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Abstract We compared survival outcomes of high-dose concomitant boost radiotherapy (HDCBRT) and conventional dose radiotherapy (CRT) for newly diagnosed glioblastoma (GB). Patients treated with intensity-modulated radiation therapy for newly diagnosed GB were included. In HDCBRT, specific targets received 69, 60, and 51 Gy in 30 fractions, while 60 Gy in 30 fractions was administered with a standard radiotherapy method in CRT. Overall survival (OS) and progression-free survival (PFS) were compared using the Log-rank test, followed by multivariate Cox analysis. The inverse probability of treatment weighting (IPTW) method was also applied to each analysis. Among 102 eligible patients, 45 received HDCBRT and 57 received CRT. With a median follow-up of 16 months, the median survival times of OS and PFS were 21 and 9 months, respectively. No significant differences were observed in OS or PFS in the Kaplan–Meier analyses. In the multivariate analysis, HDCBRT correlated with improved OS (hazard ratio, 0.49; 95% confidence interval, 0.27–0.90; P = 0.021), and this result remained consistent after IPTW adjustments (P = 0.028). Conversely, dose suppression due to the proximity of normal tissues and IMRT field correlated with worse OS and PFS (P = 0.008 and 0.049, respectively). A prospective study with a stricter protocol is warranted to validate the efficacy of HDCBRT for GB.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a pandemic. Paucity of information concerning the virus and therapeutic interventions have made SARS-CoV-2 infection a genuine threat to global public health. Therefore, there is a growing need for understanding the molecular mechanism of SARS-CoV-2 infection at cellular level. To address this, we undertook a systems biology approach by analyzing publicly available RNA-seq datasets of SARS-CoV-2 infection of different cells and compared with other lung pathogenic infections. Our study identified several key genes and pathways uniquely associated with SARS-CoV-2 infection. Genes such as interleukin (IL)-6, CXCL8, CCL20, CXCL1 and CXCL3 were upregulated, which in particular regulate the cytokine storm and IL-17 signaling pathway. Of note, SARS-CoV-2 infection strongly activated IL-17 signaling pathway compared with other respiratory viruses. Additionally, this transcriptomic signature was also analyzed to predict potential drug repurposing and small molecule inhibitors. In conclusion, our comprehensive data analysis identifies key molecular pathways to reveal underlying pathological etiology and potential therapeutic targets in SARS-CoV-2 infection.

Abstract Background The Fontan procedure has become the standard operation for patients with single ventricle physiology. Due to cardiac hypokinesis and high central venous pressure, laparoscopic approach, especially in hepatectomy, was considered as controversial after the Fontan procedure. We presented a case of hepatocellular carcinoma (HCC) that was successfully treated by pure laparoscopic hepatectomy with stable pneumoperitoneum after the Fontan procedure. Case presentation An 18-year-old man was referred to our hospital for examination of a hepatic tumor. The patient underwent the Fontan procedure for single ventricle physiology at 6 years of age. Abdominal contrast-enhanced computed tomography (CT) revealed a hypovascular mass in segment 2 and a hypervascular mass in segment 4 of the arterial phase, followed by a delayed washout. CT arteriography revealed that both masses showed hypervascular tumors, and CT during arterial portography showed that both were low-density masses. The patient’s general condition was good, and cardiac and respiratory functions were well maintained. Pure laparoscopic hepatectomy was safely performed by keeping the pneumoteritoneum pressure under 6–8 mmHg and monitoring central venous pressure (11–21 mmHg) and end-tidal carbon dioxide. The Pringle maneuver was applied during hepatic resection. The non-anatomical resections were completed without intraoperative complications. The patient was discharged on the 9th postoperative day without postoperative complications. Conclusions Our report suggests that treatment of HCC by pure laparoscopic hepatectomy after Fontan circulation can be safely performed in patients under sufficient circulatory management.

Here we aimed to establish a simple detection method for detecting circulating tumor cells (CTCs) in the blood sample of colorectal cancer (CRC) patients using poly(2-methoxyethyl acrylate) (PMEA)-coated plates. Adhesion test and spike test using CRC cell lines assured efficacy of PMEA coating. A total of 41 patients with pathological stage II–IV CRC were enrolled between January 2018 and September 2022. Blood samples were concentrated by centrifugation by the OncoQuick tube, and then incubated overnight on PMEA-coated chamber slides. The next day, cell culture and immunocytochemistry with anti-EpCAM antibody were performed. Adhesion tests revealed good attachment of CRCs to PMEA-coated plates. Spike tests indicated that ~75% of CRCs from a 10-mL blood sample were recovered on the slides. By cytological examination, CTCs were identified in 18/41 CRC cases (43.9%). In cell cultures, spheroid-like structures or tumor-cell clusters were found in 18/33 tested cases (54.5%). Overall, CTCs and/or growing circulating tumor cells were found in 23/41 CRC cases (56.0%). History of chemotherapy or radiation was significantly negatively correlated with CTC detection (p = 0.02). In summary, we successfully captured CTCs from CRC patients using the unique biomaterial PMEA. Cultured tumor cells will provide important and timely information regarding the molecular basis of CTCs.

Abstract Background Focal segmental glomerulosclerosis is characterized by partial (segmental) sclerotic lesions in some glomeruli (focal). Primary focal segmental glomerulosclerosis is generally considered resistant to steroid therapy. However, acromegaly is a disease that causes peculiar facial features, body types, and metabolic abnormalities due to the excessive secretion of growth hormone by a pituitary adenoma. Growth hormone has been reported to be involved in glomerular cell growth, mesangial proliferation, and glomerulosclerosis in the kidney. Case presentation We report a case of a Japanese patient with focal segmental glomerulosclerosis in whom decreased urinary protein was observed after surgical treatment for acromegaly. Conclusion The patient’s urinary protein improved as the concentration of growth hormone/insulin-like growth factor 1 decreased.

