circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models.

Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.

Effect of ultrasound assisted H2O2/Vc treatment on the hyperbranched Lignosus rhinocerotis polysaccharide: Structures, hydrophobic microdomains, and antitumor activity.

The effect of ultrasonic intensity (28.14, 70.35, and 112.56 W/cm2) on Lignosus rhinocerotis polysaccharide (LRP) degraded by ultrasound assisted H2O2/Vc system (U-H/V) was investigated. U-H/V broke the molecular chain of LRP and improved the conformational flexibility, decreasing the molecular weight, intrinsic viscosity ([η]) and particle size. The functional groups and hyperbranched structure of LRP were almost stable after U-H/V treatment, however, the triple helix structure of LRP was partially disrupted. With increasing ultrasonic intensity, the critical aggregation concentration increased from 0.59 mg/mL to 1.57 mg/mL, and the hydrophobic microdomains reduced. Furthermore, the LRP treated with U-H/V significantly inhibited HepG2 cell proliferation by inducing apoptosis. The increase in antitumor activity of LRP was closely associated with the reduction of molecular weight, [η], particle size and hydrophobic microdomains. These results revealed that U-H/V treatment facilitates the degradation of LRP and provides a better insight into the structure-antitumor activity relationship of LRP.

Dehydrozaluzanin C- derivative protects septic mice by alleviating over-activated inflammatory response and promoting the phagocytosis of macrophages.

Host-directed therapy (HDT) is a new adjuvant strategy that interfere with host cell factors that are required by a pathogen for replication or persistence. In this study, we assessed the effect of dehydrozaluzanin C-derivative (DHZD), a modified compound from dehydrozaluzanin C (DHZC), as a potential HDT agent for severe infection. LPS-induced septic mouse model and Carbapenem resistant Klebsiella pneumoniae (CRKP) infection mouse model was used for testing in vivo. RAW264.7 cells, mouse primary macrophages, and DCs were used for in vitro experiments. Dexamethasone (DXM) was used as a positive control agent. DHZD ameliorated tissue damage (lung, kidney, and liver) and excessive inflammatory response induced by LPS or CRKP infection in mice. Also, DHZD improved the hypothermic symptoms of acute peritonitis induced by CRKP, inhibited heat-killed CRKP (HK-CRKP)-induced inflammatory response in macrophages, and upregulated the proportions of phagocytic cell types in lungs. In vitro data suggested that DHZD decreases LPS-stimulated expression of IL-6, TNF-α and MCP-1 via PI3K/Akt/p70S6K signaling pathway in macrophages. Interestingly, the combined treatment group of DXM and DHZD had a higher survival rate and lower level of IL-6 than those of the DXM-treated group; the combination of DHZD and DXM played a synergistic role in decreasing IL-6 secretion in sera. Moreover, the phagocytic receptor CD36 was increased by DHZD in macrophages, which was accompanied by increased bacterial phagocytosis in a clathrin- and actin-dependent manner. This data suggests that DHZD may be a potential drug candidate for treating bacterial infections.

Characterization of the distinct immune microenvironments between hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

As two major types of primary liver cancers, the tumor immune microenvironment (TIME) of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have been well studied separately. However, a systemic assessment of the similarities and differences between the TIME of HCC and ICC is still lacking. In this study, we pictured a landscape of combined TIME of HCC and ICC by sequencing and integrating 41 single-cell RNA-seq samples from four different tissue types of both malignancies. We found that T cells in HCC tumors generally exhibit higher levels of immunosuppression and exhaustion than those in ICC tumors. Myeloid cells in HCC and ICC tumors also exhibit distinct phenotypes and may serve as a key factor driving the differences between their TIMEs. Besides, we identified a cluster of EGR1+ macrophages specifically enriched in HCC tumors. Together, our study provides new insights into cellular composition, states and interactions in the TIMEs of HCC and ICC, which could pave the way for the development of future therapeutic targets for liver cancers.

MiR-17-5p-engineered sEVs Encapsulated in GelMA Hydrogel Facilitated Diabetic Wound Healing by Targeting PTEN and p21.

