Synergistic effects of ischemic preconditioning and immediate post-conditioning in the protection against ischemia/reperfusion injury in rabbit submandibular glands.

Submandibular gland autotransplantation is an effective approach for treating severe keratoconjunctivitis sicca. However, ischemia/reperfusion (I/R) injury, which inevitably occurs during transplantation, is involved in the hypofunction and structural damage that occur early after transplantation. Therefore, it is critical to identify effective strategies to ameliorate I/R injury in submandibular glands. In this study, we investigated the ability of immediate post-conditioning combined with ischemic preconditioning to attenuate I/R injury. We observed that after I/R injury, the level of reactive oxygen species was increased, inflammatory response was strengthened, and severe apoptosis had occurred. In addition, the salivary flow rate was greatly decreased. However, the pathogenesis of I/R injury was significantly ameliorated by ischemia post-conditioning or ischemia preconditioning treatments. In addition, the combination of ischemia preconditioning and post-conditioning achieved synergistic protective effects against I/R injury compared with ischemia preconditioning or ischemia post-conditioning alone. The secretion function was restored in the combination group. Furthermore, the combination treatment involved the same mechanisms of ischemia preconditioning or ischemia post-conditioning, including suppression of the inflammatory reaction and neutrophil accumulation, attenuation of oxidation stress, and inhibition of apoptosis. In conclusion, the combination of ischemia preconditioning and ischemia post-conditioning treatment is a simple and effective approach for treating I/R injury in submandibular glands.

Microvascular Submandibular Gland Transplantation for Severe Keratoconjunctivitis Sicca: A Single-Institution Experience of 61 Grafts.

PURPOSE: Keratoconjunctivitis sicca (KCS) is a relatively common disease that results in discomfort, tear film instability, visual impairment, and ocular surface damage. Artificial tear substitutes may be suitable for the treatment of mild KCS, but no effective treatment currently exists for severe KCS. Therefore, this study evaluated the effectiveness of autologous microvascular submandibular gland transplantation in the treatment of severe KCS. PATIENTS AND METHODS: A total of 61 eyes (56 patients) with severe KCS were treated with autologous submandibular gland transplantation from June 2002 to June 2017. The cephalic vein or the great saphenous vein was applied to solve the problem of unmatched veins. RESULTS: In 53 cases (53 of 56, 94.6%), 58 glands (58 of 61, 95.1%) were transplanted successfully. The mean Schirmer I test value improved from 0.78 ± 0.84 mm preoperatively to 18.83 ± 5.72 mm in the stable period after transplantation. Epiphora (14 of 58, 24.14%) was the most common complication of this procedure. Other postoperative complications included venous thrombosis (6 of 61, 9.84%), local infection (2 of 58, 3.45%), xerostomia (2 of 53, 3.77%), duct fistula (1 of 58, 1.72%), sialolithiasis (1 of 58, 1.72%), and ranula (1 of 58, 1.72%). CONCLUSIONS: Autologous microvascular submandibular gland transplantation is a credible and effective solution for severe KCS.

Reconstruction of Tongue Defects With the Contralateral Nasolabial Island Flap.

PURPOSE: Reconstruction of tongue defects after cancer resection is challenging for reconstructive surgeons. Conventional local flaps are usually compromised in patients with suspected ipsilateral neck metastasis. To extend the application of the nasolabial flap, especially in circumstances in which a free flap is unavailable, the contralateral nasolabial island flap was used, with favorable outcomes. PATIENTS AND METHODS: Seven patients presenting with tongue carcinoma underwent surgical resection and neck dissection. Tongue defects were simultaneously reconstructed using a contralateral nasolabial island flap. Clinical outcomes, including locoregional recurrence and distant metastasis, were recorded. Subjective functional outcomes were investigated using the University of Washington Quality of Life Questionnaire. RESULTS: All flaps survived without partial or complete necrosis. All patients survived without locoregional recurrence or distant metastasis during follow-up (6 months to 2 years). Functional outcomes were satisfactory, especially swallowing and speech functions. Donor-site morbidity was minimal and the scars were inconspicuously hidden in the nasolabial fold. CONCLUSIONS: The contralateral nasolabial island flap is technically feasible and can be an excellent option for tongue reconstruction without compromising oncologic safety.

Current concepts in odontohypophosphatasia form of hypophosphatasia and report of two cases.

