Updated Reference Intervals for Alanine Aminotransferase in a Metabolically and Histologically Normal Population.

BACKGROUND & AIMS: This study aims to reevaluate upper reference limit (URL) for alanine aminotransferase (ALT) by considering the changing epidemiology of major liver diseases. We employed histological and metabolic parameters in Asian living liver donors. METHODS: We performed a retrospective analysis of 5455 potential living liver donors from 2005 to 2019. Participants were screened for hepatitis B, C, HIV, and alcohol use. Histologically and metabolically healthy participants were assessed using the Prati criteria (body mass index <23 kg/m2, triglyceride ≤200 mg/dL, fasting glucose ≤105 mg/dL, total cholesterol ≤220 mg/dL). The updated ALT-URL was determined as the 95th percentile among participants without hepatic steatosis and who met the Prati criteria. RESULTS: The median age was 30 years, with a male predominance (66.2%). Among 5455 participants, 3162 (58.0%) showed no hepatic steatosis, with 1553 (49.1%) meeting both the criteria for no steatosis and the Prati criteria for metabolic health. The updated URL for ALT in these participants was 34 U/L for males and 22 U/L for females, which was significantly lower than conventionally accepted values. Using this revised ALT-URL, 72.8% of males with ALT levels ≥34 U/L and 55.0% of females with ALT levels ≥22 U/L showed signs of steatosis, whereas 32.7% of males and 22.2% of females met the criteria for metabolic syndrome. CONCLUSIONS: Our study provided the newly established reference intervals for ALT levels in a metabolically and histologically verified Asian population. The proposed URL for ALT are 34 U/L and 22 U/L for males and females, respectively.

Withaferin A mitigates metastatic traits in human oral squamous cell carcinoma caused by aberrant claudin-1 expression.

Abnormal expression of claudin-1 (CLDN1) has important roles in carcinogenesis and metastasis in various cancers. The role of CLDN1 in human oral squamous cell carcinoma (OSCC) remains unknown. Here, we report the functional role of CLDN1 in metastasis of human OSCC, as a potential target regulated by withaferin A. From gene expression profiling with microarray technology, we found that the majority of notable differentially expressed genes were classified into migration/invasion category. Withaferin A impaired the motility of human OSCC cells in vitro and suppressed metastatic nodule formation in an in vivo metastasis model, both associated with reduced CLDN1. CLDN1 overexpression enhanced metastatic nodule formation in vivo, resulting in severe metastatic lesions in lung tissue. Moreover, CLDN1 expression was positively correlated to lymphatic metastasis in OSCC patients. The impaired motility of human OSCC cells upon withaferin A treatment was restored by CLDN1 overexpression. Furthermore, upregulation of let-7a induced by withaferin A was inversely correlated to CLDN1 expression. Overall, these give us an insight into the function of CLDN1 for prognosis and treatment of human OSCC, substantiating further investigation into the use of withaferin A as good anti-metastatic drug candidate.

Performance evaluation of serum PIVKA-II measurement using HISCL-5000 and a method comparison of HISCL-5000, LUMIPULSE G1200, and ARCHITECT i2000.