Delayed wound healing is a major complication of diabetes, and is associated with impaired cellular functions. Current treatments are unsatisfactory. Based on the previous reports on microRNA expression in small extracellular vesicles (sEVs), miR-17-5p-engineered sEVs (sEVs17-OE) and encapsulated them in gelatin methacryloyl (GelMA) hydrogel for diabetic wounds treatment are fabricated. SEVs17-OE are successfully fabricated with a 16-fold increase in miR-17-5p expression. SEVs17-OE inhibited senescence and promoted the proliferation, migration, and tube formation of high glucose-induced human umbilical vein endothelial cells (HG-HUVECs). Additionally, sEVs17-OE also performs a promotive effect on high glucose-induced human dermal fibroblasts (HG-HDFs). Mechanism analysis showed the expressions of p21 and phosphatase and tensin homolog (PTEN), as the target genes of miR-17-5p, are downregulated significantly by sEVs17-OE. Accordingly, the downstream genes and pathways of p21 and PTEN, are activated. Next, sEVs17-OE are loaded in GelMA hydrogel to fabricate a novel bioactive wound dressing and to evaluate their effects on diabetic wound healing. Gel-sEVs17-OE effectively accelerated wound healing by promoting angiogenesis and collagen deposition. The cellular mechanism may be associated with local cell proliferation. Therefore, a novel bioactive wound dressing by loading sEVs17-OE in GelMA hydrogel, offering an option for chronic wound management is successfully fabricated.

Multi-scale structural disruption induced by radio frequency air cold plasma accelerates enzymatic hydrolysis/ hydroxypropylation of tapioca starch.

This study investigated the effects of radio frequency air cold plasma (RFACP) pretreatment on the multi-scale structures, physicochemical properties, enzymatic hydrolysis, and hydroxypropylation of tapioca starch. The results showed that cold plasma (CP) made starch granules rough on the surface and disrupted long- and short-range ordered structures, reducing relative crystallinity from 43.8 % to 37.4 % and R1047/1022 value from 0.992 to 0.934. Meanwhile, the starch molecules were depolymerized and oxidized by CP, reducing weight-average molecular weight from 9.64 × 107 to 2.17 × 107 g/mol, while increasing carbonyl and carboxyl groups by up to 118 % and 53 %. Additionally, CP-treated starches exhibited higher solubility and swelling power, along with lower gelatinization enthalpy. Short-time CP pretreatment (10 min) promoted the hydroxypropylation of starch and increased the molar substitution (0.081-0.112). Also, CP pretreatment accelerated enzymatic hydrolysis of starch, as indicated by the increase in hydrolysis rate (1.846 × 10-3-2.033 × 10-3 min-1) and degree of hydrolysis (51.45 % - 59.92 %). Overall, the multi-scale structural disruption induced by CP treatment facilitated the accessibility of enzymes/chemical reagents into starch granules and glucan chains. This study suggested that RFACP could be used for starch pretreatment to increase production efficiency in modified starch production, as well as in brewing and fermentation industries.

UBDP1 pseudogene and UBD network competitively bind miR­6072 to promote glioma progression.

Increasing evidence suggests that pseudogenes play crucial roles in various cancers, yet their functions and regulatory mechanisms in glioma pathogenesis remain enigmatic. In the present study, a novel pseudogene was identified, UBDP1, which is significantly upregulated in glioblastoma and positively correlated with the expression of its parent gene, UBD. Additionally, high levels of these paired genes are linked with a poor prognosis for patients. In the present study, clinical samples were collected followed by various analyses including microarray for long non­coding RNAs, reverse transcription­quantitative PCR, fluorescence in situ hybridization and western blotting. Cell lines were authenticated and cultured then subjected to various assays for proliferation, migration, and invasion to investigate the molecular mechanisms. Bioinformatic tools identified miRNA targets, and luciferase reporter assays validated these interactions. A tumor xenograft model in mice was used for in vivo studies. In vitro and in vivo studies have demonstrated that UBDP1, localized in the cytoplasm, functions as a tumor­promoting factor influencing cell proliferation, migration, invasion and tumor growth. Mechanistic investigations have indicated that UBDP1 exerts its oncogenic effects by decoying miR­6072 from UBD mRNA, thus forming a competitive endogenous RNA network, which results in the enhanced oncogenic activity of UBD. The present findings offered new insights into the role of pseudogenes in glioma progression, suggesting that targeting the UBDP1/miR­6072/UBD network may serve as a potential therapeutic strategy for glioma patients.