BACKGROUND: Hypophosphatasia is a rare inherited disease derived from mutations in tissue non-specific alkaline phosphatase genes, with typical oral symptoms including short root anomaly and dysplasia of dentin or cementum. CASE PRESENTATION: Two young female patients presented with short root anomaly with a history of premature loss of deciduous and/or permanent teeth. The laboratory and imaging investigations were performed. One case was diagnosed as odontohypophosphatasia concurrent with hyperthyroidism, the other was odontohypophosphatasia concurrent with multiple radicular cysts. CONCLUSION: This report presents two cases of odontohypophosphatasia, a rare disease which is difficult to be diagnosed, and highlights that the history of premature loss of deciduous and/or permanent teeth, oral manifestation and laboratory tests are crucial for clinical diagnosis.

Reinnervated nerves contribute to the secretion function and regeneration of denervated submandibular glands in rabbits.

This study aimed to investigate the contribution of redistributed nerves in the secretory function and regeneration of a denervated submandibular gland (SMG). The postganglionic parasympathetic and sympathetic denervated SMGs of rabbits were wrapped in polyester or acellular dermal matrices to block nerve regeneration either partially or completely. Submandibular glands were removed 4, 8, 16, and 24 wk after the operation and examined histologically. Furthermore, the aquaporin-5 (AQP5), muscarinic-3 (M3), and ß1-adrenergic receptors were evaluated by immunofluorescence and western blot analysis. After denervation, salivary flow was decreased and acinar cells were atrophic, and the expression levels of the M3, ß1-adrenergic, and AQP5 receptors were decreased. However, both impaired secretion function and atrophic parenchyma were gradually ameliorated with the growing redistribution of parasympathetic and sympathetic nerves. Apoptosis was markedly inhibited and expression of the M3, ß1-adrenergic, and AQP5 receptors was increased after reinnervation. In contrast, SMGs without reinnervated nerves maintained hyposecretion and atrophic parenchyma. In conclusion, reinnervated nerves in a rabbit's denervated SMG played an important role in the secretion function and regeneration of SMGs via up-regulation of the expression of neurotransmitter receptors and AQP5.

Suppression of tongue squamous cell carcinoma growth by inhibition of Jagged1 in vitro and in vivo.

BACKGROUND: The changes in Notch signaling are closely related to the occurrence and development of many cancers. We have investigated Notch signaling receptor and its ligand expressions in TSCC cell lines, tissues and its significance. We clarified Notch signaling pathway in TSCC and its mechanism. We regulated Notch signaling pathway of tumor cells, thereby inhibiting tumor cell proliferation and differentiation. METHODS: We detected Jagged1 protein and mRNA expression levels in specimens (tongue cancer and adjacent tissues) from 74 patients with tongue cancer and in TSCC cell line. The Jagged1-targeted lentiviral vector RNAi system was constructed, and its suppressive effects on the proliferation and invasion of tongue carcinoma cells in in vivo and ex vivo were determined. RESULTS: Jagged1 was expressed in tongue squamous cell cancer tissues and cell line, but there were differences in its expression. Jagged1 was knocked down and the tumor growth was inhibited accompanying cell cycle changes. Animal studies also showed that the tumor growth was inhibited. CONCLUSIONS: Jagged1 may be involved in the differentiation and proliferation of tongue cancer. Targeting Jagged1 RNA interference lentiviral vector can effectively lower Jagged1 mRNA and protein expression levels of Tca8113 cells, thereby preventing the proliferation of TSCC cells. Jagged1 is expected to be a promising new target for curing tongue cancer. In-depth study of the interaction between Jagged1 and other molecules of Notch signaling pathway in the process of carcinogenesis has important theoretical guidance and clinical significance in revealing the mechanism of Jagged1 and its application in the therapy for tongue cancer.

Inhibition of autophagy enhances cisplatin cytotoxicity in human adenoid cystic carcinoma cells of salivary glands.

