Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy.

Glioblastoma multiforme (GBM) is the most aggressive form of glioma and the most common primary tumor of the central nervous system. Despite significant advances in clinical management strategies and diagnostic techniques for GBM in recent years, it remains a fatal disease. The current standard of care includes surgery, radiation, and chemotherapy, but the five-year survival rate for patients is less than 5%. The search for a more precise diagnosis and earlier intervention remains a critical and urgent challenge in clinical practice. The Notch signaling pathway is a critical signaling system that has been extensively studied in the malignant progression of glioblastoma. This highly conserved signaling cascade is central to a variety of biological processes, including growth, proliferation, self-renewal, migration, apoptosis, and metabolism. In GBM, accumulating data suggest that the Notch signaling pathway is hyperactive and contributes to GBM initiation, progression, and treatment resistance. This review summarizes the biological functions and molecular mechanisms of the Notch signaling pathway in GBM, as well as some clinical advances targeting the Notch signaling pathway in cancer and glioblastoma, highlighting its potential as a focus for novel therapeutic strategies.

Postoperative Bisphosphonates Use is Associated with Reduced Adverse Outcomes After Primary Total Joint Arthroplasty of Hip and Knee: A Nationwide Population-Based Cohort Study.

Bisphosphonates have been associated with a decreased risk of revision surgery after total joint arthroplasty of the hip or knee (TJA) because of their effects on decreased periprosthetic bone loss and prosthetic migration. However, the results in the early literature are inconsistent, and the influence of bisphosphonates on associated complications and subsequent TJA remains unknown. This study investigated the association between the use of bisphosphonates and the risk of adverse outcomes after primary TJA. This matched cohort study utilized the National Health Insurance Research Database in Taiwan to identify patients who underwent primary TJA over a 15-year period (January 2000-December 2015 inclusive). Study participants were further categorized into two groups, bisphosphonate users and nonusers, using propensity score matching. The Kaplan-Meier curve analysis and adjusted hazard ratios (aHRs) of revision surgery, adverse outcomes of primary surgery and subsequent TJA were calculated using Cox regression analysis. This study analyzed data from 6485 patients who underwent total hip arthroplasty (THA) and 20,920 patients who underwent total knee arthroplasty (TKA). The risk of revision hip and knee arthroplasty was significantly lower in the bisphosphonate users than in the nonusers (aHR, 0.54 and 0.53, respectively). Furthermore, the risk of a subsequent total joint arthroplasty, adverse events and all-cause mortality were also significantly reduced in the bisphosphonate users. This study, involving a large cohort of patients who underwent primary arthroplasties, revealed that bisphosphonate treatment may potentially reduce the risk of revision surgery and associated adverse outcomes. Furthermore, the use of bisphosphonates after TJA is also associated with a reduced need for subsequent arthroplasty.Research Registration Unique Identifying Number (UIN): ClinicalTrials.gov Identifier-NCT05623540 ( https://clinicaltrials.gov/show/NCT05623540 ).

The role of illness-related cognition in the relationships between resilience and depression/anxiety in nasopharyngeal cancer patients.