MiR-141-3p-Functionalized Exosomes Loaded in Dissolvable Microneedle Arrays for Hypertrophic Scar Treatment.

Hypertrophic scar (HS) is a common fibroproliferative disease caused by abnormal wound healing after deep skin injury. However, the existing approaches have unsatisfactory therapeutic effects, which promote the exploration of newer and more effective strategies. MiRNA-modified functional exosomes delivered by dissolvable microneedle arrays (DMNAs) are expected to provide new hope for HS treatment. In this study, a miRNA, miR-141-3p, which is downregulated in skin scar tissues and in hypertrophic scar fibroblasts (HSFs), is identified. MiR-141-3p mimics inhibit the proliferation, migration, and myofibroblast transdifferentiation of HSFs in vitro by targeting TGF-ß2 to suppress the TGF-ß2/Smad pathway. Subsequently, the engineered exosomes encapsulating miR-141-3p (miR-141-3pOE -Exos) are isolated from adipose-derived mesenchymal stem cells transfected with Lv-miR-141-3p. MiR-141-3pOE -Exos show the same inhibitive effects as miR-141-3p mimics on the pathological behaviors of HSFs in vitro. The DMNAs for sustained release of miR-141-3pOE -Exos are further fabricated in vivo. MiR-141OE -Exos@DMNAs effectively decrease the thickness of HS and improve fibroblast distribution and collagen fiber arrangement, and downregulate the expression of α-SMA, COL-1, FN, TGF-ß2, and p-Smad2/3 in the HS tissue. Overall, a promising, effective, and convenient exosome@DMNA-based miRNA delivery strategy for HS treatment is provided.

Naringin alleviates pneumonia caused by Klebsiella pneumoniae infection by suppressing NLRP3 inflammasome.

Klebsiella pneumoniae (Kpn) is an important pathogen of hospital-acquired pneumonia, which can lead to sepsis and death in severe cases. In this study, we simulated pneumonia induced by Kpn infection in mice to investigate the therapeutic effect of naringin (NAR) on bacterial-induced lung inflammation. Mice infected with Kpn exhibited increases in white blood cells (WBC) and neutrophils in the peripheral blood and pathological severe injury of the lungs. This injury was manifested by increased expression of the inflammatory cytokines interleukin (IL)- 18, IL-1ß, tumor necrosis factor-α (TNF-α) and IL-6, and elevated the expression of NLRP3 protein. NAR treatment could decrease the protein expression of NLRP3, alleviate lung inflammation, and reduce lung injury in mice caused by Kpn. Meanwhile, molecular docking results suggest NAR could bind to NLRP3 and Surface Plasmon Resonance (SPR) analyses also confirm this result. In vitro trials, we found that pretreated with NAR not only inhibited nuclear translocation of nuclear factor (NF)-κB protein P65 but also attenuated the protein interaction of NLRP3, caspase-1 and ASC and inhibited the assembly of NLRP3 inflammasome in mice AMs. Additionally, NAR could reduce intracellular potassium (K+) efflux, inhibiting NLRP3 inflammasome activation. These results indicated that NAR could protect against Kpn-induced pneumonia by inhibiting the overactivation of the NLRP3 inflammasome signaling pathway. The results of this study confirm the efficacy of NAR in treating bacterial pneumonia, refine the mechanism of action of NAR, and provide a theoretical basis for the research and development of NAR as an anti-inflammatory adjuvant.

Middle Ear Meningioma With Recurrence Secretory Otitis Media.

Middle ear meningiomas (MEMs) are rare tumors that can present with nonspecific symptoms, posing challenges in diagnosis and management. This case report focuses on a middle-aged female patient who was misdiagnosed with secretory otitis media for 5 years. However, further evaluation through computed tomography imaging and subsequent pathologic biopsy revealed the presence of a MEM. The patient underwent surgical and gamma knife resection of the tumor and follow-up examination after 1 year showed no signs of recurrence. This case report highlights the importance of considering meningiomas in the differential diagnosis of middle ear pathologies and the need for careful preoperative planning for optimal outcomes. Overall, this case demonstrates that correct diagnosis and appropriate treatment can lead to successful management of MEMs.

