The Value of Ki-67 Labeling Index in Central Lymph Node Metastasis and Survival of Papillary Thyroid Carcinoma: Evidence From the Clinical and Molecular Analyses.

BACKGROUND: Recent evidence suggests that the Ki-67 labeling index is associated with lymph node metastasis and the prognosis of papillary thyroid carcinoma (PTC). METHODS: We retrospectively evaluated the clinicopathological features of consecutive PTC patients between Jan 2019 and Oct 2020 in our medical center. The molecular analysis was also conducted by using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) program. The Chi-square test was performed for the comparison of variables between patients with central lymph node metastasis (CLNM) and not. Besides, univariate and stepwise multivariate logistic regression analyses were further used to determine the risk factors for CLNM in PTC. RESULTS: Our results showed that male gender (odd ratio (OR) = 3.02; 95% CI: 1.81-5.04), tumor size >1 cm (OR = 2.81; 95% CI: 1.84-4.29), multifocality (OR = 2.08; 95% CI: 1.31-3.30, and Ki-67 labeling index (>3% and ≤5%: OR = 1.20; 95% CI: .73-1.97; >5%: OR = 3.85; 95% CI: 1.62-9.14) were independent risk factors for CLNM. After excluding the patients with harvested central lymph nodes <3, increased Ki-67 labeling index was still associated with the number of CLNM and the lymph node ratio. Additionally, the expression level of Ki-67 was significantly correlated with a higher N stage and worse disease-free survival in TCGA and validated GSE60542 datasets. CONCLUSIONS: Higher Ki-67 labeling index (>5%) is significantly associated with the CLNM in PTC patients, like other indicators of the male gender, larger tumor size, and multifocality. Besides, the Ki-67 was also determined to be associated with CLNM and DFS in PTC patients, which may act as an important molecular marker in PTC.

Is Age ≥ 55 years an optimal cutoff point among patients with differentiated thyroid Microcarcinoma? a preliminary study.

PURPOSE: Age ≥ 55 years is regarded as a pivotal component of TNM stage classification in differentiated thyroid carcinoma (DTC). However, whether this cutoff point is still adaptable for differentiated thyroid microcarcinoma (DTMC) is rarely investigated. METHODS: We reviewed and analyzed the data of DTC patients aged ≥ 55 years from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analyses were used to determine the potential risk factors of cancer-specific survival (CSS) in DTMC patients aged ≥ 55 years. The Kaplan-Meier survival curves were used to estimate CSS probability. Receiver operating characteristic (ROC) curves were used to analyze the best age cutoff point for DTMC. RESULTS: Among the DTMC patients, there was no significant difference in the 1-, 3-, 5-, and 7-year CSS probability between the 55-59 years and 60-64-years subgroup (p = 0.72). The ROC curves indicated that 65 years, 65 years, and 64 years were the cutoff age point of 3-, 5-, and 7-year CSS probability in DTMC patients, respectively. Besides, N1b (Hazard ratio (HR) = 3.90, 95% Confidence interval (CI): 2.01-7.57; p < 0.001), extrathyroidal extension (HR = 2.53, 95 %CI: 1.39-4.62; p = 0.002), and M1 (HR = 11.42, 95 %CI: 5.04-25.90; p < 0.001) were the independent risk factors in CSS of DTMC patients. CONCLUSIONS: Our results suggested age at diagnosis ≥ 55 years is not the best cutoff point in stratifying the stage of the DTMC patients. On the contrary, those patients aged above 65 years have a significantly lower probability of CSS, which perhaps should be taken into consideration for treatment decision-making.

Safety and Immunogenicity of Inactivated and Recombinant Protein SARS-CoV-2 Vaccines in Patients With Thyroid Cancer.

Background: This study aimed at assessing the safety and immunogenicity of SARS-CoV-2 vaccines in patients with thyroid cancer. Methods: This observational study included thyroid cancer patients between April 1, 2021, and November 31, 2021, in the Second Affiliated Hospital of Chongqing Medical University. All participants received at least one dose of the SARS-CoV-2 vaccine. SARS-CoV-2 IgG was tested, and the interval time between the last dose and humoral response test ranged from <1 to 8 months. The complications after SARS-CoV-2 vaccines were recorded. Results: A total of 115 participants at least received one dose of SARS-CoV-2 vaccines with a 67.0% IgG-positive rate. Among them, 98 cases had completed vaccination, and the positivity of SARS-CoV-2 IgG antibodies was 96% (24/25) with three doses of ZF2001. SARS-CoV-2 IgG antibodies' positivity was 63.0% (46/73) of two doses of CoronaVac or BBIBP-CorV vaccine. Additionally, after 4 months of the last-dose vaccination, the IgG-positive rate (31.6%, 6/19) significantly decreased in thyroid cancer patients. The IgG-positive rate (81.0%, 64/79) was satisfactory within 3 months of the last-dose vaccination. Ten (10.2%) patients had side effects after SARS-CoV-2 vaccination. Among them, two (2.0%) patients had a fever, five (5.1%) patients had injection site pain, one (1.0%) patient felt dizzy, and one patient felt dizzy and had injection site pain at the same time. Conclusion: SARS-CoV-2 vaccines (CoronaVac, BBIBP-CorV, and ZF2001) are safe in thyroid cancer patients. The regression time of SARS-CoV-2 IgG is significantly shorter in thyroid cancer patients than in healthy adults. Therefore, a booster vaccination dose may be earlier than the systematic strategy for thyroid cancer patients.