OBJECTIVE: Resilience has been reported as an important predictor of better mental health and prognoses in cancer patients, while its mechanisms were not clearly elucidated. In this study, we surveyed a large sample of nasopharyngeal carcinoma patients to investigate the mediating role of illness-related cognition (illness perception, stigma and meaning in life) on the associations between resilience and symptoms of anxiety and depression. METHODS: This cross-sectional study involved 773 participants diagnosed with nasopharyngeal carcinoma. Participants completed a self-reported structured questionnaire to assess their illness perception, stigma and meaning in life, resilience and symptoms of anxiety and depression. Structural equation models (SEM) were employed to explore the relationship between resilience and symptoms of anxiety and depression in the entire sample, as well as in two subgroups: Subgroup I (0-1 year since diagnosis), and Subgroup II (over 1 year since diagnosis). RESULTS: In the entire sample, after adjusting for potential confounders, illness perception, stigma and meaning in life were found to mediate the protective effect of resilience on symptoms of depression (mediating effect proportion: 65.25%) and anxiety (mediating effect proportion: 67.63%). In Subgroup I, direct effects were dominant in the associations between resilience and symptoms of anxiety (mediating effect proportion: 37.95%) and depression (mediating effect proportion: 29.13%). However, in Subgroup II, the associations between resilience and symptoms of anxiety (mediating effect proportion: 98.92%) and depression (mediating effect proportion: 81.04%) were completely mediated. CONCLUSIONS: Our study suggests that direct and indirect effects of resilience on depression and anxiety dominate in early periods (0-1 year) and long-term periods (over 1 year) following the cancer diagnosis, respectively. The findings indicate that comprehensive intervention considering both the direct effect of resilience in early stages (e.g., health education prescription and social support groups) and the indirect effects of illness cognition in long-term periods (e.g., cognitive behavioral therapies) are likely to yield the most favorable outcomes for cancer patients.

Preliminary validation of the Chinese version of the Shame and Stigma Scale among patients with facial disfigurement from nasopharyngeal carcinoma.

OBJECTIVE: This study examined the reliability and validity of a Shame and Stigma Scale (SSS) and assessed shame and stigma among patients with facial disfigurement from nasopharyngeal carcinoma (NPC). METHODS: Data were collected from 218 patients with NPC through a cross-sectional survey between January 14, 2020, and December 1, 2020. The original SSS is a 20-item scale with four dimensions (i.e., shame with appearance, sense of stigma, regret, and social/speech concern). We used Cronbach's alpha and McDonald's omega to assess reliability and exploratory factor analysis (EFA) to assess the factor structure. We also used Pearson correlation analysis to examine the relationship between each item and total score of scale items and convergent validity. RESULTS: The final 18-item SSS had a Cronbach's alpha coefficient of .89. The EFA revealed that the SSS has a four-factor structure: sense of stigma, social/speech concern, shame with appearance, and regret. These factors showed satisfactory reliability, with McDonald's omega coefficients of .87, .77, .86, and .79, respectively. The scale showed significant relationship between each item and total score of scale items with respect to item-total correlations, item-subscale correlations, and item-other-subscale correlations. Convergent validity was supported by the significant positively correlated with the total scores for depression and anxiety. CONCLUSION: The SSS is valid and reliable in assessing shame and stigma and monitoring treatment compliance among patients with NPC.

Cholesterol suppresses GOLM1-dependent selective autophagy of RTKs in hepatocellular carcinoma.

Aberrant activation of receptor tyrosine kinases (RTKs) and the subsequent metabolic reprogramming play critical roles in cancer progression. Our previous study has shown that Golgi membrane protein 1 (GOLM1) promotes hepatocellular carcinoma (HCC) metastasis by enhancing the recycling of RTKs. However, how this RTK recycling process is regulated and coupled with RTK degradation remains poorly defined. Here, we demonstrate that cholesterol suppresses the autophagic degradation of RTKs in a GOLM1-dependent manner. Further mechanistic studies reveal that GOLM1 mediates the selective autophagy of RTKs by interacting with LC3 through an LC3-interacting region (LIR), which is regulated by a cholesterol-mTORC1 axis. Lowering cholesterol by statins improves the efficacy of multiple tyrosine kinase inhibitors (TKIs) in vivo. Our findings indicate that cholesterol serves as a signal to switch GOLM1-RTK degradation to GOLM1-RTK recycling and suggest that lowering cholesterol by statin may be a promising combination strategy to improve the TKI efficiency in HCC.

Serum exosomal miR-34a as a potential biomarker for the diagnosis and prognostic of hepatocellular carcinoma.