Therapeutic Effect and Safety Evaluation of Naringin on Klebsiella pneumoniae in Mice.

Critically ill patients with Corona Virus Disease 2019 (COVID-19) often develop secondary bacterial infections that pose a significant threat to patient life safety, making the development of drugs to prevent bacterial infections in the lungs critical to clinical care. Naringin (NAR) is one of the significant natural flavonoids rich in Pummelo Peel (Hua Ju Hong), with anti-inflammatory, antimicrobial, and antioxidant activities, and is commonly used in treating respiratory tract infectious diseases. In this study, the in vitro and in vivo findings revealed that, after Klebsiella pneumoniae (Kpn) infection, NAR inhibited overactivation of the nuclear factor kappa-B(NF-κB) signaling pathway in alveolar macrophages of mice, reduced neutrophil (NEs) recruitment, and lowered the induced production of proinflammatory markers, such as Interleukin-6(IL-6) and tumor necrosis factor α(TNF-α). Thus, it suppressed excessive immune responses in the lungs, as well as attenuated the induced pulmonary fibrosis and inflammatory infiltrates. These results suggest that NAR has a preventive effect against Kpn in mice. In addition, the study evaluated NAR's potential toxicity, demonstrating that NAR is safe at effective doses. These results suggested that NAR effectively reduces excessive inflammatory damage in the lungs induced by Kpn and enhances the body's ability to clear bacteria. Therefore, NAR may be an effective and safe healthcare drug for preventing and caring for bacterial pneumonia.

The cellular uptake of Cordyceps sinensis exopolysaccharide­selenium nanoparticles and their induced apoptosis of HepG2 cells via mitochondria- and death receptor-mediated pathways.

This wok investigated the effects of Cordyceps sinensis exopolysaccharide­selenium nanoparticles (EPS-SeNPs), EPS-Se-1, EPS-Se-2, EPS-Se-3, and EPS-Se-4) with particle sizes (79-124 nm) and Se contents (20.11-40.80 µg/mg) on endocytosis and antitumor activity against human hepatocellular carcinoma (HepG2) cells and revealed the apoptosis-related mechanisms. EPS-SeNPs inhibited HepG2 cells proliferation in a dose and Se content-dependent manner by disrupting cell membrane and mitochondrial integrity, promoting reactive oxygen species production. EPS-SeNPs were endocytosed by HepG2 cells through a clathrin-mediated pathway and followed the quasi-first-order kinetics model, indicating physical adsorption played a dominant role in cellular uptake behavior of EPS-SeNPs. Notably, EPS-Se-3 with the lowest particle size (79 nm) showed the highest antitumor activity and the strongest ability to promote cell apoptosis. Western blotting results revealed that EPS-Se-3 increased expressions of Bax, Cytochrome c, cleaved caspase-9, cleaved caspase-3, Fas, p53, and cleaved caspase-8, while decreased the expressions of Bcl-2 and PARP, as contrast to that of control. Overall, EPS-SeNPs induced cell apoptosis through intrinsic mitochondria-mediated and extrinsic death receptor-mediated pathways.

Inhibition of CARM1 suppresses proliferation of multiple myeloma cells through activation of p53 signaling pathway.

BACKGROUND: Multiple myeloma (MM) is a malignant proliferative disease of plasma cells, the incidence of which is increasing every year and remains incurable. The enzyme co-activator-associated arginine methyltransferase 1 (CARM1) is highly expressed in a variety of cancers, such as Hodgkin's lymphoma and acute myeloid leukemia, and CARM1 is closely associated with tumor cell proliferation. However, the role of CARM1 in MM has not been elucidated. METHODS AND RESULTS: In this study, we found that CARM1 is overexpressed in MM and closely associated with poor prognosis in MM. CCK-8 and colony formation assays showed that the proliferation of MM cell lines was downregulated when CARM1 expression was knockdown by specific shRNA. Knockdown of CARM1 reduced the proportion of MM cell lines in the S phase and increased the proportion in G0/G1 phase. RNA-seq analysis of the CARM1-KD cell line revealed that it was closely associated with apoptosis and activated the p53 pathway. CCK-8 and apoptosis results showed that CARM1 knockdown made MM cells more sensitive to standard-of-care drugs. CONCLUSION: This study provides an experimental basis for elucidating the pathogenesis of multiple myeloma and searching for potential therapeutic targets.