BACKGROUND: The relationship between autophagy and chemotherapy in cancer has been studied a lot recent years. However, there is currently no study on the role of autophagy in chemotherapy of adenoid cystic carcinoma (ACC) of human salivary glands. We hypothesized that autophagy plays a protective role for human salivary gland ACC cells during chemotherapy, diminishes the effect of treatment, and ultimately results in poor sensitivity to chemotherapy. MATERIALS AND METHODS: After inhibition of autophagy by 5 mM 3-methyladenine (3MA), 20 µM Chloroquine (CQ), or Beclin-1 shRNA, we examined the sensitivity of human salivary gland ACC cells to different concentrations of cis-diamminedichloroplatinum (CDDP) using MTT assay. Also, levels of autophagy in ACC cells treated by CDDP were assessed by western blot, GFP-LC3 fluorescence and transmission electron microscopy (TEM). RESULTS: Inhibition of autophagy induced by 3MA, CQ, or Beclin-1 shRNA could all enhance human salivary gland ACC cell death treated by CDDP. And, levels of autophagy in these cells showed a significant increase after treated by CDDP. CONCLUSION: Autophagy played a protective role for human salivary gland ACC cells during CDDP chemotherapy. Inhibition of autophagy in these cells could enhance cisplatin cytotoxicity-effects. These findings indicate a novel and promising way to reduce chemotherapy resistance and improve treatment outcome in human salivary gland ACC.

Mandibular reconstruction assisted by preoperative simulation and accurate transferring templates: preliminary report of clinical application.

PURPOSE: This study investigated the application of a computer-aided design and manufacturing technique of defining tumor resection, fibula cutting, and positioning by surgical templates in mandibular reconstructive surgery. MATERIALS AND METHODS: Four patients who required mandibulectomy and simultaneous reconstruction were enrolled in this study. Preoperative surgical simulation was performed. The surgical templates that defined tumor resection, fibula cutting, and positioning were designed and fabricated. RESULTS: The surgeries were performed to the preoperative plan. All flaps survived. Superimposition of the postoperative image and the preoperative plan showed a satisfactory surgical accuracy. CONCLUSIONS: This method of defining tumor resection, fibula cutting, and positioning by surgical templates was accurate enough for mandibular reconstructive surgery.

High expression of the autophagy gene Beclin-1 is associated with favorable prognosis for salivary gland adenoid cystic carcinoma.

BACKGROUND: Although autophagy is universally involved in tumorigenesis and tumor progression, the roles of autophagy and autophagy-regulating genes in salivary gland adenoid cystic carcinoma (ACC) remain unknown. In this study, we investigated the expression of the autophagy-regulating genes Beclin-1, death-associated protein kinase-1, ultraviolet radiation resistance-associated gene, and phosphatase and tensin homolog in salivary gland ACC samples. METHODS: Immunohistochemistry and real-time polymerase chain reaction were used to analyze the expression of these genes in 89 ACC samples and normal salivary gland tissue samples. The relationship of their expression with clinicopathological features was analyzed. RESULTS: The data showed significantly lower expression of these genes in the tumor samples than in normal salivary gland tissue samples. Furthermore, Beclin-1 expression was significantly correlated with histological pattern of ACC (P<0.05), and high expression of ultraviolet radiation resistance-associated gene was associated with distant metastasis (P<0.05). Most importantly, univariate and multivariate survival analyses suggested that Beclin-1 protein and mRNA expression in cancer cells were independent prognostic indicators for ACC. CONCLUSION: Our results suggest that autophagy-regulating genes may participate in the pathogenesis of salivary gland ACC. Further research will be required to gain a better understanding of autophagy in ACC.

Mandible reconstruction assisted by preoperative simulation and transferring templates: cadaveric study of accuracy.

PURPOSE: In this study we tried to define tumor resection, fibula cutting, and positioning by surgical templates to perform the mandible reconstruction surgery according to the preoperative simulation. The accuracy was evaluated through cadaveric surgery. MATERIALS AND METHODS: Five cadaveric mandibles and fibulas were obtained. Preoperative surgical simulation was performed. Surgical templates that defined tumor resection, fibula cutting, and positioning were designed and fabricated. Translation, angular deviation, and rotation of bone grafts, as well as translation of condyles, were measured. RESULTS: The reconstructed mandibles showed high similarity to the surgical planning. The mean translation, angular deviation, and rotation of fibula segments of the reconstructed mandibles were 1.35 ± 0.86 mm, 3.36° ± 1.86°, and 8.13° ± 5.35°, respectively. In the mandible remnants, the translation of condyles was measured, with a mean of 1.39 ± 0.66 mm. CONCLUSIONS: Our method of defining the tumor resection, fibula cutting, and positioning by surgical templates was accurate enough for mandible reconstruction surgery.

