid cancer. We used immunohistochemistry, immunofluorescent staining, Western blot, RNA sequencing, and real time-PCR to analyze the expression of odorant receptors in mice thyroids, thyroid cancer cell lines, and patient specimens. We used in vivo assays to analyze acetate binding, calcitonin secretion, and cAMP pathway. We also used positron emission tomography (PET) to assess C11-acetate uptake in medullary thyroid cancer patients. We investigated olfactory marker protein expression in C-cells in patients and found that it co-localizes with calcitonin in C-cells from both normal and cancer cell lines. Specifically, we found that OR51E2 and OR51E1 were expressed in thyroid cancer cell lines and human medullary thyroid cancer cells. Furthermore, we found that in the C-cells, the binding of acetate to OR51E2 activates its migration into the nucleus, subsequently resulting in calcitonin secretion via the cAMP pathway. Finally, we found that C11-acetate, a positron emission tomography radiotracer analog for acetate, binds competitively to OR51E2. We confirmed C11-acetate uptake in cancer cells and in human patients using PET. We demonstrated that acetate binds to OR51E2 in C-cells. Using C11-acetate PET, we identified recurrence sites in post-operative medullary thyroid cancer patients. Therefore, OR51E2 may be a novel diagnostic and therapeutic target for medullary thyroid cancer.

Olfactory marker protein regulates adipogenesis via the cAMP-IκBα pathway.

Olfactory marker protein (OMP) regulates olfactory transduction and is also expressed in adipose tissue. Since it serves as a regulatory buffer for cyclic AMP (cAMP) levels, we hypothesized that it plays a role in modulating adipocyte differentiation. To determine the role of OMP in adipogenesis, we examined the differences in body weight, adipose tissue mass, and adipogenic or thermogenic gene expression between high-fat diet-fed control and Omp-knockout (KO) mice. cAMP production, adipogenic gene expression, and cAMP response element binding protein (CREB) phosphorylation were measured during the differentiation of 3T3-L1 preadipocytes and mouse embryonic fibroblasts (MEFs). RNA sequencing was performed to determine the gene expression patterns responsible for the reduction in adipogenesis when Omp was deleted. Body weight, adipose tissue mass, and adipocyte size decreased in Omp-KO mice. Furthermore, cAMP production and CREB phosphorylation reduced during adipogenesis induced in Omp-/- MEFs, and the Nuclear factor kappa B was activated due to significantly reduced expression of its inhibitor. Collectively, our results suggest that loss of OMP function inhibits adipogenesis by affecting adipocyte differentiation.

Comparison of Intermediate-Term Clinical Outcomes Between Medial and Lateral Osteochondral Lesions of the Talus Treated With Autologous Osteochondral Transplantation.

BACKGROUND: The conventional operative method to treat an osteochondral lesion of the talus (OLT) is through bone marrow stimulation (BMS). Autologous osteochondral transplantation (AOT) is being used as an alternative option in cases with a large OLT, accompanying subchondral cyst, and/or failed BMS. We aimed to compare the intermediate-term clinical and radiologic results between medial and lateral OLTs after an AOT procedure. METHODS: Among the patients who underwent AOT, 45 cases with at least 3 years' follow-up were included in this retrospective study. We had 15 cases of lateral lesions and selected 30 cases of medial lesions matched for age and gender. Lateral lesions were resurfaced without an osteotomy; medial lesion resurfacing was combined with a medial malleolar osteotomy. Clinical assessment was performed using the Foot and Ankle Outcome Score (FAOS) and Foot and Ankle Ability Measure (FAAM). Radiographic assessment included the irregularity of articular surface (subchondral plate), the progression of degenerative arthritis, and the change of the talar tilt. RESULTS: The mean FAOS and FAAM scores significantly improved after surgery in both groups. Up to 1 year postoperatively, there was significant difference in FAAM scores between the both groups (mean 75.3 points in medial group and 87.2 points in lateral group, P < .001). Delayed union or malunion of the malleolar osteotomy was found in 4 cases (13%) in the medial group. In addition, the progression of joint degeneration was observed in 3 cases (10%) in the medial group. There were no significant differences in the irregularity of articular surface and the change of talar tilt between both groups. CONCLUSION: A comparison between medial and lateral OLTs treated with AOT demonstrated comparable intermediate-term clinical outcomes. However, patients with medial OLT required a longer period to restore ability for daily and sport activities. In addition, we found more complications and higher rate of progression in the radiologic arthritis grade after medial malleolar osteotomy. LEVEL OF EVIDENCE: Level IV, retrospective comparative study.