Abstract Background Elongated styloid process syndrome (Eagle’s syndrome) is the term given to the symptomatic elongation of the styloid process or the mineralization of the stylohyoid or stylomandibular ligament. The two commonly used approaches for the surgical treatment of this syndrome are the transcervical and transoral approaches. Both have their limitations and specific intraoperative risks. Here, we report the treatment of a patient with Eagle’s syndrome using the transoral approach in conjunction with piezoelectric surgery, surgical planning, and intraoperative navigation to reduce the risk of complications. Case presentation The elongated styloid process was resected in a 45-year-old Japanese man using a minimally invasive approach with an intraoperative navigation system. Preoperative preparation involved the use of a custom interocclusal splint to produce the mouth opening conditions required during surgery. Using the three-dimensional position of the navigation probe, the location of the elongated styloid process was identified. After confirmation of the resection spot via the transoral approach, the styloid process was dissected by piezoelectric surgery. Follow-up examination showed an uneventful recovery with no associated complications. Conclusion The resection of the styloid process using an intraoperative navigation system and a custom interocclusal splint during a transoral approach, together with a piezoelectric cutting device, is safe and effective for the treatment of Eagle’s syndrome.

Bone lid surgery is a valid method for maxillofacial surgery as it can avoid the large bone defects secondary to access osteotomies. A precise and careful osteotomy together with firm placement of the bone lid in its original position enables better bone healing. Computer-assisted intraoperative navigation has recently evolved to improve the precision and simplify this surgical procedure. However, the application of computerized navigation-assisted surgery to the mandible is complicated because of its mobility. Here we present the feasible modified application of bone lid surgery to mandibular lesions using an intraoperative navigation system.

Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In this study we analyzed SHH expression and the role played by SHH signaling in gingival carcinoma-induced jawbone destruction. From an analysis of surgically resected lower gingival squamous cell carcinoma mandible samples, we found that SHH was highly expressed in tumor cells that had invaded the bone matrix. On the other hand, the hedgehog receptor Patched and the signaling molecule Gli-2 were highly expressed in the osteoclasts and the progenitor cells. SHH stimulated osteoclast formation and pit formation in the presence of the receptor activator for nuclear factor-κB ligand (RANKL) in CD11b+ mouse bone marrow cells. SHH upregulated phosphorylation of ERK1/2 and p38 MAPK, NFATc1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K expression in RAW264.7 cells. Our results suggest that tumor-derived SHH stimulated the osteoclast formation and bone resorption in the tumor jawbone microenvironment.

OSTEOTRANS MX® (Takiron Co., Ltd., Osaka, Japan) is a bioactive resorbable maxillofacial osteosynthetic material composed of an unsintered hydroxyapatite/poly-l-lactide composite, and its effective osteoconductive capacity has been previously documented. However, the mechanical strength of this plate system is unclear. Thus, the aim of this in vitro study was to assess its tensile and shear strength and evaluate the biomechanical intensity of different osteosynthesis plate designs after sagittal split ramus osteotomy by simulating masticatory forces in a clinical setting. For tensile and shear strength analyses, three mechanical strength measurement samples were prepared by fixing unsintered hydroxyapatite/poly-l-lactide composed plates to polycarbonate skeletal models. Regarding biomechanical loading evaluation, 12 mandibular replicas were used and divided into four groups for sagittal split ramus osteotomy fixation. Each sample was secured in a jig and subjected to vertical load on the first molar teeth. Regarding shear strength, the novel-shaped unsintered hydroxyapatite/poly-l-lactide plate had significantly high intensity. Upon biomechanical loading evaluation, this plate system also displayed significantly high stability in addition to bioactivity, with no observed plate fracture. Thus, we have clearly demonstrated the efficacy of this plate system using an in vitro model of bilateral sagittal split ramus osteotomy of the mandible.

Several biological studies have indicated that hedgehog signaling plays an important role in osteoblast proliferation and differentiation, and sonic hedgehog (SHH) expression is positively correlated with phosphorylated focal adhesion kinase (FAK) Tyr(397). However, the relationship between them and their role in the process of normal fracture repair has not been clarified yet. Immunohistochemical analysis revealed that SHH and pFAK Tyr(397) were expressed in bone marrow cells and that pFAK Tyr(397) was also detected in ALP-positive osteoblasts near the TRAP-positive osteoclasts in the fracture site in the ribs of mice on day 5 after fracture. SHH and pFAK Tyr(397) were detectable in osteoblasts near the hypertrophic chondrocytes on day 14. In vitro analysis showed that SHH up-regulated the expression of FAK mRNA and pFAK Tyr(397) time dependently in osteoblastic MC3T3-E1 cells. Functional analysis revealed that 5 lentivirus encoding short hairpin FAK RNAs (shFAK)-infected MC3T3-E1 cell groups displayed a round morphology and decreased proliferation, adhesion, migration, and differentiation. SHH stimulated the proliferation and differentiation of MC3T3-E1 cells, but had no effect on the shFAK-infected cells. SHH also stimulated osteoclast formation in a co-culture system containing MC3T3-E1 and murine CD11b(+) bone marrow cells, but did not affect the shFAK-infected MC3T3-E1 co-culture group. These data suggest that SHH signaling was activated in osteoblasts at the dynamic remodeling site of a bone fracture and regulated their proliferation and differentiation, as well as osteoclast formation, via FAK signaling.