Isolation, structural features, rheological properties and bioactivities of polysaccharides from Lignosus rhinocerotis: A review.

L. rhinocerotis, an edible and medicinal mushroom, has long been utilized as folk medicine and nutritional food in Southeast Asia and southern China. Polysaccharides are the main bioactive substances of L. rhinocerotis sclerotia, and they have attracted extensive attention of researchers both at home and abroad. In the past few decades, various methods have been applied to extract polysaccharides from L. rhinocerotis (LRPs) and the structural features of LRPs are closely related to the used methods of extraction and purification. Many studies have confirmed that LRPs possess various remarkable bioactivities, including immunomodulatory, prebiotic, antioxidant, anti-inflammatory and anti-tumor activities and intestinal mucosa protective effect. As a natural polysaccharide, LRP has the potential to be a drug and functional material. This paper systematically reviews the recent studies on structural characteristics, modification, rheological properties and bioactivities of LRPs, and provides a theoretical basis for an in-depth study of the structure-activity relationship, and utilization of LRPs as therapeutic agents and functional foods. Additionally, the further research and development of LRPs are also prospected.

Different oil-modified cross-linked starches: In vitro digestibility and its relationship with their structural and rheological characteristics.

This study investigated the structure, rheological behaviors and in vitro digestibility of oil-modified cross-linked starches (Oil-CTS). Gelatinized Oil-CTS were hard to be digested due to its intact granule shapes and the presence of surface-oil, which acted as physical barriers that inhibited the diffusion and penetration of enzymes to starch. Besides, the less amylose content in Oil-CTS (23.19-26.96%) than other starches (26.84-29.20%) contributed to its low digestibility because amylose with less α-1,6 linkages was more easily attacked by amyloglucosidase than amylopectin. Moreover, heat treatment during oil could shorten the amylopectin chain length and destroy the ordered structures, thus increasing enzymatic hydrolysis on starch. Pearson correlation analysis indicated rheological parameters were not significantly correlated with digestion parameters (p > 0.05). Overall, despite the damage caused by heat to molecular structures, physical barrier effect caused by surface-oil layers and integrity of swollen granules was the most critical contributor to the low digestibility of Oil-CTS.

MiR146a-loaded engineered exosomes released from silk fibroin patch promote diabetic wound healing by targeting IRAK1.

Unhealable diabetic wounds need to be addressed with the help of newer, more efficacious strategies. Exosomes combined with biomaterials for sustained delivery of therapeutic agents are expected to bring new hope for chronic wound treatment. Here, the engineered exosomes modified for efficiently loading miR146a and attaching to silk fibroin patch (SFP) were demonstrated to promote diabetic wound healing. Silk fibroin binding peptide (SFBP) was screened through phage display, and SFBP-Gluc-MS2 (SGM) and pac-miR146a-pac fusion protein were constructed. The designed exosomes (SGM-Exos, miR146a-Exos, and SGM-miR146a-Exos) were isolated from the engineered placental mesenchymal stem cells (PMSCs) transduced with SGM or/and pac-miR146a-pac protein. Gluc signals indicated SGM-Exo@SFP markedly increased the binding rate and the stability of SGM-Exo. Moreover, the loading efficiency of miR146a in SGM-miR146a-Exos was ten-fold higher than that in miR146a-Exos. Superior to untreated, SGM-miR146a-Exo-only treated, and SFP-only treated groups, SGM-miR146a-Exo@SFP drived wound healing associated with less inflammation, collagen deposition, and neovascularization. The transcriptomics analysis suggested anti-inflammatory and regenerative effects with SGM-miR146a-Exo@SFP treatment. Here, we show efficient exosome@biomaterial-based miRNA delivery systems for regenerative medicine and tissue engineering.