BACKGROUND: Protein induced by vitamin K antagonist-II (PIVKA-II), in addition to alpha-fetoprotein, is a useful tumor marker for diagnosis of hepatocellular carcinoma (HCC). We evaluated the analytical performance of the HISCL-5000 analyzer (Sysmex Corporation) in the measurement of serum PIVKA-II. METHODS: We evaluated the precision and linearity of PIVKA-II assays using the HISCL-5000 analyzer. Methods using HISCL-5000, LUMIPULSE G1200 (Fujirebio Diagnostics), and ARCHITECT i2000 (Abbott Diagnostics) were compared according to the guidelines of the Clinical and Laboratory Standards Institute. A total of 501 subjects (median age 59 years, age range 24-90 years) were enrolled. Among them, 335 were HCC patients, 46 were patients with non-HCC liver disease, and 120 were healthy individuals. Non-HCC liver disease included liver cirrhosis, chronic hepatitis, HBV or HCV carrier, hepatic adenoma, and intrahepatic cholangiocarcinoma. RESULTS: Repeatability (%CV) in low- and high-level controls and pooled serum was 2.81%-10.30%, and within-laboratory precision was 4.24%-8.86%. In a linearity test, the coefficient of determination (R2 ) was 0.9957, ranging from 11 to 69 897 mAU/mL. In comparison, the coefficient of correlation (r) was 0.9561-0.9644, agreement was 93.4%-97.6%, and the κ value was 0.855-0.945 among the three analyzers. About 99.2% of healthy individuals and 84.8% of non-HCC liver disease patients were below the cutoff value (40 mAU/mL) on HISCL-5000. CONCLUSIONS: A PIVKA-II assay using HISCL-5000 showed acceptable analytical performance including precision, linearity, and method comparison. This indicates that HISCL-5000 can be potentially helpful in clinical laboratories.

Differences of Self-Control, Daily Life Stress, and Communication Skills between Smartphone Addiction Risk Group and General Group in Korean Nursing Students.

Concerns about smartphone addiction have been raised as the use time of and dependence on the smartphone is increasing. This study were to examine the differences of self-control, daily life stress, and communication skills between smartphone addiction risk group and general group in nursing students, South Korea. A cross-sectional descriptive design was adopted. Samples were total 139 nursing students (addictive risk: n = 40, general: n = 99) at G and B cities in South Korea. Measures were general characteristics form, self-control scale in Korean version, daily life stress scale for college students, and Global Interpersonal Communication Competence Scale (GICC). There were significant differences on self-control (t = 3.02, p = 0.003) and daily life stress (t = 3.56, p < 0.001), but there was no significant difference on communication skills (t = 1.72, p = 0.088) between two groups. Nursing students in smart phone addiction risk group had worse self-control and higher daily life stress than nursing students in general group. The preventive education programs for healthy smartphone use of Korean nursing students are needed.

Comparative Evaluation of QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus in Diagnosis of Latent Tuberculosis Infection in Immunocompromised Patients.

QuantiFERON-TB Gold Plus (QFT-Plus) is a new-generation QuantiFERON-TB Gold In-Tube (QFT-GIT) assay which has two antigen-coated tubes called TB1, which contains long peptides derived from ESAT-6 and CFP-10, and TB2, which contains the same components as TB1 and additional short peptides which potentially stimulate CD8+ T cells through the presentation of major histocompatibility complex class I. This is the first study to compare QFT-Plus and QFT-GIT for use in the diagnosis of latent tuberculosis infection (LTBI) among immunocompromised patients in the Republic of Korea. Among 317 consecutive patients who underwent screening for LTBI before solid organ or hematopoietic stem cell transplantation and tumor necrosis factor alpha inhibitor treatment, LTBI was identified in 92 (29.0%) and 88 (27.8%) patients by QFT-GIT and QFT-Plus, respectively. The rate of concordance between QFT-GIT and QFT-Plus was 93.7% (κ value, 0.860), and the indeterminate rate (3.2%) was similar between QFT-GIT and QFT-Plus. Of 20 (6.3%) samples with discordant results, 11 (55.0%) and 7 (35.0%) were positive by QFT-GIT alone and QFT-Plus alone, respectively, and 2 (15.0%) were indeterminate by each assay. The interferon gamma level in samples with discordant results ranged from 0.39 to 1.10 IU/ml, except for one sample, in which the gamma interferon level was 2.97 IU/ml only in TB2. Conclusively, there was a high degree of agreement between the results of QFT-GIT and QFT-Plus for the screening of immunocompromised patients for LTBI. The reactivity in TB2 contributed substantially to the difference between QFT-GIT and QFT-Plus, particularly in solid organ transplant candidates. The significance of the discrete responses in TB1 and TB2 of QFT-Plus needs to be explored further by means of an immunological and clinical approach in different patient groups and clinical settings.