Identifying and Validating of an Autophagy-Related Gene Signature for the Prediction of Early Relapse in Breast Cancer.

BACKGROUND: Compelling evidence has demonstrated the pivotal role of autophagy in the prognosis of breast cancer. Breast cancer (BC) patients with early relapse consistently exhibited worse survival. METHODS: The autophagy-related genes were derived from the Human Autophagy Database (HADb) and high-sequencing data were obtained from The Cancer Genome Atlas (TCGA). Discrepantly expressed autophagy genes (DEAGs) between early relapse and long-term survival groups were performed using the Linear Models for Microarray data (LIMMA) method. Lasso Cox regression analysis was conducted for the selection of the 4-gene autophagy-related gene signature. GSE42568 and GSE21653 databases were enrolled in this study for the external validation of the signature. Then patients were divided into high and low-risk groups based on the specific score formula. GSEA was used to discover the related signaling pathway. The Kaplan-Meier curves and the receiver operating characteristic (ROC) curves were used to evaluate the discrimination and accuracy of the 4-gene signature. RESULTS: A signature composed of four autophagy-related mRNA including APOL1, HSPA8, SIRT1, and TP73, was identified as significantly associated with the early relapse in BC patients. Time-dependent receiver-operating characteristic at 1 year suggested remarkable accuracy of the signature [area under the curve (AUC = 0.748)]. The risk score model based on the autophagy-related signature showed favorable predicting value in 1-, 2-, and 3-year relapse-free survival (RFS) in training and two validating cohorts. The GSEA displayed gene sets were remarkably enriched in carcinogenic activation pathways and autophagy-related pathways. The nomogram involving three variables (progesterone receptor status, T stage, and 4-gene signature) exhibited relatively good discrimination with a C-index of 0.766. CONCLUSIONS: Our study establishes an autophagy-related 4-gene signature that can effectively stratify the high-risk and low-risk BC patients for early relapse. Combined with the clinicopathological variables, the signature could significantly help oncologists tailor more efficient treatment strategies for BC patients.

Protective effects of autophagy and NFE2L2 on reactive oxygen species-induced pyroptosis of human nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is characterized by the decrease of nucleus pulposus cells (NPCs). With the increase of the degree of degeneration, the reactive oxygen species (ROS) in nucleus pulposus tissue increases. Pyroptosis is a newly discovered form of cell death and its relationship with oxidative stress in NPCs remains unclear. This study was performed to investigate the mechanisms of pyroptosis of NPCs under oxidative stress. NPCs were isolated from IDD patients by surgical treatment. Pyroptosis related proteins like NLR family pyrin domain containing 3(NLRP3) and PYD and CARD domain containing (PYCARD) were detected by western blot, and membrane pore formation was observed by hochest33342/PI double staining or scanning electron microscope. The results showed that ROS induced the pyroptosis of NPCs and it depended on the expression of NLRP3 and PYCARD. The increased ROS level also increased transcription factor nuclear factor, erythroid 2 like 2 (NFE2L2, Nrf2) and the autophagy of NPCs, both of which attenuated the pyroptosis. In summary, ROS induces the pyroptosis of NPCs through the NLRP3/ PYCARD pathway, and establishes negative regulation by increasing autophagy and NFE2L2. These findings may provide a better understanding of the mechanism of IDD and potential therapeutic approaches for IDD treatment.

Propionibacterium acnes induces intervertebral disc degeneration by promoting nucleus pulposus cell pyroptosis via NLRP3-dependent pathway.