Competitive electrochemical sensing for cancer cell evaluation based on thionine-interlinked signal probes.

The development of effective methods for tracking cancer cells is of significant importance in the early diagnosis and treatment of tumor diseases. Compared with the developed techniques, the electrochemical assay has shown considerable potential for monitoring glycan expression on the cell surface using nondestructive means. However, the application expansion of the electrochemical strategy is strongly impeded owing to its dependence on electroactive species. In this study, a competitive electrochemical strategy was reported for monitoring cancer cells based on mannose (a typical glycan) as a clinical biomarker. Herein, functionalized carbon nanotubes were used to load the thiomannosyl dimer, and thionine-interlinking signal probes were designed for competitive recognition. After effective competition between cancer cells and the anchored mannose, a decreased current was obtained as the cell concentration increased. Under optimal conditions, the proposed biosensor exhibited attractive performance for cancer cell analysis with a detection limit as low as 20 cells per mL for QGY-7701 and 35 cells per mL for QGY-7703, facilitating great promise for the sensitive detection of cancer cells and thus showing potential applications in cancer diagnosis.

Effect of oil-modified crosslinked starch as a new fat replacer on gel properties, water distribution, and microstructures of pork meat batter.

This work investigated the effects of oil-modified crosslinked starch (Oil-CTS) as a fat replacer on the gel properties, water distribution, microstructures, and fatty acid composition of pork meat batter. Results showed that the replacement of pork back fat by Oil-CTS could improve the gel performance in terms of rheological property, texture, and water-holding capacity (WHC), and reduce the water mobility of pork meat gels, which caused by the formation of a more ordered and denser protein network structure. Additionally, when the fat was replaced by Oil-CTS partially or totally (25-100 %), the total fat content in pork meat gels decreased by 16.5-82 % and the saturated fatty acids (SFAs) content decreased from 5.87 g/100 g in untreated sample to 1.17-4.88 g/100 g in starch-replacing-fat samples, indicating Oil-CTS could be used as a fat replacer to prepare the low-fat meat products.

Myosin head as the main off-odors binding region: Key binding residues and conformational changes in the binding process.

This study aims to elucidate the dynamic binding characteristics between off-odors (hexanal, 1-octen-3-ol, nonanal) and myosin at cold storage (277 K) and oral temperatures (310 K) through spatial-temporal molecular dynamics (MD) simulation. Conformational analysis indicated that binding with off-odors could not significantly change the myosin secondary structure, and the myosin/(off-odors) structure became a stable and compact state in the later binding stages. Myosin head was the primary binding region with hydrophobic interactions as the dominant force rather than hydrogen bonds (average bond number 202.62 vs 55.20). Furthermore, the myosin/(off-odors) had larger binding energy at 310 than 277 K, and the myosin-nonanal showed the highest binding strength of 4050.93 kJ/mol at 310 K. The binding sites were observed to be concentrated in the 180-249, 350-410, 800-950 amino acid regions of myosin head, especially, Lys185, Tyr347, Leu901. These results provide accurate linkages between off-odors and myosin, laying a theoretical foundation for deodorization of fish products.

Diffuse-type Tenosynovial Giant Cell Tumor Invading the Temporal Bone: Three Cases.

Diffuse-type tenosynovial giant cell tumor (D-TSGCT) is a destructive benign tumor-like proliferative disease that occurs in synovial tissue characterized by villous nodular hyperplasia of joints, tendon sheaths, and synovium. D-TSGCT invading the temporal bone originating from the temporomandibular joint (TMJ) is very rare. Here, we report 3 cases of temporal bone D-TSGCT originating from the TMJ. The tumors in the three cases were originating from the TMJ and further invading the middle ear, the carotid foramen or the temporal lobe respectively. The second patient clearly involved the carotid foramen. The third patient clearly affected the temporal lobe. Lesions were completely removed in 3 cases, and all 3 patients were followed up for 30, 20, and 7 months, and none had recurrence. There are very few reports describing such cases. Although this report is not representative of most scenarios, there is still a potential that it provides a relatively reliable surgical idea for similar cases.