Risk Factors for Contralateral Tendon Rupture in Patients With Acute Achilles Tendon Rupture.

The present study was performed to determine the incidence and risk factors of contralateral Achilles tendon rupture after an initial tendon rupture, and to identify the associated patient characteristics. Medical records of 181 adult patients with acute Achilles tendon rupture were reviewed. We investigated the risk factors for contralateral Achilles tendon rupture and calculated the incidence density (per 100 person-years), survival rate, hazard ratios, and 95% confidence intervals. The risk factors were extracted, including blood type, age, body mass index (BMI), occupation, underlying comorbidities, history of alcohol intake or smoking, injury mechanism, and fluoroquinolone antibiotic or steroid use. Military personnel and manual laborers, including farmers and firefighters were considered to have an occupation involving physical activity. Ten patients (5.5%) were identified as having nonsimultaneous, contralateral Achilles tendon rupture a mean of 3.3 years (range 1.0-8.3 years) after the initial tendon rupture. The incidence density of contralateral tendon rupture was 0.89 per 100 person-years. The 8-year survival rate of contralateral tendon rupture was 92.2%. Unadjusted and adjusted hazard ratios (with 95% confidence intervals, p value) of blood type O were 3.71 (1.07-12.82, p = .038) and 2.90 (0.81-10.32, p = .101), respectively, and those of occupations involving physical activity were 5.87 (1.64-20.98, p = .006) and 4.69 (1.27-17.28, p = .02), respectively. Based on the present data, blood type O and occupations involving physical activity are significantly associated with an increased risk of contralateral tendon rupture in adult patients who have sustained Achilles tendon rupture.

Difference in Joint Stability Between Small Posterior Malleolar Fragments With Fixation and Those Without Fixation: A Biomechanical Cadaver Study.

The indication for the surgical treatment of ankle fractures that involve a posterior malleolar fragment remains controversial. This cadaver study assessed the biomechanical results of rotation stiffness of Haraguchi type 1 posterior malleolar fragments with or without cannulated screw fixation. Twelve anatomic lower-extremity specimens from 6 cadavers were tested. Six right legs were subjected to posterior malleolus osteotomy (Haraguchi type I) followed with (group A; n = 3) or without (group B; n = 3) fixation using a cannulated screw. Ankle joint stability was measured under both external rotation force and axial loading, and the passive resistive torque was measured in both groups. The mean torque value in group A was 0.1093 Nm/º, while that in group B was 0.0537 Nm/º. There was a significant intergroup difference (p = .004). In group B, the torque value was further increased in the latter rotation period (about 40-60 degrees). Group A proved more stable under experimental conditions than group B. Fixation in type I posterior malleolar fragments produced improved stability in ankle rotation, even for posterior malleolar fragments involving <25% of the articular surface, and has been considered an effective aid in treatment.

