[Misdiagnosis of adenoid cystic carcinoma of oropharynx: a case report].

Adenoid cystic carcinoma usually occurs in the salivary glands of the head and neck. It is a malignant tumor with a high degree of malignancy, resistance to radiotherapy and chemotherapy and poor prognosis. The clinical course of adenoid cystic carcinoma is slow and easy to be misdiagnosed. The main diagnosis and treatment means are individualized and precise treatment under the multi-disciplinary consultation mode, that is, surgical treatment and radiotherapy and chemotherapy. Adenoid cystic carcinoma is prone to relapse and hematologic metastasis, and the traditional radiotherapy and chemotherapy based therapies have not achieved satisfactory efficacy in the past three decades. How to detect, diagnose and treat early is an urgent task faced by clinicians.

Surgical treatment of preauricular fistulas: a 12-year single-center clinical observation.

OBJECTIVE: This study aimed to assess the effects of surgical timing and approach on operative duration, postoperative suture removal time, and postoperative recurrence rate in the management of preauricular fistula. A 12-year single-center clinical observation was conducted to analyze the potential effects of different surgical strategies on these critical outcomes. METHODS: The clinical data from 576 (782 ears) patients who underwent surgical resection for preauricular fistulas were examined in this retrospective study. The patients were classified into various groups based on differences in operative duration, surgical techniques and the use of intraoperative magnifying equipment. Furthermore, the specific data on operative duration, postoperative suture removal time, and postoperative recurrence rate were also recorded. RESULTS: The average operative duration for 782 ears and the average time required for postoperative suture removal were determined to be (34.57 ± 4.25) min and (3.62 ± 0.76) days, respectively. Among the cases examined, recurrence occurred in 13 ears, but all of them were cured after a second surgery, resulting in a recurrence rate of 1.67% (13/782). Interestingly, the operative and postoperative suture removal time was prolonged during the infection period (P < 0.05). The postoperative recurrence rate was significantly higher in the absence of magnifying equipment, as compared to those with the use of a microscope with 2.5× magnification (P < 0.05). No statistically significant differences were noted in the recurrence rate when comparing different anesthesia methods and types of surgical incisions, as well as the intraoperative use of methylene blue, and partial removal of cartilage of the pedicle (P > 0.05). CONCLUSION: The use of methylene blue, partial removal of the cartilage of the pedicle, and surgical incision during preauricular fistula resection did not affect the operative duration, postoperative suture removal time, and postoperative recurrence rate. Therefore, surgeons can select their preferred approaches based on their individual practices and patient-specific situations. However, the use of magnifying equipment during surgery is associated with a reduced risk of recurrence.

Protection of the marginal mandibular branches of the facial nerves by different surgical procedures in comprehensive cervical lymphadenectomy for locally advanced oral and oropharyngeal cancer: a multicenter experience.

OBJECTIVE: According to the different characteristics of patients and cervical lymph node metastasis of oral and oropharyngeal cancer, the marginal mandibular branches of facial nerves were treated by different surgical procedures, and the safety and protective effects of different surgical procedures were investigated. METHODS: One hundred ninety-seven patients with oral and oropharyngeal cancer satisfying the inclusion criteria were selected. According to the different characteristics of patients and cervical metastatic lymph nodes, three different surgical procedures were used to treat the marginal mandibular branches of the facial nerve: finding and exposing the marginal mandibular branches of the facial nerves at the mandibular angles of the platysma flaps, finding and exposing the marginal mandibular branches of facial nerves at the intersections of the distal ends of facial arteries and veins with the mandible, and not exposing the marginal mandibular branches of the facial nerves. The anatomical position, injury, and complications of the marginal mandibular branches of the facial nerves were observed. RESULTS: The marginal mandibular branches of the facial nerves were found and exposed at the mandibular angles of the platysma flaps in 102 patients; the marginal mandibular branches of facial nerves were found and exposed at the intersections of the distal ends of the facial arteries and veins with the mandibles in 64 patients; the marginal mandibular branches of facial nerves were not exposed in 31 patients; among them, four patients had permanent injury of the marginal mandibular branches of the facial nerves, and temporary injury occurred in seven patients. There were statistically significant differences in the protection of the mandibular marginal branch of the facial nerve among the three different surgical methods (P = 0.0184). The best protective effect was to find and expose the mandibular marginal branch of the facial nerve at the mandibular angle of the platysma muscle flap, and the injury rate was only 2.94%. CONCLUSION: The three different surgical procedures were all safe and effective in treating the marginal mandibular branches of the facial nerves, the best protective effect was to find and expose the mandibular marginal branch of the facial nerve at the mandibular angle of the platysma muscle flap.