Performance evaluation of the QMAC-dRAST for staphylococci and enterococci isolated from blood culture: a comparative study of performance with the VITEK-2 system.

Objectives: To evaluate the performance of a rapid antimicrobial susceptibility testing (AST) platform based on microfluidic chip technology, the QMAC-dRAST, which enables AST from colony isolates or positive blood culture broth (PBCB), and to compare the performance of the QMAC-dRAST for staphylococci and enterococci with that of the VITEK-2 system based on reference broth microdilution (BMD). Methods: A total of 110 staphylococcal and enterococcal isolates from blood cultures were included. AST was performed directly using the QMAC-dRAST with PBCB. Thereafter, colony isolates derived from subculture of PBCB were used for the QMAC-dRAST, the VITEK-2 system and BMD. Results: The overall agreement between the QMAC-dRAST with PBCB and BMD was 91.5%. There were 1.2% very major errors (VMEs), 4.3% major errors (MEs) and 5.4% minor errors (mEs). The QMAC-dRAST with colony isolates yielded 94.6% agreement and error rates of 1.0% VMEs, 1.8% MEs and 4.0% mEs. The VITEK-2 system showed 96.2% agreement and error rates of 2.3% VMEs, 0.5% MEs and 2.6% mEs. The incubation time in the QMAC-dRAST was significantly shorter than in the VITEK-2 system (median of 6 versus 10 h; P < 0.0001). Conclusions: The QMAC-dRAST system provided rapid results and represents an alternative to conventional AST methods. The QMAC-dRAST with colony isolates produced more reliable results for staphylococci and enterococci than the QMAC-dRAST with PBCB. The QMAC-dRAST system also performed comparably to BMD and the VITEK-2 system.

Intestinal Dysbiosis, Barrier Dysfunction, and Bacterial Translocation Account for CKD-Related Systemic Inflammation.

CKD associates with systemic inflammation, but the underlying cause is unknown. Here, we investigated the involvement of intestinal microbiota. We report that collagen type 4 α3-deficient mice with Alport syndrome-related progressive CKD displayed systemic inflammation, including increased plasma levels of pentraxin-2 and activated antigen-presenting cells, CD4 and CD8 T cells, and Th17- or IFNγ-producing T cells in the spleen as well as regulatory T cell suppression. CKD-related systemic inflammation in these mice associated with intestinal dysbiosis of proteobacterial blooms, translocation of living bacteria across the intestinal barrier into the liver, and increased serum levels of bacterial endotoxin. Uremia did not affect secretory IgA release into the ileum lumen or mucosal leukocyte subsets. To test for causation between dysbiosis and systemic inflammation in CKD, we eradicated facultative anaerobic microbiota with antibiotics. This eradication prevented bacterial translocation, significantly reduced serum endotoxin levels, and fully reversed all markers of systemic inflammation to the level of nonuremic controls. Therefore, we conclude that uremia associates with intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation, which trigger the state of persistent systemic inflammation in CKD. Uremic dysbiosis and intestinal barrier dysfunction may be novel therapeutic targets for intervention to suppress CKD-related systemic inflammation and its consequences.

ABO Mistyping of cis-AB Blood Group by the Automated Microplate Technique.

BACKGROUND: The cis-AB phenotype, although rare, is the relatively most frequent of ABO subgroups in Koreans. To prevent ABO mistyping of cis-AB samples, our hospital has applied a combination of the manual tile method with automated devices. Herein, we report cases of ABO mistyping detected by the combination testing system. METHODS: Cases that showed discrepant results by automated devices and the manual tile method were evaluated. These samples were also tested by the standard tube method. The automated devices used in this study were a QWALYS-3 and Galileo NEO. Exons 6 and 7 of the ABO gene were sequenced. RESULTS: 13 cases that had the cis-AB allele showed results suggestive of the cis-AB subgroup by manual methods, but were interpreted as AB by either automated device. This happened in 87.5% of these cases by QWALYS-3 and 70.0% by Galileo NEO. Genotyping results showed that 12 cases were ABO*cis-AB01/ABO*O01 or ABO*cis-AB01/ABO*O02, and one case was ABO*cis-AB01/ ABO*A102. CONCLUSION: Cis-AB samples were mistyped as AB by the automated microplate technique in some cases. We suggest that the manual tile method can be a simple supplemental test for the detection of the cis-AB phenotype, especially in countries with relatively high cis-AB prevalence.