Tumor-Targeted Erythrocyte Membrane Nanoparticles for Theranostics of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) cells do not contain various receptors for targeted treatment, a reason behind the poor prognosis of this disease. In this study, biocompatible theranostic erythrocyte-derived nanoparticles (EDNs) were developed and evaluated for effective early diagnosis and treatment of TNBC. The anti-cancer drug, doxorubicin (DOX), was encapsulated into the EDNs and diagnostic quantum dots (QDs) were incorporated into the lipid bilayers of EDNs for tumor bio-imaging. Then, anti-epidermal growth factor receptor (EGFR) antibody molecules were conjugated to the surface of EDNs for TNBC targeting (iEDNs). According to the confocal microscopic analyses and biodistribution assay, iEDNs showed a higher accumulation in EGFR-positive MDA-MB-231 cancers in vitro as well as in vivo, compared to untargeted EDNs. iEDNs containing doxorubicin (iEDNs-DOX) showed a stronger inhibition of target tumor growth than untargeted ones. The resulting anti-EGFR iEDNs exhibited strong biocompatibility, prolonged blood circulation, and efficient targeting of TNBC in mice. Therefore, iEDNs may be used as potential TNBC-targeted co-delivery systems for therapeutics and diagnostics.

How to Effectively Monitor Aging Patients with Chronic Hepatitis B: A Review.

Hepatitis B virus (HBV) infection is a major global public health challenge associated with significant morbidity and mortality. Due to worldwide population aging, HBV infection in the elderly will become increasingly prevalent. Effective universal vaccination programs exist but these are largely targeted towards the younger population. Therefore, the elderly population remains at risk of higher disease burden. New diagnoses of HBV infection in the elderly are usually asymptomatic chronic infections which increases their risk of developing cirrhosis, hepatocellular carcinoma, and liver disease-related mortality, especially if left untreated. Physiological changes and the increasing prevalence of multimorbidity associated with aging also potentially worsen outcomes in elderly patients with chronic HBV infection. Therefore, this cohort of patients should be monitored closely and effectively. Current international clinical practice guidelines unfortunately do not provide hard treatment endpoints specific to elderly patients with chronic HBV infection. Management of these patients is complex and requires an individualized approach. Multiple factors such as physiological changes, comorbidities, compliance, treatment tolerability and efficacy, burden of treatment, and realistic treatment goals need to be considered. Shared decision-making between patient and clinician is essential to ensure that the final decision for or against treatment aligns with the patient's values and preferences. This review article aims to summarize the monitoring and management of chronic HBV infection in the aging population.

Anatomic anterior talofibular ligament repair augmented with suture-tape for chronic ankle instability with poor quality of remnant ligamentous tissue.

PURPOSE: Because modified Broström procedure provides a restoration of mechanical stability by reinforcing attenuated host tissue, poor quality of remnant ligamentous tissue is considered as a prognostic factor for ligament repair surgery. The purpose of this study was to assess the intermediate-term clinical results after anatomic anterior talofibular ligament repair augmented with suture-tape for chronic lateral ankle instability (CLAI) with poor quality of ligament remnants. METHODS: 64 patients with the insufficient anterior talofibular ligament confirmed by preoperative magnetic resonance image and intraoperative inspection were followed for ≥3 years after the augmented anterior talofibular ligament repair. The clinical outcomes were assessed with the Foot and Ankle Outcome Score, Foot and Ankle Ability Measure. Measurements on stress radiographs were performed to assess the changes of mechanical instability. To identify the changes of functional ankle instability, postural control ability was analysed with single leg stance test. RESULT: Foot and Ankle Outcome Score and Foot and Ankle Ability Measure scores improved from preoperative mean 58.3 and 53.6 points to 90.2 and 88.7 points at final followup, respectively (p < 0.001). Talar tilt angle and anterior talar translation improved from preoperative mean 16.5° and 13.4 mm to 3.2° and 4.4 mm at final followup, respectively (p < .001). Two patients (3.1%) showed a recurrence of instability. Although balance retention time improved from preoperative mean 3.9-6.2 seconds at final followup (p < .001), a significant side-to-side difference was found. CONCLUSION: Anatomic anterior talofibular ligament repair augmented with suture-tape appears to be a useful surgical option for CLAI with poor quality of ligament remnants at intermediate-term followup. Through anatomic repair of attenuated ligaments and suture-tape augmentation, this combined procedure can provide the reliable restoration of mechanical stability and advantages of the anatomic ligament repair. Postural control deficit compared to the uninjured ankle supports a necessity of continuous proprioceptive-oriented rehabilitation.