Optimized Detection of Unknown MET Exon 14 Skipping Mutations in Routine Testing for Patients With Non-Small-Cell Lung Cancer.

PURPOSE: MET exon 14 (METex14) skipping is an actionable biomarker in non-small-cell lung cancer. However, MET variants are highly complex and diverse, and not all variants lead to exon 14 skipping. Assessing the skipping effect of unknown variants is still a key issue in molecular diagnosis. MATERIALS AND METHODS: We retrospectively collected MET variants around exon 14 from 4,233 patients with non-small-cell lung cancer who underwent next-generation sequencing testing using DNA, as well as two published data sets. RESULTS: Among the 4,233 patients, 44 unique variants including 29 novel variants (65.9%) were discovered from 53 patients. Notably, 31 samples (58.5%) failed RNA verification. Using RNA verification, nine novel skipping variants and five nonskipping variants were confirmed. We further used SpliceAI with the delta score cutoff of 0.315 to aid the classification of novel variants (sensitivity = 98.88% and specificity = 100%). When applied to the reported variants, we also found three wrongly classified nonskipping variants. Finally, an optimized knowledge-based interpretation procedure for clinical routine was built according to the mutation type and location, and five more skipping mutations from the 13 unknown variants were determined, which improved the population determination rate to 0.92%. CONCLUSION: This study discovered more METex14 skipping variants and optimized an innovative approach that could be adapted for the interpretation of infrequent or novel METex14 variants timely without experimental validation.

EOAI, a ubiquitin-specific peptidase 5 inhibitor, prevents non-small cell lung cancer progression by inducing DNA damage.

OBJECTIVE: Targeting deubiquitinases (DUBs) has emerged as a promising avenue for anticancer drug development. However, the effect and mechanism of pan-DUB inhibitor EOAI on non-small cell lung cancer (NSCLC) remains to be studied. MATERIALS AND METHODS: The expression of ubiquitin-specific peptidase 5 (USP5) in NSCLC was evaluated by immunohistochemistry. The effect of the USP5 inhibitor, EOAI, on NSCLC cell growth and cell cycle was evaluated by CCK-8 and PI staining. Apoptosis was detected by Annexin V-FITC/PI double staining. Autophagy was examined by LC3 immunofluorescence. Comet assay and γ-H2AX immunofluorescence staining were used to detect DNA damage, and Western blotting was used to detect the expression of apoptosis, cycle, autophagy and DNA damage-related proteins. In vivo experiments demonstrated the effect of EOAI on NSCLC. RESULTS: We also found that USP5 was significantly upregulated in NSCLC tissues in this study. In addition, we show that EOAI can cause DNA damage in NSCLC cells while modulating the transcriptional activity of P53, thereby inducing cell cycle arrest in NSCLC cells, autophagy and apoptosis. In vivo experiments have shown that EOAI can inhibit tumors and synergistically enhance the anti-tumor effect of cisplatin. CONCLUSION: USP5-mediated epigenetic regulation of oncogenes promotes the occurrence of NSCLC, which provides ideas for developing potential targeted therapy.

Development and clinical applications of an enclosed automated targeted NGS library preparation system.

The rapid development of next-generation sequencing (NGS) technology has promoted its wide clinical application in precision medicine for oncology. However, laborious and time-consuming manual operations, highly skilled personnel requirements, and cross-contamination are major challenges for the clinical implementation of NGS technology-based tests. The Automated NGS Diagnostic Solutions (ANDiS) 500 system is a fully enclosed cassette-dependent automated NGS library preparation system. This platform could produce qualified targeted amplicon library in three steps with only 15 min of hands-on time. Rigorous cross-contamination test using simulated contaminant plasmids confirmed that the design of disposable cassette guarantees zero sample cross-contamination. The BRCA1 and BRCA2 mutation detection panel and gastrointestinal cancer-related gene analysis panel for the ANDiS 500 platform showed 100% accuracy and precision in detecting germ-line mutations and somatic mutations respectively. Furthermore, those panels showed 100% concordance with verified methods in a prospective cohort study enrolling 363 patients and a cohort of 45 pan-cancer samples. In conclusion, the ANDiS 500 automated platform could overcome major challenges for implementing NGS assays clinically and is eligible for routine clinical tests.

First report of furmonertinib as a first-line treatment in advanced lung adenocarcinoma patients harboring EGFR exon 20 insertion mutations after the kinase domain αC-helix: Two case reports and a literature review.