Down-regulation of Akt by methanol extracts of Impatiens balsamina L. promotes apoptosis in human oral squamous cell carcinoma cell lines.

BACKGROUND: The apoptotic activity of methanol extracts of Impatiens balsamina L. (MEIB) and related mechanisms in human oral squamous cell carcinoma (OSCC) cells have been systematically investigated. METHODS: The effects of MEIB on human OSCC cell lines were investigated using trypan blue exclusion assay, MTS assay, Western blot, 4'-6-diamidino-2-phenylindole (DAPI) staining, Live/Dead assay, Immunohistochemistry, reverse transcription-polymerase chain reaction, and promoter assay. RESULTS: MEIB decreased cell viability and induced apoptosis in HSC-4 cells. Higher levels of p-Akt expression were observed in OSCC than in normal oral mucosa (NOM), and it correlated with poor survival of the patients. MEIB dephosphorylated p-Akt and decreased Akt expression through proteasome-dependent degradation. LY294002 (PI3K inhibitor) decreased p-Akt and Akt, resulting in enhancing MEIB-induced apoptosis. MEIB down-regulated the expression level of survivin protein at the transcriptional level and YM155 (survivin inhibitor) decreased survivin, which facilitated MEIB-induced apoptosis. MEIB and LY294002 significantly increased Bax, thereby inducing the conformational change, mitochondrial translocation, and oligomerization. In addition, MEIB-induced growth inhibition and apoptosis in OSC-20, another human OSCC cells were mediated by regulating Akt and it downstream targets, survivin and Bax. CONCLUSIONS: These results suggest that MEIB may serve as a potential drug candidate for the treatment of human OSCC.

Macrophage phenotype controls long-term AKI outcomes--kidney regeneration versus atrophy.

The mechanisms that determine full recovery versus subsequent progressive CKD after AKI are largely unknown. Because macrophages regulate inflammation as well as epithelial recovery, we investigated whether macrophage activation influences AKI outcomes. IL-1 receptor-associated kinase-M (IRAK-M) is a macrophage-specific inhibitor of Toll-like receptor (TLR) and IL-1 receptor signaling that prevents polarization toward a proinflammatory phenotype. In postischemic kidneys of wild-type mice, IRAK-M expression increased for 3 weeks after AKI and declined thereafter. However, genetic depletion of IRAK-M did not affect immunopathology and renal dysfunction during early postischemic AKI. Regarding long-term outcomes, wild-type kidneys regenerated completely within 5 weeks after AKI. In contrast, IRAK-M(-/-) kidneys progressively lost up to two-thirds of their original mass due to tubule loss, leaving atubular glomeruli and interstitial scarring. Moreover, M1 macrophages accumulated in the renal interstitial compartment, coincident with increased expression of proinflammatory cytokines and chemokines. Injection of bacterial CpG DNA induced the same effects in wild-type mice, and TNF-α blockade with etanercept partially prevented renal atrophy in IRAK-M(-/-) mice. These results suggest that IRAK-M induction during the healing phase of AKI supports the resolution of M1 macrophage- and TNF-α-dependent renal inflammation, allowing structural regeneration and functional recovery of the injured kidney. Conversely, IRAK-M loss-of-function mutations or transient exposure to bacterial DNA may drive persistent inflammatory mononuclear phagocyte infiltrates, which impair kidney regeneration and promote CKD. Overall, these results support a novel role for IRAK-M in the regulation of wound healing and tissue regeneration.

Toll-like receptor 4-induced IL-22 accelerates kidney regeneration.