Background: Circulating exosomal microRNAs (miRNAs) are considered as potentially non-invasive biomarkers for early detection and prognosis of cancers. Due to the lack of highly sensitive and specific molecular markers, a lot of patients with hepatocellular carcinoma are diagnosed in advanced stages. This study aims to explore the expression mode and clinical detection value of serum exosomal miR-34a in HCC, providing new potential targets and theoretical basis for the early diagnosis and prognosis monitoring of hepatocellular carcinoma. Methods: The expression of serum exosomal miR-34a in 60 HCC patients before and after operation and 60 healthy examiners was abstracted and detected by ultracentrifugation and real-time quantitative PCR. Using ROC analysis, Kaplan-Meier survival analysis and Cox regression analysis, the value of serum exosomal miR-34a on diagnosis and prognosis in HCC patients was assessed. Results: The expression level of serum exosomal miR-34a in preoperative patients was reduced significantly comparing with that in healthy examiners and postoperative patients (P<0.01; P<0.05). Moreover, the decrease of serum exosomal miR-34a was correlated significantly with differentiation degree, TNM stage, tumor infiltration depth and lymph node metastasis(P<0.05), but had no statistical differences with gender, age, ALT, AST, viral infection, cirrhosis and tumor size of HCC patients (P>0.05). At the same time, the combination of serum exosomal miR-34a and α-fetoprotein (AFP) showed high capability on diagnosis to distinguish healthy examiners and HCC patients through ROC analysis. The overall survival of patients with lower expression of serum exosomal miR-34a was worse than that of patients with high level expression by Kaplan-Meier survival analysis (P<0.05). Univariate and multivariate Cox regression analysis both showed that serum exosomal miR-34a was independently related to OS. Conclusions: Collectively, serum exosomal miR-34a is significantly down-regulated in HCC patients and might be a novel noninvasive biomarker for diagnosis and prognosis of HCC.

Chronic liver disease and cirrhosis increase morbidity in geriatric patients treated surgically for hip fractures: analysis of the US Nationwide Inpatient Sample.

BACKGROUND: This study aimed to evaluate the impact of chronic liver disease and cirrhosis on inpatient outcomes of geriatric hip fracture surgery. MATERIALS AND METHODS: Using population-based retrospective study design, this study extracted data from the US Nationwide Inpatient Sample (NIS) database 2005-2014, identifying patients aged ≥ 65 years undergoing hip fracture repair. Main outcomes were in-hospital mortality, any/specific complications, non-routine discharge, extended length of stay (LOS) and hospital costs. Associations between cirrhosis, non-cirrhotic chronic liver disease and outcomes were determined using regression analysis. RESULTS: Data of 347,363 hip fracture patients included 344,035 without liver disease, 1257 with non-cirrhotic chronic liver disease and 2,071 with cirrhosis. After adjustments, non-cirrhotic chronic liver disease was significantly associated with non-routine discharge (OR: 1.247, 95% CI: 1.038-1.498), acute kidney injury (OR: 1.266, 95% CI: 1.039-1.541), extended LOS (OR: 1.285, 95% CI: 1.122-1.473) and hospital costs (beta: 9173.42, 95% CI: 6925.9-11,420.95) compared to no liver disease; while cirrhosis was significantly associated with higher risk of in-hospital mortality (OR: 2.325, 95% CI: 1.849-2.922), any complication (OR: 1.295, 95% CI: 1.143-1.467), acute kidney injury (OR: 1.242, 95% CI: 1.177-1.433), non-routine discharge (OR: 1.650, 95% CI: 1.412-1.928), extended LOS (OR: 1.405, 95% CI: 1.263-1.562) and hospital costs (beta: 6680.24, 95% CI: 4921.53-8438.95) compared to no liver disease. CONCLUSION: In geriatric hip fracture patients undergoing surgical repair, non-cirrhotic chronic liver disease and cirrhosis independently predict non-routine discharge, acute kidney injury, prolonged LOS and greater hospital costs, and cirrhosis is also significantly associated with greater risk of any complication and in-hospital mortality.

Driver mutations of intrahepatic cholangiocarcinoma shape clinically relevant genomic clusters with distinct molecular features and therapeutic vulnerabilities.