PDGF-BB exhibited therapeutic effects on rat model of bisphosphonate-related osteonecrosis of the jaw by enhancing angiogenesis and osteogenesis.

The mechanism and effective treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) are still uncertain. Our previous study revealed that zoledronate (ZOL) preferentially inhibited osteoclasts formation and platelet-derived growth factor-BB (PDGF-BB) secretion, causing suppression of angiogenesis and osteogenesis in vitro. The present study aimed to elucidate whether PDGF-BB had therapeutic effects on rat model of BRONJ by enhancing angiogenesis and angiogenesis. Firstly, rat model of BRONJ was established by ZOL and dexamethasone administration, followed by teeth extraction. The occurrence of BRONJ was confirmed and detected dead bone formation by maxillae examination, micro-CT scan and HE staining (10/10). Compared to control rats (0/10), both angiogenesis and mature bone formation were suppressed in BRONJ-like rats, evidenced by enzyme-linked immunosorbent assay (ELISA) for VEGF (P < 0.01), immunohistochemistry of CD31 (P < 0.05) and OCN (P < 0.01). Moreover, in the early stage of bone healing, the number of preosteoclasts (P < 0.001) and PDGF-BB secretion (P < 0.05) were significantly decreased in bisphosphonates-treated rats, along with the declined numbers of microvessels (P < 0.05) and osteoblasts (P < 0.05). In vitro study, CCK8 assay, alizarin red S staining and western blot assay showed that mandible-derived bone marrow mesenchymal stem cells (BMMSCs) in BRONJ-like rats presented suppressed functions of proliferation, osteogenesis and angiogenesis. Interestingly, recombinant PDGF-BB was able to rescue the impaired functions of BMMSCs derived from BRONJ-like rats at more than 10 ng/ml. Then fibrin sealant with or without recombinant PDGF-BB were tamped into the socket after debridement in BRONJ rats. After 8 weeks, fibrin sealant containing PDGF-BB showed significant therapeutic effects on BRONJ-like rats (bone healing: 8/10 vs 3/10, P < 0.05) with enhancing microvessels and mature bone formation. Our study suggested that the inhibition of angiogenesis and osteogenesis, the potential mechanisms of BRONJ, might partly result from suppression of PDGF-BB secretion in the early stage of bone healing. PDGF-BB local treatment after debridement might avail the healing of BRONJ by increasing angiogenesis and osteogenesis.

Detection of Notch signaling molecules in cemento-ossifying fibroma of the jaws.

BACKGROUND: The aim of this study was to evaluate the roles of Notch signaling in the oncogenesis and cytodifferentiation of cemento-ossifying fibroma, the expressions of Notch receptors and ligands were detected in COF and normal jaw bones. MATERIALS AND METHODS: The expressions of Notch1, Notch3, Jagged1, and Jagged2 were detected by reverse transcriptase polymerase chain reaction and immunohistochemistry respectively in 16 cases of normal bone tissues and 12 cases of COF of the jaws. RESULTS: The mRNAs expressions of Notch1, Notch3, Jagged1, and Jagged2 were detected in all specimens. The expression levels of mRNAs in COF were higher than those in normal bones. In COF, Notch proteins staining were showed extensively distribution in fibroblasts and osteoblasts. In normal bone tissue, Notch proteins were expressed in osteoblasts, whereas proteins staining were weaker than those in COF, but no detection in fibroblast-like bone marrow stroma cells. The expressions of Notch receptors and ligands were not detected in cementum-like products or bone matrices. CONCLUSION: Our data suggest that Notch signaling may participate in controlling cell differentiation and proliferation in normal bone and COF of the jaws. Notch signaling disorder may be a molecular incident in COF occurrence and development.

Sialoendoscopic secondary intervention after failure of open sialolithectomy.