AKI involves early Toll-like receptor (TLR)-driven immunopathology, and resolution of inflammation is needed for rapid regeneration of injured tubule cells. Notably, activation of TLRs also has been implicated in epithelial repair. We hypothesized that TLR signaling drives tubule regeneration after acute injury through the induction of certain ILs. Systematic screening in vitro identified IL-22 as a candidate proregeneratory factor in primary tubular cell recovery, and IL-22 deficiency or IL-22 blockade impaired post-ischemic tubular recovery after AKI in mice. Interstitial mononuclear cells, such as dendritic cells and macrophages, were the predominant source of IL-22 secretion, whereas IL-22 receptor was expressed by tubular epithelial cells exclusively. Depleting IL-22-producing cells during the healing phase impaired epithelial recovery, which could be rescued entirely by reconstituting mice with IL-22. In vitro, necrotic tubular cells and oxidative stress induced IL-22 secretion selectively through TLR4. Although TLR4 blockade during the early injury phase prevented tubular necrosis and AKI, TLR4 blockade during the healing phase suppressed IL-22 production and impaired kidney regeneration. Taken together, these results suggest that necrotic cell-derived TLR4 agonists activate intrarenal mononuclear cells to secrete IL-22, which accelerates tubular regeneration and recovery in AKI.

Smectic assemblies in C3-symmetric hexa-alkylated liquid crystals: transformation from smectogen to discogen via hydrogen bonding.

In this paper, we report a C3-symmetric liquid crystal (LC) with sixfold alkyl peripheries exhibiting an unusual smectic E-like organization in the LC state. Based on conformational considerations, the smectic assembly is attributed to the formation of an endo-type Y conformer of asymmetric triazolyl and benzylic groups that cannot be accessed in other C3-symmetric molecules exclusively showing columnar assemblies. The Y conformers form a two-dimensional oblique lattice in the aromatic layers of the ordered smectic phase. In addition, the Y-shaped molecule in the smectic phases can change into a circular shape by the 1 : 1 hydrogen-bonding interaction with a gallic acid derivative, which leads to a hexagonal columnar LC phase. The triazole-based LC design concept proves the smectic LC assembly in the C3-symmetric system, and provides the supramolecular manipulation of LC morphologies.

Podocyte loss involves MDM2-driven mitotic catastrophe.

Podocyte apoptosis as a pathway of podocyte loss is often suspected but rarely detected. To study podocyte apoptosis versus inflammatory forms of podocyte death in vivo, we targeted murine double minute (MDM)-2 for three reasons. First, MDM2 inhibits p53-dependent apoptosis; second, MDM2 facilitates NF-κB signalling; and third, podocytes show strong MDM2 expression. We hypothesized that blocking MDM2 during glomerular injury may trigger p53-mediated podocyte apoptosis, proteinuria, and glomerulosclerosis. Unexpectedly, MDM2 blockade in early adriamycin nephropathy of Balb/c mice had the opposite effect and reduced intra-renal cytokine and chemokine expression, glomerular macrophage and T-cell counts, and plasma creatinine and blood urea nitrogen levels. In cultured podocytes exposed to adriamycin, MDM2 blockade did not trigger podocyte death but induced G2/M arrest to prevent aberrant nuclear divisions and detachment of dying aneuploid podocytes, a feature of mitotic catastrophe in vitro and in vivo. Consistent with these observations, 12 of 164 consecutive human renal biopsies revealed features of podocyte mitotic catastrophe but only in glomerular disorders with proteinuria. Furthermore, delayed MDM2 blockade reduced plasma creatinine levels, blood urea nitrogen, tubular atrophy, interstitial leukocyte numbers, and cytokine expression as well as interstitial fibrosis. Together, MDM2-mediated mitotic catastrophe is a previously unrecognized variant of podocyte loss where MDM2 forces podocytes to complete the cell cycle, which in the absence of cytokinesis leads to podocyte aneuploidy, mitotic catastrophe, and loss by detachment. MDM2 blockade with nutlin-3a could be a novel therapeutic strategy to prevent renal inflammation, podocyte loss, glomerulosclerosis, proteinuria, and progressive kidney disease.