RATIONALE: Many studies have shown that first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors are less effective in patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations. The efficacy of third-generation epidermal growth factor receptor tyrosine kinase inhibitors is still under investigation. Although new targeted tyrosine kinase inhibitors and monoclonal antibody-based agents have made significant advances in the treatment of epidermal growth factor receptor exon 20 insertion (EGFR ex20ins) mutation, the efficacy of these novel agents is not quite satisfactory. Platinum- and pemetrexed-based chemotherapy remains the standard first-line treatment for patients harboring EGFR ex20ins mutation. PATIENT CONCERNS: We report for the first time 2 Chinese patients diagnosed with advanced lung adenocarcinoma with EGFR ex20ins mutations after analysis of the αC-helix sequence by next-generation sequencing. Both patients were treated with furmonertinib as the first-line therapy. INTERVENTIONS: The first case included a 38-year-old female who had an EGFR ex20ins mutation (p.S768_D770dupSVD). After 1 month of treatment with furmonertinib, her symptoms of pain and cough were significantly alleviated. She achieved a partial response according to response evaluation criteria in solid tumors.[1] The final progression-free survival was 8.13 months. The second case included a 40-year-old male who had an EGFR ex20ins mutation (p.N771_P772insVal). He had a good response to furmonertinib and exhibited stable disease according to response evaluation criteria in solid tumors with a progression-free survival of 10.90 months. OUTCOMES: Both patients experienced significant improvement in symptoms and prolonged survival after furmonertinib was used as first-line treatment. Side effects were limited but manageable. CONCLUSION: The present study indicates that furmonertinib may be a first-line treatment option for patients with non-small cell lung cancer harboring EGFR ex20ins mutation.

Repair of postoperative defects of oral cancer with submental island flaps based on vascular pedicles of different states: a multicenter retrospective study.

Submental island flap has certain advantages in repairing postoperative defects of oral cancer, and it can often achieve similar or even better effects compared with those of the free tissue flap. In this study, according to the different characteristics of patients and postoperative defects of oral cancer, submental island flaps with different states of vascular pedicle were prepared, and its repair methods, safety, and clinical effects in treating postoperative defects of oral cancer were investigated. 83 patients with oral cancer who met the inclusion criteria were selected. According to the different characteristics of the patients and postoperative defects of oral cancer, the traditional submental island flap vascular pedicle was modified into three different states: submental artery perforator flap, vascular pedicled flap with the anterior belly of digastric muscle but without the submandibular gland (SIF with anterior belly of DM), and vascular pedicled flap with the anterior belly of the digastric muscle and the submandibular gland (SIF with anterior belly of DM and SG). The types of the submental artery and the drainage vein, flap survival, and complications, were observed. The flap was successfully harvested for all patients, and the submental artery could be found or separated for all of them, with the venous drainage to the internal jugular vein in 57 (57/83, 68.67%), to the external jugular vein in 18 (18/83, 21.69%), and to the anterior jugular vein in eight (8/83, 9.64%) cases. Submental artery perforator flap was used for 11 cases, complete necrosis occurred in two cases (2/11, 18.18%), partial necrosis occurred in one case (1/11, 9.09%); SIF with anterior belly of DM was used for 49 cases, complete necrosis occurred in one case (1/49, 2.04%), partial necrosis occurred in four cases (4/49, 8.16%); SIF with anterior belly of DM and SG was used for 23 cases, including chimeric flap combining the submental island flap and the submandibular gland used for 15 cases, there were no cases of complete or partial necrosis. Submental island flap was effective in repairing postoperative defects of oral cancer. Submental island flaps with three different states of vascular pedicle could repair oral cancer-affected tissues with different defect characteristics.

Effects of p450 Polymorphisms on the Clinical Outcomes of Gefitinib Treatment in Patients with Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer.

Aims: In this study, we determined whether different genotypes of drug-metabolizing enzymes are associated with the therapeutic effects of gefitinib in non-small cell lung cancer (NSCLC). Methods: A retrospective analysis of 112 patients with stage III or IV NSCLC was performed. The clinical characteristics of these patients, including progression-free survival (PFS), outcome of gefitinib treatment, and relationship between the genotypes of rs1065852/rs2242480 and prognosis, were analyzed. Results: The rs1065852 CT/TT genotype was associated with worse prognosis than the CC type (p = 0.0306), and the median PFS was lower than that with the CC type (287 days vs. 350 days). Compared with those with CC+CC genotypes, individuals carrying T alleles (CT/TT+CT/TT) at rs1065852/rs2242480 had a poorer prognosis, and the median PFS of CT/TT+CT/TT at rs1065852/rs2242480 was significantly lower than that of the CC+CC type (188 days vs. 444.5 days). Conclusions: Genotypes of the drug-metabolizing enzymes rs1065852 and rs2242480 have an impact on the prognosis of patients with NSCLC treated with gefitinib.