Recent evidence suggests that Propionibacterium acnes (P. acnes) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD), however, whose mechanism remains unclear. A key component of inflammatory responses to P. acnes appears to be interleukin (IL)-1ß, which has been proved to be high expression in degenerative nucleus pulposus cells (NPCs). This study aimed to explore the inflammatory mechanism driving the host response to P. acnes infection in IVDD. Our data demonstrated that the number of nod-like receptor protein 3 (NLRP3)-positive cells was significantly increased in the P. acnes-infected nucleus pulposus (NP) tissue. Meanwhile, the up-regulated expressions of NLRP3, caspase-1, caspase-5, IL-1ß, IL-18, Gasdermin D (GSDMD) were observed in NPCs after co-culturing with P. acnes, which suggested NPCs pyroptosis activation induced by P. acnes. To further investigate the underlying mechanisms, NLRP3 inflammasome inhibitor MCC950 and thioredoxin binding protein (TXNIP)-siRNA were used. With the addition of MCC950 to NPCs co-cultured with P. acnes in vitro, the secretions of mature IL-1ß and IL-18 were reduced. Moreover, these MCC950-mediated effects were repeated by siRNA-transfected TXNIP knockdown. These results implied P. acnes activated inflammatory response by the TXNIP-NLRP3 pathway. To further reveal the anti-degeneration role of MCC950 in vivo, MCC950 was injected into the rabbit IVDD models infected by P. acnes. The MRI and histological detection provided more solid evidence that MCC950 treatment effectively retarded the degenerative process of the intervertebral discs in vivo. In summary, these results suggest that P. acnes-induced NPCs pyroptosis activation via the NLRP3-dependent pathway is likely responsible for the inflammatory pathology of IVDD. MCC950 can alleviate inflammatory injury and NPCs pyroptosis under P. acnes infection and may delay the progression of disc degeneration, which provides a new direction for the treatment of IVDD.

HO-1 overexpression alleviates senescence by inducing autophagy via the mitochondrial route in human nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is closely associated with aging. Our previous studies have confirmed that heme oxygenase-1 (HO-1) can inhibit nucleus pulposus (NP) cell apoptosis. However, whether or not HO-1 is involved in NP cell senescence and autophagy is unclear. Our results indicated that HO-1 expression was reduced in IDD tissues and replicative senescent NP cells. HO-1 overexpression using a lentiviral vector reduced the NP cell senescence level, protected mitochondrial function, and promoted NP cell autophagy through the mitochondrial pathway. Autophagy inhibitor 3-MA pretreatment reversed the anti-senescent and protective effects on the mitochondrial function of HO-1, which promoted the degradation of the extracellular matrix (ECM) in the intervertebral disc. In vivo, HO-1 overexpression inhibited IDD and enhanced autophagy. In summary, these results suggested that HO-1 overexpression alleviates NP cell senescence by inducing autophagy via the mitochondrial route.

[Therapeutic evaluation of intertransverse bone graft for single segmental thoracic spinal tuberculosis].

OBJECTIVE: ?To explore the effectiveness of intertransverse bone graft after debridement and fusion combined with posterior instrumentation in patients with single segmental thoracic tuberculosis. METHODS: ?Between March 2014 and May 2015, 17 cases of thoracic tuberculosis were treated by the surgery of intertransverse bone graft after debridement and fusion combined with posterior instrumentation. There were 10 males and 7 females with an average age of 48.5 years (range, 18-70 years), and with a mean disease duration of 4 months (range, 1-9 months). The affected segments included T4, 5 in 2 cases, T6, 7 in 5 cases, T7, 8 in 3 cases, T9, 10 in 2 cases, T10, 11 in 4 cases, and T11, 12 in 1 case. The operation time, intraoperative blood loss, and hospitalization time were recorded. Postoperative plain radiography was taken to assess the decompression and internal fixation, and the fusion effect was evaluated by X-ray or CT examination. The erythrocyte sedimentation rate (ESR), C reactive protein (CRP), visual analogue scale (VAS), Oswestry disability index (ODI), and Kyphosis angle were recorded and compared; the nerve function was evaluated by American Spinal Injury Association (ASIA). RESULTS: ?The mean operation time, intraoperative blood loss, and hospitalization time were 184 minutes (range, 165-220 minutes), 231 mL (range, 150-800 mL), and 18 days (range, 12-26 days) respectively. No complication of hematoma or wound dehiscence was found. All patients were followed up 17.9 months on average (range, 9-22 months). No bone graft failure, internal fixation broken, pleural effusion, cerebrospinal fluid leakage, wound infection, fistula formation, and other complications occurred. Satisfactory intervertebral fusion was obtained in all patients at 3-8 months (mean, 5.3 months) after surgery. The ESR, CRP, VAS score, ODI score, and Kyphosis angle were significantly improved at immediate after operation and last follow-up when compared with preoperative ones (P<0.05), and the ESR, CRP, VAS score and ODI score at last follow-up were significantly better than those at immediate after operation (P<0.05). At last follow-up, the nerve function was recovered to ASIA grade E from grade C (1 case) and grade D (6 cases). CONCLUSIONS: ?Intertransverse bone graft is a reliable, safe, and effective way of bone graft applied to the single segmental thoracic spinal tuberculosis.