Objective: To investigate the efficacy and drug related adverse reactions of sorafenib and sunitinib as first-line tyrosine-kinase inhibitors (TKIs) for patients with metastatic renal cell carcinoma (mRCC) and analyze the clinical prognostic factor for survival. Methods: The data of 271 patients with metastatic renal cell carcinoma who had complete clinicopathological data were retrospectively analyzed, including 174 cases in sorafenib group and 97 cases in sunitinib group, to access patients' overall survival (OS) and progression-free survival (PFS). Prognostic values of all characteristics were determined by using univariate and multivariate Cox regression models. Results: The objective response rates (ORR) of the sorafenib and sunitinib groups were 14.9% and 19.6%, respectively, and the disease control rates (DCR) were 85.1% and 88.6%, respectively. No significant difference was found between the sorafenib and sunitinib group in ORR (P=0.325) or DCR (P=0.408). The most common grade 3 to 4 adverse events in the sorafenib group were hand-foot syndrome (6.7%), diarrhea (2.3%), and rash (2.3%). The most common grade 3 to 4 adverse events in the sunitinib group were neutropenia (6.2%), hand-foot syndrome (6.2%), and thrombocytopenia (4.6%). During the follow-up, 97 cases death occurred and 81 cases disease progression occurred in sorafenib group. The median PFS was 12 months (95% CI: 9-15 months), and the median OS was 25 months (95% CI: 21-29 months) in sorafenib group. While 74 cases death occurred and 40 cases disease progression occurred in sunitinib group, the median PFS was 12 months (95% CI: 10-12 months) and the median OS was 23 months (95% CI: 20-32 months) in sunitinib group. No significant difference was found between the sorafenib and the sunitinib group in PFS (P=0.771) or OS (P=0.548). Multivariate analysis showed Fuhrman grades (HR=1.358, 95%CI: 1.004-1.835), number of metastatic sites (HR=1.550, 95%CI: 1.143-2.101) and MSKCC risk grade (Intermediate risk group: HR=1.621, 95%CI: 1.117-2.232; Poor risk group: HR=2.890, 95%CI: 1.942-4.298) were independent prognostic factors for PFS. Fuhrman grades (HR=2.135, 95%CI: 1.533-2.974), number of metastatic sites (HR=1.774, 95%CI: 1.279-2.461) and MSKCC risk grade (Intermediate risk group: HR=1.415, 95%CI: 1.002-1.998; Poor risk group: HR=3.161, 95%CI: 2.065-4.838) were independent prognostic factors for OS. Conclusions: The results of this study indicate that sorafenib and sunitinib are both effective as the first-line TKIs for mRCC patients and sorafenib has comparable efficacy to sunitinib. But they have differences in the incidence of adverse effects. Fuhrman grades, number of metastatic sites and MSKCC risk grade are independent prognostic factors for mRCC patients.目的：评价索拉非尼和舒尼替尼作为一线酪氨酸激酶抑制剂(TKI)治疗转移性肾癌的疗效和安全性，并探讨患者预后的影响因素。 方法：回顾性分析271例临床病理资料完整的转移性肾癌患者的资料，其中索拉非尼组174例，舒尼替尼组97例，评价索拉非尼组和舒尼替尼组的疗效和不良反应。采单因素和多因素Cox比例风险模型分析预后影响因素。 