Purpose: To establish a clinically applicable genomic clustering system, we investigated the interactive landscape of driver mutations in intrahepatic cholangiocarcinoma (ICC). Methods: The genomic data of 1481 ICCs from diverse populations was analyzed to investigate the pair-wise co-occurrences or mutual exclusivities among recurrent driver mutations. Clinicopathological features and outcomes were compared among different clusters. Gene expression and DNA methylation profiling datasets were analyzed to investigate the molecular distinctions among mutational clusters. ICC cell lines with different gene mutation backgrounds were used to evaluate the cluster specific biological behaviors and drug sensitivities. Results: Statistically significant mutation-pairs were identified across 21 combinations of genes. Seven most recurrent driver mutations (TP53, KRAS, SMAD4, IDH1/2, FGFR2-fus and BAP1) showed pair-wise co-occurrences or mutual exclusivities and could aggregate into three genetic clusters: Cluster1: represented by tripartite interaction of KRAS, TP53 and SMAD4 mutations, exhibited large bile duct histological phenotype with high CA19-9 level and dismal prognosis; Cluster2: co-association of IDH/BAP1 or FGFR2-fus/BAP1 mutation, was characterized by small bile duct phenotype, low CA19-9 level and optimal prognosis; Cluster3: mutation-free ICC cases with intermediate clinicopathological features. These clusters showed distinct molecular traits, biological behaviors and responses to therapeutic drugs. Finally, we identified S100P and KRT17 as "cluster-specific", "lineage-dictating" and "prognosis-related" biomarkers, which in combination with CA19-9 could well stratify Cluster3 ICCs into two biologically and clinically distinct subtypes. Conclusions: This clinically applicable clustering system can be instructive to ICC prognostic stratification, molecular classification, and therapeutic optimization.

Rapamycin enhances the anti-tumor activity of cabozantinib in cMet inhibitor-resistant hepatocellular carcinoma.

Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.

Evolution of congenital haemophilia care in Taiwan.

Haemophilia care in Taiwan has come a long way over the past 35 years, from the absence of specialised haemophilia treatment centres before 1984 to the establishment of treatment centers in the majority of medical centers, the listing of haemophilia as a catastrophic illness with full treatment reimbursement by the Taiwan National Health Insurance (NHI), and the implementation of full NHI coverage for prophylaxis therapy. This has led to outcome improvements such as reduced bleed-related morbidity and mortality, fewer viral infections, and enhanced overall multi-modality care. Most people with haemophilia (PWH) are now able to live normal, active lives. Early diagnosis has improved through increased awareness, physician education, and prenatal diagnosis; while comprehensive care, including state of the art rehabilitation and orthopaedic management for haemophilic arthropathy, eradication therapy for chronic hepatitis C, and better treatments for human immunodeficiency virus, allows PWH to enjoy a better quality of life and improved survival. Efforts are now being made to raise prophylaxis rates through full NHI reimbursement and the use of extended half-life recombinant factor products. Overall, Taiwan has made great strides in haemophilia care and we would like to share these experiences for the benefit of all healthcare providers involved in haemophilia care.

Directed nickel-catalyzed regio- and diastereoselective arylamination of unactivated alkenes.

Few methods have been reported for intermolecular arylamination of alkenes, which could provide direct access to important arylethylamine scaffolds. Herein, we report an intermolecular syn-1,2-arylamination of unactivated alkenes with arylboronic acids and O-benzoylhydroxylamine electrophiles with Ni(II) catalyst. The cleavable bidentate picolinamide directing group facilitates formation of stabilized 4-, 5- or 6-membered nickelacycles and enables the difunctionalization of diverse alkenyl amines with high levels of regio-, chemo- and diastereocontrol. This general and practical protocol is compatible with broad substrate scope and high functional group tolerance. The utility of this method is further demonstrated by the site-selective modification of pharmaceutical agents.

Fabrication of Iron Pyrite Thin Films and Photovoltaic Devices by Sulfurization in Electrodeposition Method.