PURPOSE: Traditionally, sialoadenectomy was always indicated when open sialolithectomy failed. The aim of the present study was to investigate the role of sialoendoscopy as the secondary intervention after failure of open sialolithectomy. PATIENTS AND METHODS: A consecutive series of 15 patients with obstructive salivary gland disease with failure of open sialolithectomy were prospectively recruited for our study. All these patients underwent sialoendoscopy under local anesthesia. The reasons for the failure of open sialolithectomy were analyzed, and secondary interventions were performed using sialoendoscopy. RESULTS: Failure of open sialolithectomy resulted from 4 main causes. Small stones could not be found after the duct was incised (n = 3); the stones were pushed posteriorly during open surgery (n = 4); the stones located in the anterior part of the duct were removed, but the hilar stones were left untouched (n = 5); and radiolucent stones were missed (n = 3). All the patients were treated successfully by sialoendoscopy. No symptoms or signs of recurrence developed during a median follow-up period of 16 months. CONCLUSIONS: Sialoendoscopy can be recommended as an effective secondary intervention after failure of open sialolithectomy.

Sialoendoscopically assisted open sialolithectomy for removal of large submandibular hilar calculi.

PURPOSE: The management of large hilar calculi is a technically challenging issue during sialoendoscopic surgery. The aim of the present study was to evaluate the clinical efficacy of sialoendoscopically assisted open sialolithectomy for the removal of large submandibular hilar calculi to avoid sialoadenectomy. PATIENTS AND METHODS: The present study was undertaken among patients with sialolithiasis scheduled for sialoendoscopic surgery from August 2005 to October 2008. When we failed to remove large submandibular hilar stones intraductally, we performed sialoendoscopically assisted open sialolithectomy. The clinical characteristics, pre- and intraoperative data, and outcomes were documented in a prospective fashion. RESULTS: Of 78 consecutive patients with submandibular sialolithiasis, 18 were treated with sialoendoscopically assisted open sialolithectomy immediately after failure of intraductal removal of calculi by sialoendoscopy. For 17 patients, large hilar sialoliths were successfully removed using this surgical technique. The surgery failed in 1 patient with multiple sialoliths, and the procedure was converted to open sialoadenectomy. Temporary numbness of the tongue for 1 week postoperatively was documented in 3 patients. The patients were followed up for a median period of 18 months without any symptoms or signs of recurrence. CONCLUSION: Our results suggest that sialoendoscopically assisted open sialolithectomy is an effective and safe surgical technique to remove large submandibular hilar calculi.

Promoted Bone Regeneration by 3D-Printed Porous Scaffolds with the Synergy of a Nanotopological Morphology and Amino Modification.

Three-dimensional (3D)-printed scaffolds have great advantages for bone repair, and the combination of physical and chemical modifications of the surface can improve deficient biological properties to promote bone regeneration. In this study, a nanotopological morphology and an amino group were introduced into scaffold surfaces in sequence by alkaline solution and amination, respectively. The surface properties and the ability for osteogenic induction were investigated. The nanotopological morphology of the surface slightly enhanced the hydrophilic property of the material, while amination obviously increased the hydrophilicity of the surface. The aminated surface improved cell adhesion and proliferation, while the nanotopological morphology was able to facilitate the spread of stem cells, pseudopod extension, and osteogenic differentiation by changing the cell skeleton. The study confirmed that a nanotopological morphology and an amino group can play synergistic roles in improving the osteogenic efficiency and hydrophilicity, which was also confirmed in vivo by showing that effective surface modification of polylactic acid scaffolds enhanced high-quality bone formation, thus demonstrating great potential for clinical applications. The results indicate that scaffolds with the synergy of a nanotopological morphology and amino modification improve the osteogenic induction ability of scaffolds.

Polydopamine-Assisted Anchor of Chitosan onto Porous Composite Scaffolds for Accelerating Bone Regeneration.

Surface function has an importance for the bioactivity of porous polymeric scaffolds. The goal of the present study is to immobilize highly bioactive chitosan (CS) onto the surface of porous composite scaffolds to accelerate bone regeneration. Porous poly(ε-caprolactone) (PCL)/bioactive glass (BG) composite scaffolds with strong anchor of CS were fabricated via mussel-inspired polydopamine (PDA) coating as a bridging layer. In vitro cell culture showed that firm immobilization of CS onto the composite scaffolds significantly enhanced protein adsorption, cell adhesion, and osteogenic differentiation compared to CS-decorated scaffolds via physical adsorption. In vivo assessments demonstrated that covalent immobilization of CS onto the surface of scaffolds obviously promoted cranial bone regeneration in comparison with the counterparts with physical adsorption of CS. The proposed method offers a feasible and effective means to fabricate artificial bioactive scaffolds for bone tissue engineering application.