The effects of recombinant human bone morphogenetic protein-2-loaded tricalcium phosphate microsphere-hydrogel composite on the osseointegration of dental implants in minipigs.

Bone formation in tooth defect areas and the osseointegration of dental implants are very important for successful dental implant surgery. The aim of the present study was to assess the strengthening effect of a ß-TCP microsphere-hydrogel composite containing recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone healing and implant osseointegration. The molars and premolars on the left and right sides of the maxilla were extracted from six male minipigs, and dental implants were placed using either the ß-TCP microsphere-hydrogel carrier alone or the carrier loaded with rhBMP-2 (500 µg). The animals were kept alive for a further 8 weeks. The molars and premolars from the left and the right sides of the mandibles of another six minipigs were extracted, and the animals were kept alive for 4 weeks. Two 5-mm-diameter bone defects were then made on both sides of the mandible. The defects were filled with saline, ß-TCP microsphere-hydrogel carrier, or the carrier loaded with rhBMP-2 (300 µg), and dental implant fixtures were inserted. The animals were kept alive for a further 4 weeks. Bone formation was examined using plane radiographs, micro-CT, and the histology of undecalcified specimens. The group treated with the rhBMP-2-loaded carrier composite showed a significantly higher percentage bone volume and a greater trabecular thickness for the newly formed bone in the tooth defect areas when compared to the group treated with the carrier alone. The rhBMP-2 group had a significantly higher osseointegration, a larger percentage bone volume, greater trabecular thickness in the newly formed bone in tooth defect areas, a larger newly formed bone fraction in the fixture pitch, and a greater number of newly formed trabecular bones when compared to the other groups. We confirmed that the rhBMP-2-loaded carrier composite promotes new bone formation after tooth extraction and strengthens osseointegration of dental fixtures by improving the degree of osseointegration around the dental implant fixture.

Long-term surgical outcomes of cervical myelopathy with athetoid cerebral palsy.

PURPOSE: To understand the long-term surgical outcomes and prognostic factors for the operative treatment of cervical myelopathy (CM) in patients with athetoid cerebral palsy (ACP). METHODS: We retrospectively reviewed 24 patients with ACP who underwent surgery for CM at our hospital between March 2002 and June 2008. All patients had more than 5 years follow-up. Anterior fusion (11 patients), posterior fusion (1 patient), or combined anterior and posterior (AP) fusion (7 patients) and C1-2 fusion (5 patients) surgeries were performed. Surgical outcomes (average follow-up 102 months), as assessed using modified JOA (mJOA) scores, the Neck Disability Index (NDI), and a visual analog scale (VAS) were compared between the preoperative and postoperative states. RESULTS: Preoperatvie cervical kyphosis decreased mJOA scores significantly. Long-term follow-up clinical outcomes demonstrated that 10 patients showed favorable (excellent and good) outcomes and 11 patients had non-favorable (fair and worse) outcomes. According to the mJOA scores, patients showed postoperative improvement (7.10-10.45). NDI decreased from 68.46 to 31.66. A second operation was done in seven cases due to instrument failure, progressive kyphotic deformities and adjacent segment degeneration. A preoperative botulinum toxin injection significantly decreased (p < 0.05) the incidence of a second operation. CONCLUSIONS: Patients with ACP have high incidence of instrument failure. Strong surgical fixation, bone fusion and perioperative immobilizations using botulinum toxin injection should be carefully planned preoperatively.

Toloese Generates Nitric Oxide through Natural Radiation of Far Infrared Rays, Reducing Serum Glucose, Cholesterol, and Triglycerides.