结果：索拉非尼组和舒尼替尼组的客观反应率分别为14.9%和19.6 %，疾病控制率分别为85.1%和88.6%，两组差异均无统计学意义(P值分别为0.325和0.408)。索拉非尼组最常见的3～4级不良反应为手足综合征(6.7%)、腹泻(2.3%)和皮疹(2.3%)。舒尼替尼组最常见的3～4级不良反应为中性粒细胞下降(6.2%)、手足综合征(6.2%)和血小板下降(4.6%)。随访期间，索拉非尼组死亡97例，疾病进展81例。中位无进展生存时间(PFS)为12个月(95%CI：9～15个月)，中位总生存时间(OS)为25个月(95%CI：21～29个月)。舒尼替尼组死亡74例，疾病进展40例。中位PFS为12个月(95%CI：10～12个月)，中位OS为23个月(95%CI：20～32个月)。两组PFS和OS差异均无统计学意义(P值分别为0.771和0.548)。多因素分析显示，Fuhrman分级(HR＝1.358，95%CI：1.004～1.835)、转移器官数(HR＝1.550，95%CI：1.143～2.101)及(纪念斯隆－凯特林癌症中心MSKCC)危险分级(中危组：HR ＝1.621，95%CI：1.117～2.232；高危组：HR＝2.890，95%CI：1.942～4.298)是转移性肾癌患者PFS的独立影响因素。Fuhrman分级(HR＝2.135，95%CI：1.533～2.974)、转移器官数(HR＝1.774，95%CI：1.279～2.461)及MSKCC危险分级(中危组：HR＝1.415，95%CI：1.002～1.998；高危组：HR＝3.161，95%CI：2.065～4.838)是转移性肾癌患者OS的独立影响因素。 结论：索拉非尼与舒尼替尼作为一线TKI药物治疗转移性肾癌疗效显著，两者疗效无明显差异，药物相关不反应分布有所不同。Fuhrman分级、转移器官数和MSKCC评分是转移性肾癌患者预后的独立影响因素。.
Objective To assess the effects of different application sequences of neodymium-doped yttrium aluminum garnet(Nd∶YAG)laser and the desensitizing toothpaste containing stannous fluoride on dentinal tubule occlusion.Methods Twelve intact third molars freshly extracted from human were selected and prepared into dentin slices with a thickness of 0.8 mm.Each dentin slice was subdivided into four small slices,three of which were etched with 6% citric acid and randomly assigned to the following three groups(n=12):(1)control group:no treatment;(2)Nd∶YAG+toothbrushing(TB)group:first irradiated with Nd∶YAG laser and then brushed with desensitizing toothpaste;(3)TB+Nd∶YAG group:first brushed with desensitizing toothpaste and then irradiated with Nd∶YAG laser.The Nd∶YAG laser irradiation were carried out at 1 W,15 pulses/s,and the pulse width of 150 μs for 10 s(for a total of 6 cycles).After the above treatment,the 12 dentin slices from the Nd∶YAG+TB and TB+Nd∶YAG groups were randomly assigned to four subgroups(n=3)and subjected to acid etching in the Coca-Cola solution for 0,5,10,and 15 min.A scanning electron microscope was used to observe and photograph the dentin slices in each group,and eight single-blinded examiners scored the slices according to uniform criteria.The analysis of variance was carried out to compared the scores between groups.Results Before acid etching,the dentin tubule occlusion scores of the Nd∶YAG+TB and TB+Nd∶YAG groups were(4.83±0.09) scores and(3.85±0.66) scores,respectively,which had no significant difference between each other(P=0.0590)and were higher than that[(0.10±0.07)scores]of the control group(both P<0.0001).The dentin tubule occlusion scores of the Nd∶YAG+TB group after acid etching for 5,10,and 15 min were(4.33±0.60)scores,(4.27±0.24)scores,and(3.63±0.07)scores,respectively,which were not significantly different from those[(4.04±0.10)scores,(3.76±0.59)scores,and(3.17±0.29)scores,respectively]of the TB+Nd∶YAG group(all P>0.05).In the Nd∶YAG+TB subgroup,the dentin tubule occlusion score after acid etching for 15 min was significantly lower than that