Iron pyrite is a cheap, stable, non-toxic, and earth-abundant material that has great potential in the field of photovoltaics. Electrochemical deposition is a low-cost method, which is also suitable for large-scale preparation of iron pyrite solar cells. In this work, we prepared iron pyrite films by electrochemical deposition with thiourea and explored the effect of sulfurization on the synthesis of high-quality iron pyrite films. Upon sulfurization, the amorphous precursor film becomes crystallized iron pyrite film. Optical and electrical characterization show that its band gap is 0.89 eV, and it is an n type semiconductor with a carrier concentration of 3.01 × 1019 cm-3. The corresponding photovoltaic device shows light response. This work suggests that sulfurization is essential in the electrochemical preparation for fabricating pure iron pyrite films, and therefore for low-cost and large-scale production of iron pyrite solar cells.

Composition Profiling and Authenticity Assessment of Camellia Oil Using High Field and Low Field 1H NMR.

Camellia oil (CA), mainly produced in southern China, has always been called Oriental olive oil (OL) due to its similar physicochemical properties to OL. The high nutritional value and high selling price of CA make mixing it with other low-quality oils prevalent, in order to make huge profits. In this paper, the transverse relaxation time (T2) distribution of different brands of CA and OL, and the variation in transverse relaxation parameters when adulterated with corn oil (CO), were assessed via low field nuclear magnetic resonance (LF-NMR) imagery. The nutritional compositions of CA and OL and their quality indices were obtained via high field NMR (HF-NMR) spectroscopy. The results show that the fatty acid evaluation indices values, including for squalene, oleic acid, linolenic acid and iodine, were higher in CA than in OL, indicating the nutritional value of CA. The adulterated CA with a content of CO more than 20% can be correctly identified by principal component analysis or partial least squares discriminant analysis, and the blended oils could be successfully classified by orthogonal partial least squares discriminant analysis, with an accuracy of 100% when the adulteration ratio was above 30%. These results indicate the practicability of LF-NMR in the rapid screening of food authenticity.

Effects of Surgical Intervention for Bone Metastases on Survival in Patients with Advanced Cancer: A Nationwide Population-Based Cohort Study.

PURPOSE: With recent advances in surgical techniques and instruments, orthopedic surgeons are better equipped to treat metastatic bone disease. There has also been considerable progress in the non-surgical treatment of cancers, specifically in improving the survival rate of patients with advanced cancer. However, it remains unclear whether surgical resection of a metastatic bone lesion poses additional risk to the survival of patients with advanced cancer. PATIENTS AND METHODS: This study utilized data from the National Health Insurance Research Database (NHIRD) in Taiwan between 2000 and 2015. Patients aged ≥18 years, who had been recently diagnosed with bone metastases (BM), were enrolled and assigned to either the surgery or non-surgery groups. The demographic characteristics were analyzed, and the adjusted hazard ratios (aHR) of mortality were calculated using Cox regression analysis. RESULTS: Of the 4,549,226 individuals in the inpatient database of the NHIRD, 83,536 patients with BM were enrolled in this study. Among them, 8802 underwent surgical resection for skeletal metastatic lesion and 66,098 did not. Altogether, 28,691 patients died, including 2798 (31.8%) in the surgery group and 25,893 (39.2%) in the non-surgery group. The aHR for mortality was 0.7-fold lower in the surgery group (p < 0.001). CONCLUSION: This study demonstrates that surgical resection of metastatic bone lesions did not pose any additional risk to survival outcomes. Thus, we believe that surgery, if indicated, could have a competitive role in the management of metastatic bone disease.

Organ-specific cholesterol metabolic aberration fuels liver metastasis of colorectal cancer.