Toloese, a bed composition, is formulated with a combination of minerals of various wavelengths by utilizing a specific ratio and particle size. A maturation mixing technique is used without additional compression processes, resulting in the natural formation of numerous fine pores in the bed structure. At 40 °C, far infrared radiation in the range of 5-20 µm is emitted with a 0.916 radiant ratio, and the measured emitted radiant energy is 3.69 × 102 W/m2·µm. This study aimed to investigate the influence of far infrared radiation emitted from a Toloese bed on endogenous nitric oxide production. Clinical trials were conducted with 20 healthy adults aged 20 years. Blood samples were collected before and after Toloese bed usage for 1 h daily for 3 weeks. Nitric oxide levels in the saliva and blood of men and women significant increased after they used the Toloese bed for 1 h. Additionally, sweating sharply increased in the upper and lower body regions after Toloese bed usage. No hematological changes or adverse effects were observed, but blood glucose, cholesterol, and triglycerides decreased after Toloese bed usage compared with those before Toloese bed usage. These findings demonstrated that far infrared radiation emitted by the Toloese bed induced endogenous nitric oxide production and contributed to significant reductions in blood glucose, cholesterol, and triglyceride levels.

Retrospective analysis on prognosis of oral cancer patients according to surgical approaches for effective cancer ablation: swing approach versus visor approach.

BACKGROUND: For the surgical treatment of oral cancer, it is sometimes necessary to expand intraoral access within the oral cavity. The "swing approach" that involves lip splitting of the mandible and temporary mandibular osteotomy and the "visor approach" that does not split the lower lip and mandible are mainly used. This study analyzed postoperative outcomes such as complications, recurrence rate, and survival rate by these two approaches. The goal of this study is to evaluate the surgical outcomes of patients using these two approaches, to propose effective perioperative management for oral cancer surgery, and to compare the prognosis of oral cancer patients. MATERIALS AND METHODS: From 2005 to 2020, 29 patients who underwent surgery at the Department of Oral and Maxillofacial Surgery of Pusan National University Dental Hospital for oral cancer lesions occurred in the mandible, floor of mouth, and tongue were selected for the study. Based on the surgical approach used, a chart review was conducted on various prognostic clinical factors such as the patients' sex and age, primary site, TNM stage, histopathologic grade, recurrence and metastasis, postoperative survival rate, adjuvant chemo-radiation therapy, satisfaction with aesthetics/function/swallowing, length of hospital stay, tracheostomy and its duration, and neck dissection and its type. Statistical analysis was conducted using SPSS 25.0 (SPSS Inc., Chicago, IL) through Fisher's exact t-test. RESULT: There was no statistically significant difference between two groups in terms of clinical and pathological findings, such as survival rate, the need for adjuvant therapies, and the local recurrence rate. Although better outcomes were observed in terms of function, aesthetics, and postoperative complications in the group with visor approach, there was still no statistically significant difference between two groups. However, the duration of hospital stay was shorter in the visor approach group. CONCLUSION: There was no statistically significant difference in clinical prognostic factors between the swing approach and the visor approach. Therefore, when choosing between the two approaches for the ablation of oral cancer, it is considered to select the surgical priority approach that can be easy access based on the size and location of the lesion. The visor approach had advantages of aesthetics and healing period.

Distribution and pathogen prevalence of field-collected ticks from south-western Korea: a study from 2019 to 2022.

Hard ticks are known vectors of various pathogens, including the severe fever with thrombocytopenia syndrome virus, Rickettsia spp., Coxiella burnetii, Borrelia spp., Anaplasma phagocytophilum, and Ehrlichia spp. This study aims to investigate the distribution and prevalence of tick-borne pathogens in southwestern Korea from 2019 to 2022. A total of 13,280 ticks were collected during the study period, with H. longicornis accounting for 86.1% of the collected ticks. H. flava, I. nipponensis and A. testudinarium comprised 9.4%, 3.6%, and 0.8% of the ticks, respectively. Among 983 pools tested, Rickettsia spp. (216 pools, 1.6% MIR) were the most prevalent pathogens across all tick species, with R. japonica and R. monacensis frequently detected in I. nipponensis and Haemaphysalis spp., respectively. Borrelia spp. (28 pools, 0.2% MIR) were predominantly detected in I. nipponensis (27 pools, 13.8% MIR, P < 0.001). Co-infections, mainly involving Rickettsia monacensis and Borrelia afzelii, were detected in I. nipponensis. Notably, this study identified R. monacensis for the first time in A. testudinarium in South Korea. These findings offer valuable insights into the tick population and associated pathogens in the region, underscoring the importance of tick-borne disease surveillance and prevention measures.