before acid etching(P=0.0011).In the TB+Nd∶YAG group,there was no statistically significant difference in the score between before and after acid etching(P>0.05).Conclusions Nd∶YAG laser irradiation with appropriate parameters combined with the use of desensitizing toothpaste could produce an excellent occluding effect on dentinal tubules regardless of the sequence.However,brushing with desensitizing toothpaste followed by Nd∶YAG laser irradiation produced more consistent dentin sealing after acid etching.目的 评估掺钕钇铝石榴石(Nd∶YAG)激光和含有氟化亚锡系统的脱敏牙膏不同应用顺序对牙本质小管封闭效果的影响。方法 选择12颗完整的新鲜拔除的人第三磨牙制备成0.8 mm厚牙本质片,将每个牙本质片再分为4小片,取其中3小片,用6%的柠檬酸进行腐蚀,随机分配至以下3组(n=12):(1)对照组:无处理;(2)Nd∶YAG激光+牙膏(TB)组:先用Nd∶YAG激光照射,后用脱敏牙膏刷牙;(3)TB+Nd∶YAG组:先用脱敏牙膏刷牙,后用Nd∶YAG激光照射。Nd∶YAG激光照射参数均为:1 W,15脉冲/s,脉冲宽度150 μs,照射10 s,6个循环。经上述处理后,将Nd∶YAG+TB组和TB+Nd∶YAG组的12个牙本质片随机分配到4个亚组(n=3),分别在可口可乐液中接受酸蚀0、5、10、15 min。采用扫描电子显微镜观察各组牙本质片并拍片,由8名单盲检查员根据统一标准给出评分,采用方差分析对各组评分进行比较。结果 酸蚀前,Nd∶YAG+TB组和TB+Nd∶YAG组的牙本质小管封闭评分分别为(4.83±0.09)分和(3.85±0.66)分,均明显高于对照组的(0.10±0.07)分(P均<0.0001),Nd∶YAG+TB组与TB+Nd∶YAG组差异无统计学意义(P=0.0590)。Nd∶YAG+TB组酸蚀5、10、15 min牙本质小管封闭评分分别为(4.33±0.60)、(4.27±0.24)、(3.63±0.07)分,与TB+Nd∶YAG组的(4.04±0.10)、(3.76±0.59)、(3.17±0.29)分差异均无统计学意义(P均>0.05)。在Nd∶YAG+TB亚组中,酸蚀15 min牙本质小管封闭评分明显低于酸蚀前(P=0.0011)。在TB+Nd∶YAG组中,酸蚀前后牙本质小管封闭评分间差异无统计学意义(P>0.05)。结论 适当参数的Nd∶YAG激光照射结合使用脱敏牙膏,不论先后顺序,均可以产生良好的牙本质小管封闭效果,但是先用脱敏牙膏刷牙后用Nd∶YAG 激光照射组在酸蚀后的牙本质封闭效果更稳定。.
Introduction: Hemorrhagic transformation (HT) is a severe but frequent complication of acute ischemic stroke (AIS). This study aimed to evaluate the relationship between serum LDH levels and HT. Methods: We retrospectively included 542 AIS patients with HT and 1091 age and gender-matched patients without HT. Demographic and clinical data were obtained from medical records, and blood samples were obtained within 24 hours after admission. The characteristics of groups were compared. With the receiver operating characteristic curve (ROC) analysis, we assessed the discriminating capacity of LDH levels in predicting HT in patients with AIS. The logistic regression model was used to determine the connection between LDH and HT. Results: The HT group had considerably higher LDH levels than the non-HT group [263.0 (216.0-323.3) U/L vs. 178.0 (162.0-195.0) U/L, P < 0.001]. We also observed that the levels of LDH in the parenchymal hemorrhage (PH) subgroup were significantly higher than those in the hemorrhagic infarction (HI) subgroup [281.0 (230.0-340.0) U/L vs. 258.0 (209.0-311.0) U/L, P < 0.001]. The area under the ROC curve (AUC) of LDH was 0.890 (95% CI 0.874-0.905, P < 0.001). Besides, logistic regression revealed that high LDH levels (LDH > 215 U/L) showed a higher risk of HT [odds ratio (OR) = 10.958, 95% confidence level (CI) 7.964-15.078, P < 0.001]. Conclusion: High LDH levels were linked with an increased risk of HT in AIS patients. Practical measures should be considered in patients with increased LDH levels (LDH > 215 U/L).