Rationale: Metastasis, the development of secondary malignant growth at a distance from a primary tumor, is the main cause of cancer-associated death. However, little is known about how metastatic cancer cells adapt to and colonize in the new organ environment. Here we sought to investigate the functional mechanism of cholesterol metabolic aberration in colorectal carcinoma (CRC) liver metastasis. Methods: The expression of cholesterol metabolism-related genes in primary colorectal tumors (PT) and paired liver metastases (LM) were examined by RT-PCR. The role of SREBP2-dependent cholesterol biosynthesis pathway in cell growth and CRC liver metastasis were determined by SREBP2 silencing in CRC cell lines and experimental metastasis models including, intra-splenic injection models and liver orthotropic injection model. Growth factors treatment and co-culture experiment were performed to reveal the mechanism underlying the up-regulation of SREBP2 in CRC liver metastases. The in vivo efficacy of inhibition of cholesterol biosynthesis pathway by betulin or simvastatin were evaluated in experimental metastasis models. Results: In the present study, we identify a colorectal cancer (CRC) liver metastasis-specific cholesterol metabolic pathway involving the activation of SREBP2-dependent cholesterol biosynthesis, which is required for the colonization and growth of metastatic CRC cells in the liver. Inhibiting this cholesterol biosynthesis pathway suppresses CRC liver metastasis. Mechanically, hepatocyte growth factor (HGF) from liver environment activates SREBP2-dependent cholesterol biosynthesis pathway by activating c-Met/PI3K/AKT/mTOR axis in CRC cells. Conclusion: Our findings support the notion that CRC liver metastases show a specific cholesterol metabolic aberration. Targeting this cholesterol biosynthesis pathway could be a promising treatment for CRC liver metastasis.

Incidence of bone metastases in patients with organ-specific cancers: A nationwide population-based cohort study.

BACKGROUND: Bones are the third most common site of metastasis, although bone metastasis (BM) incidence varies widely. This study investigated the incidence of BM in the most common cancers in Taiwan to present the recent treatment landscape in patients with organ-specific cancers. METHODS: Data from the National Health Insurance Research Database of Taiwan were used to identify adult patients diagnosed with organ-specific cancers between January 1, 2000 and December 31, 2015. Kaplan-Meier analysis was used to quantify cumulative BM incidence at follow-up. BM incidences associated with different cancers were calculated comprehensively and stratified by sex, age group and follow-up periods, and age- and sex-adjusted hazard ratios (HRs) of BM were calculated using multivariate Cox regression analysis. RESULTS: Among 938 776 participants (mean follow-up, 9.2 years), liver (19.6%), colorectal (17.1%) and lung (15.1%) cancers were most commonly associated with BM. The mean interval between a primary cancer diagnosis and BM was 2 years. BM incidence varied widely among cancers; lung cancer (3213 per 105 person-years) was associated with the highest BM risk, followed by oesophageal, prostate and breast cancer. HRs of BM were significantly higher for lung cancer (HR = 8.1) than for other cancers. CONCLUSION: The estimated BM incidence provided insight into oncological clinical practice trends in the Asia-Pacific region. BM incidence may vary among populations. Understanding the principles of clinical evaluation in patients with cancer of unknown primary origin can facilitate appropriate treatment recommendations.

S100 calcium-binding protein A9 from tumor-associated macrophage enhances cancer stem cell-like properties of hepatocellular carcinoma.

Tumor-associated macrophages (TAMs) are crucial components of the tumor microenvironment. They play vital roles in hepatocellular carcinoma (HCC) progression. However, the interactions between TAMs and HCC cells have not been fully characterized. In this study, TAMs were induced using human monocytic cell line THP-1 cells in vitro to investigate their functions in HCC progression. S100 calcium-binding protein A9 (S100A9), an inflammatory microenvironment-related secreted protein, was identified to be significantly upregulated in TAMs. S100A9 expression in tumor tissues was associated with poor survival of HCC patients. It could enhance the stem cell-like properties of HepG2 and MHCC-97H cells by activating nuclear factor-kappa B signaling pathway through advanced glycosylation end product-specific receptor in a Ca2+ -dependent manner. Furthermore, we found that, after treatment with S100A9, HepG2 and MHCC-97H cells recruited more macrophages via chemokine (CC motif) ligand 2, which suggests a positive feedback between TAMs and HCC cells. Taken together, our findings reveal that TAMs could upregulate secreted protein S100A9 and enhance the stem cell-like properties of HCC cells and provide a potential therapeutic target for combating HCC.