Mithramycin A inhibits myeloid cell leukemia-1 to induce apoptosis in oral squamous cell carcinomas and tumor xenograft through activation of Bax and oligomerization.

In several human malignancies, overexpression of myeloid cell leukemia-1 (Mcl-1) confers resistance to induction of apoptosis; however, Mcl-1-mediated inhibition of apoptosis in oral squamous cell carcinoma (OSCC) is not fully understood and has been investigated in this study. The Mcl-1 promoter activators (TPA) and epidermal growth factor (EGF) enhanced neoplastic transformation of JB6 cells and this response was accompanied by enhanced expression of Mcl-1, and knockdown of Mcl-1 by RNA interference (RNAi) decreased JB6 cell transformation. In the same cell line, we also demonstrated that mithramycin A (Mith) decreased TPA-induced JB6 cell transformation and Mcl-1 expression. Mcl-1 was overexpressed in human oral tumors compared with normal oral mucosa and also in several OSCC cell lines including HN22 and HSC-4 cells. Treatment of these cells with Mith also decreased Mcl-1 expression and neoplastic cell transformation, and this was accompanied by induction of several markers of apoptosis. Knockdown of Mcl-1 by RNAi also induced apoptotic cell death. The downregulation of Mcl-1 by Mith and RNAi increased pro-apoptotic protein Bax, resulting in the Bax translocation into mitochondria and its oligomerization. Mith also suppressed tumor growth in vivo and induced apoptosis in tumor by also regulating expression of Mcl-1 and Bax proteins. These indicate a critical role for Mcl-1 in the growth and survival of OSCC and demonstrate that Mith may be a potential anticancer drug candidate for clinical treatment of OSCC.

Retrospective analysis of treatment outcomes for extranodal NK/T-cell lymphoma (ENKL), nasal type, stage I-IIE: single institute experience of combined modality treatment for early localized nasal extranodal NK/T-cell lymphoma (ENKL).

Extranodal natural killer/T-cell lymphoma (ENKL) is a very aggressive disease frequently involving the nasal cavity and upper aerodigestive tract. We retrospectively reviewed the treatment outcomes and treatment-associated complications of the patients with stage I-II early localized ENKL. A total of 24 patients were included. All patients were treated with combined chemoradiotherapy. Three, sixteen, and five patients were initially treated with radiation therapy, chemotherapy, and surgical procedures, respectively. Nine patients underwent hematopoietic stem cell transplantation (HSCT), and four patients administered immunotherapy with pegylated-interferon alpha. The mean observation time was 71.6 months (range, 29.7-183.6 months). Twenty patients achieved complete remission; thus, the overall response rate was 83.3 %. The 5-year overall survival (OS) and relapse-free survival (RFS) rates were 70.3 % and 62.2 %, respectively. In univariate analysis, HSCT was a significant prognostic indicator for OS and RFS. By combining HSCT, the 5-year OS and RFS rates were 100.0 % vs. 52.5 % (p = 0.018) and 88.9 % vs. 45.7 % (p = 0.045), respectively. Also, absence of B symptoms was a good prognostic factor for RFS, the 5-year RFS rate, 75.0 % vs. 25.0 % (p = 0.010), and B symptoms were significant for RFS in multivariate analysis (odds ratio = 7.4, confidence interval = 1.6~34.1, p = 0.011). However, a total of four cases of grade 3 toxicities were reported. Radiation dose range (≤4,500 vs. >4,500 cGy) was significantly correlated with late complications, as more severe complications occurred more frequently with a radiation dose >4,500 cGy (p = 0.026, in multivariate analysis). For more efficient treatment of ENKL, chemotherapy, HSCT, and/or immunotherapy can be combined with radiation therapy to prolong long-term survival and achieve good local control. Also, lower radiation dose could be administered to avoid severe late complications.