The outer hair cell (OHC) of the mammalian cochlea is the nexus of the active processes giving rise to the nonlinear, biologically vulnerable, acoustic response. We present a model for the behavior of the OHC in view of its mechanical and electrical properties, and the external loading of the cell. Because of the low-pass electrical membrane impedance and rate dependent processes, there is a continuing debate on the mechanism of the amplification process at high frequencies. We will focus on the electrical-to-mechanical energy conversion at the cellular level, and show how we must consider the external mechanical loading of the cell to interpret the power transfer. In addition, we show that simple models can be used to fit in vitro data from experiments, but subtle model changes in the parameters change the predictions of power deposition by the OHCs.
Background: Preoperatively staging extracapsular extension (ECE) of renal cell carcinoma (RCC) is crucial for determining appropriate treatment option. Artificial intelligence (AI) can provide a great potential to reduce human-derived variability and improve accuracy.Purpose: The aim of this study is to develop and test an expert-AI interactive networks (KtSNet+) for staging RCCs with contrast-enhanced CT (CECT).Materials and Methods: A total of 1,024 patients with clear cell RCC underwent kidney CECT and nephrectomy were retrospectively collected in two centers. The KtSNet+ was trained using a hybrid Resnet3d networks mounted with experts-guided attention map in 611 training datasets, with the aim to emulate the acumen of experts for ECE staging. KtSNet+ was evaluated independently in 413 datasets by comparing diagnostic performance to a 'black-box' network without attention guidance (KtSNet), experienced-based Likert score by three radiologists, and a radiomics model using XGBoost (RadXGBoost), respectively.Results: Likert score by three readers has high heterogeneity (inter-reader agreements, 34.9% to 47.8%) in staging ECE. In internal validation, KtSNet+ has higher (p < 0.01) AUC (0.78) than KtSNet (0.68), RadXGBoost (0.53), tumor diameter (0.63), volume (0.61), and Likert score by three readers (0.53 to 0.70). In external validation, KtSNet+ (0.88) is comparable (p 0.05) to KtSNet (0.85), tumor diameter (0.86) and volume (0.87), while is superior to RadXGBoost (0.61; p < 0.01). In a pooled Meta-regression analysis, KtSNet+ outperforms all the other methods regarding higher diagnostic odds ratio and higher summary AUC for ECE staging.ConclusionThe proposed KtSNet+, allowing for human-AI interaction and interpretation, offers a promising alternative to human experts for ECE staging using contrast-enhanced CT.Funding Information: This work was supported by the Key research and development program of Jiangsu Province; contract grant number: BE2017756 (to Y.D.Z.).Declaration of Interests: All authors declare that they have no Conflict of Interests. Ethics Approval Statement: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee of the First Affiliated Hospital of Nanjing Medical University and with the 1964 Helsinki Declaration and its later amendments; ethics grant number:2022-SR-408. Informed consent was waived by the institutional research committee.