Neoadjuvant chemotherapy of cisplatin and fluorouracil regimen in head and neck squamous cell carcinoma: a meta-analysis.

BACKGROUND: The benefit of neoadjuvant chemotherapy in the management of head and neck squamous cell carcinomas (HNSCC) still remains controversial. The aim of this meta-analysis is to evaluate the role of the neoadjuvant chemotherapy with the cisplatin and fluororacil (PF) regimen in enhancing the overall survival of and decreasing locoregional relapse and distant metastasis in HNSCC patients. METHODS: Medline and manual searches were performed to identify all published randomized controlled trials (RCTs) investigating the efficacy of the neoadjuvant chemotherapy with the PF regimen. Outcomes assessed by meta-analysis included locoregional relapse, distant metastasis, and overall survival. The odds ratio was the principle measurement of effect, which was calculated as the treatment group (chemotherapy plus locoregional treatment) versus the control group (locoregional treatment alone) and was presented as a point estimate with 95% confidence intervals (CI). RESULTS: Eight RCTs were adopted for analysis. The meta-analysis showed that the odds ratio for the locoregional relapse was 0.92 (0.70 - 1.22, 95% CI), which was not statistically significant. The odds ratios for distant metastasis and overall survival were 0.47 (0.33 - 0.68, 95% CI) and 1.28 (1.01 - 1.62, 95% CI) respectively, which were both statistically significant. CONCLUSIONS: Neoadjuvant chemotherapy with the PF regimen in HNSCC patients has no effect on locoregional relapse. However, it shows a small but significant benefit in reducing distant metastasis and improving the overall survival.

Marsupialization of mandibular cystic ameloblastoma: Retrospective study of 7 years.

BACKGROUND: This retrospective study investigated the reduction rate and speed of shrinkage after marsupialization in mandibular cystic ameloblastoma and clarified whether marsupialization is appropriate for unicystic ameloblastoma and multicystic ameloblastoma. METHODS: Sixty-three patients with mandibular cystic ameloblastoma were initially treated with marsupialization. Premarsupialization and postmarsupialization panoramic radiographs were reviewed for reduction rate and speed of shrinkage, and then were evaluated with age, sex, tumor location, and tumor type. RESULTS: The overall recurrence rate was 4.5% (2/44). The average reduction rate after marsupialization was 65.6%. No significant difference was found between unicystic ameloblastoma and multicystic ameloblastoma in reduction rate. The speed of shrinkage of unicystic ameloblastoma was significantly faster than that of multicystic ameloblastoma (P < .05). Similarly, patients with multicystic ameloblastoma had longer marsupialization periods than those with unicystic ameloblastoma (P < .05). CONCLUSION: Marsupialization is effective in reducing tumor size for both unicystic ameloblastoma and multicystic ameloblastoma. Marsupialization plus second-stage curettage is recommended as the primary treatment for mandibular cystic ameloblastoma.

Risk factors and prognosis for salivary gland adenoid cystic carcinoma in southern china: A 25-year retrospective study.

Adenoid cystic carcinoma (ACC) is characterized by slow growth, frequent local recurrences, and high incidence of distant metastasis (DM). The aim of this study was to evaluate predictive factors for local-regional (LR) recurrence, DM, and survival in ACC.A retrospective review of the medical records for patients with salivary glands ACC from 1990 to 2015 was performed. The clinical parameters were assessed to identify correlations with the development of LR recurrence, DM, and survival of these patients.Among 228 patients who underwent surgery as definitive treatment, 210 (92.1%) were followed up in the study. DM was detected in 64 (30.5%) patients, LR recurrence was detected in 58 (27.6%) patients. The estimated 5, 10, and 15-year overall survival rates were 84.7%, 70.8%, and 34.0%, respectively. Multivariate analysis revealed that the presence of lymphovascular invasion and a high T classification were very strong adverse factors, which independently influenced LR recurrence, DM, and survival of ACC patients. Positive/close margin and N+ status were independent risk factors for DM and LR recurrence, respectively. Survival of ACC patents was also affected by tumor location.Presence of lymphovascular invasion and a high T classification were very strong adverse factors and independent predictors for ACC patients' prognosis, which influenced LR control, DM control, and survival.