Value of serum tumor markers for predicting EGFR mutations in non-small cell lung cancer patients.

OBJECTIVES: We investigated whether serum tumor markers (STMs) represent a valuable noninvasive tool to predict epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. METHODS: A retrospective analysis was performed for 143 NSCLC patients at the Peking University International Hospital from December 2014 to December 2019. EGFR mutations in the tumor tissues were identified by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and next generation sequencing (NGS). The relationships between EGFR mutation and several clinicopathological features were analyzed. RESULT: EGFR mutation were found more frequently in female (56.67%, P = 0.01), never-smokers (55.26%, P = 0.004), and those with lung adenocarcinoma (ADC) (52.17%, P < 0.001). The positive mutation rate for the EGFR gene were higher in the squamous cell carcinoma antigen (SCCA)group (≤1.5 ng/ml) and in the gastrin-releasing peptide precursor (preGRP) increased group (≥69.2 pg/ml), and this difference was statistically significant (P < 0.05). Univariate logistic regression analysis demonstrated that females (Odd ratio [OR]: 2.435, 95% confidence interval [CI]: 1.232, 4.813, P = 0.01) and never-smokers (OR = 0.370; CI = 0.186, 0.734; P = 0.004), lung adenocarcinoma patients (OR = 9.091; CI = 2.599, 21.800; P = 0.001), the SCC group (≤1.5 ng/ml) (OR = 0.331, CI = 0.120, 0.914; P = 0.033), and the preGRP group (≥69.2 pg/ml) (OR = 5.478, CI = 1.462, 20.528; P = 0.012) patients were risk factors for EGFR gene mutation. Multivariate logistic regression analysis demonstrated that lung ADC and proGRP elevation were independent risk factors for predicting EGFR gene positivity (P < 0.05). CONCLUSION: STMs are associated with mutant EGFR status and could be integrated with other clinical factors to facilitate the classification of EGFR mutation status among NSCLC patients.

Analysis of Cervical Sagittal Balance in Treating Cervical Spondylotic Myelopathy: 1-Level Anterior Cervical Corpectomy and Fusion Versus 2-Level Anterior Cervical Discectomy and Fusion.

BACKGROUND Anterior cervical corpectomy and fusion (ACCF), together with anterior cervical discectomy and fusion (ACDF) are both effective clinical treatments for cervical spondylotic myelopathy (CSM). Cervical sagittal balance is critical to preserving normal alignment, and is also associated with clinical outcomes. MATERIAL AND METHODS We retrospectively reviewed patients who had suffered from CSM and had undergone 1-level ACCF or 2-level ACDF surgery between December 2016 and November 2017. Forty-eight patients were identified: 25 in the ACDF group and 23 in the ACCF group. All patients received follow-up for more than 12 months. The demographic data, radiographic parameters, and clinical efficacy were compared between and within groups, both pre- and postoperatively. RESULTS Both groups acquired good clinical efficacy; both Japanese Orthopedic Association (JOA) scores and Neck Disability Index (NDI) scores improved significantly. At the final follow-up visit, patients in the ACCF and ACDF groups did not differ significantly in C2-C7 Sagittal Vertebral Axis (cSVA), T1 Pelvic Angle (TPA), Neck Tilt (NT), Thoracic Inlet Angle (TIA), JOA, or NDI scores. However, the ACDF group had a significantly larger Cobb angle and T1 Slope (T1S) than the ACCF group. The postoperative Cobb angle increased significantly only in the ACDF group, while postoperative T1S significantly increased in both ACCF and ACDF groups. CONCLUSIONS Anterior cervical surgery may change the sagittal balance in terms of T1S or Cobb angle. No significant difference was found between ACCF and ACDF in clinical outcomes or representative global sagittal parameters. ACDF achieved more lordosis improvement than ACCF, with higher T1S. Surgeons need to pay extra attention to cervical sagittal balance, rather than focusing solely on decompression.