Background: Colonic neuroendocrine carcinomas (co-NECs) are heterogeneous and aggressive, especially with regard to metastasis. Whether co-NECs on the right and left sides of the colon have different characteristics from colon adenocarcinoma is unknown. Methods: The co-NEC patients were selected from the 2010–2017 Surveillance, Epidemiology, and End Results Program (SEER) database. The right and left sides of the colon were separated by the splenic flexure. Coarsened exact matching (CEM) was performed to adjust for relevant factors before regression models were constructed. Results: A total of 669 pathologically diagnosed co-NEC patients with sufficient baseline data were identified from the SEER database. A total of 80.72% of the patients had co-NEC that originated from the right side of the colon, and their mean overall survival (mOS) was similar to that of the patients with left-sided co-NECs (right versus left: 22.30 m versus 22.55 m). A total of 44.84% of the patients were diagnosed with liver metastasis (46.68% right side versus 37.98% left side). In patients with liver metastasis, those with right-sided co-NECs had better survival than those with left-sided co-NECs (mOS right versus left: 15.37 m versus 9.62 m; adjusted hazard ratio (HR) = 0.69, 95% confidence interval (CI): 0.49–0.98, p = 0.035). To further investigate the survival benefits of primary site resection, we separated the patients who had liver metastasis according to the primary site and performed CEM to balance the groups (no patients underwent liver metastasis resection or intervention). The results suggested that primary surgery could benefit patients with both left- and right-sided co-NECs (adjusted HR = 0.50, 95% CI: 0.33–0.77, p = 0.001 on the right side; HR = 0.38, 95% CI: 0.16–0.89, p = 0.026 on the left side). Conclusions: Co-NECs frequently originate on the right side and commonly develop liver metastasis. Right-sided co-NECs are associated with better survival than left-sided co-NECs after liver metastasis has occurred. Primary site resection is associated with prolonged survival in co-NEC patients with liver metastasis, regardless of the side from which the co-NEC has originated.
A radicular groove is an anatomic malformation that usually initiates at the central fossa, extending along the root at varying lengths and depths and predisposes the involved tooth to a severe periodontal defect. Severe grooves that extend to the root apex often lead to complex combined periodontal-endodontic lesions. They are a serious challenge for doctors to diagnose and treat.In this report, we described a patient with a maxillary lateral incisor with a deep palatogingival groove with two roots, which led to complex combined periodontal-endodontic lesions. Suggested treatment modalities included curettage of the affected tissues, elimination of the groove by grinding and/or sealing with a variety of filling materials, and surgical procedures. In this case, a combination of endodontic therapy, intentional replantation, and root resection were used, which resulted in periodontal/periradicular healing after 12 mo.Intentional replantation and root resection offer a predictable procedure and should be considered a viable treatment modality for the management of palatogingival grooves, especially for two-rooted teeth.
Background/Aims: Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) is abnormally expressed in gastrointestinal (GI) malignancies. However, the correlation between SPARCL1 expression and the prognosis of patients remains unknown. Therefore, we performed a meta-analysis to investigate the potential value of SPARCL1 as a prognostic predictive marker for GI malignancies. Methods: The PubMed, Embase, EBSCO, CNKI, and Wanfang databases were systematically searched for studies examining SPARCL1 and clinicopathological features, including the prognoses of patients. Hazard ratios (HRs) and odds ratios (ORs) from individual studies were calculated and pooled using a random-effects or fix-effects model. Heterogeneity and publication bias analyses were performed. Results: Data from 8 studies, including a total of 2,356 patients, were summarized. The expression of SPARCL1 suggested a better prognosis (HR=0.57, 95% CI: 0.445-0.698, P=0.000) and was associated with clinicopathological features of GI malignancies, including distant metastasis (OR=0.44, 95% CI: 0.23-0.85, P=0.014), lymph node metastasis (OR=0.56, 95% CI: 0.39–0.81, P=0.002) and tumor differentiation (OR=2.21, 95% CI: 1.82–2.69, P=0.000). Subgroup analyses based on cancer type revealed that the expression of SPARCL1 had no effect on lymph node metastasis in colorectal cancer, and it did not influence tumor differentiation in gastric cancer. Egger’s test showed no evidence of publication bias (all P>0.05). Conclusion: SPARCL1 could be a novel prognostic predictive factor for GI malignancies. The expression of SPARCL1 could influence the clinicopathological features of GI malignancies. Further large-scale studies are essential to confirm SPARCL1’s prognostic predictive value, and more fundamental experimental studies are needed to illustrate the mechanisms.
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