Primary resistance to first- and second-generation ALK inhibitors in a non-small cell lung cancer patient with coexisting ALK rearrangement and an ALK F1174L-cis-S1189C de novo mutation: A case report.

The effectiveness of the tyrosine kinase inhibitor ALK (TKI) for non-small cell lung cancer has been confirmed. However, resistance to ALK-TKIs seems inevitable. Mutations in the ALK kinase domain have been reported as an important mechanism of acquired resistance to ALK therapy. However, patients with de novo ALK kinase domain mutations and ALK rearrangements who were not treated with ALK inhibitors have rarely been reported. Here, we report a case of primary drug resistance to first- and second-generation ALK inhibitors in a NSCLC patient with ALK-rearrangement. The next-generation sequencing test of the pathological biopsy showed that the de novo ALK kinase domain mutation F1174L-cis-S1189C may be the cause of primary drug resistance.

Predictive value of tumor-infiltrating lymphocytes detected by flow cytometry in colorectal cancer.

The high heterogeneity of tumor cells and the surrounding immune microenvironment affects the response to treatment in colorectal cancer (CRC) patients. Therefore, there is a need to identify new immune biomarkers to predict the treatment efficacy of CRC. This study aimed to explore the predictive value of tumor-infiltrating lymphocytes (TIL) for survival in CRC patients. Flow cytometry and gated analysis were performed to measure the TILs in tissue samples obtained from 536 CRC patients. The COX regression analysis showed that the CD8 + CD279+ cells had the highest impact of all evaluated TILs on postoperative disease-free survival (DFS) (P < 0.05). The optimal CD8 + CD279+ cutoff point for the prediction of survival was 12.2%. The Kaplan-Meier analysis showed significantly higher DFS in the high CD8 + CD279+ group compared with the low CD8 + CD279+ group (P < 0.05). CD8 + CD279+ cells were associated with DFS in CRC patients with the KARS mutation, MSI/MMR, perineural invasion, and those treated with neoadjuvant chemotherapy and other chemotherapeutic treatments (P < 0.05). After the multivariate adjustment, the expression of CD8 + CD279+ remained an independent risk factor for DFS. Overall, the CD8 + CD279+ cells were identified as an independent prognostic factor in CRC patients and could be used as a potential marker for postoperative DFS.

Case Report: A good response to furmonertinib second-line treatment of an advanced lung adenocarcinoma patient with a rare EGFR exon 20 N771_P772insH mutation: A case report and literature review.

Background: Lung adenocarcinoma with the classical EGFR 19 deletion and exon 21 L858R point mutations has exhibited good responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. However, the sensitivity of uncommon EGFR exon 20 insertion mutation to third-generation EGFR-TKIs has not been determined. Although emerging targeted therapies for EGFR exon 20 insertion mutation have been reported in recent years, such patients still have a poorer prognosis than those with typical or wild-type EGFR mutations. Case summary: Here, we report the case of a 57-year-old man with advanced non-small cell lung cancer (NSCLC) with a rare EGFR exon 20 N771_P772insH mutation. The patient was treated with furmonertinib as second-line therapy. Although his pleural effusion was more than before that during treatment, various examination results showed that the pleural effusion was closely related to hypoproteinemia; thus, local progression was not considered. His cough was significantly alleviated, and the dose was well tolerated. The patient was evaluated for a remarkable progression-free survival (PFS) of 10.0 months, a duration of response (DOR) of 8.0 months, and an overall survival (OS) of 22.0 months, which had not previously been achieved. Conclusion: The present study indicated that furmonertinib might be a good treatment option for first-line progressive NSCLC patients with EGFR exon 20 insertion mutation.

Case report: sequential use of almonertinib based on the EGFR exon 20 insertion mutation achieves long-term control for advanced non-small cell lung cancer patients.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) play a dominant role in the treatment of non-small cell lung cancer (NSCLC); however, to date, targeted treatment options have not been identified for patients with EGFR exon 20 insertion (ex20ins) mutations. Almonertinib, as the third generation EGFR-TKI, can irreversibly bind to EGFR ATP binding region and has a favorable therapeutic effect in EGFR + multiple targets inhibition. Almonertinib is suitable for the treatment of NSCLC patients with disease progression and T790M drug resistance mutation positive after other EGFR-TKI treatment. Case Description: We report the case of a female patient with NSCLC with an EGFR ex20ins mutation (p.Ala767_Val769dup) identified by next-generation sequencing (NGS). The patient received systemic chemotherapy after surgical resection of the lesion. After the progression of first-line chemotherapy, the patient received sequential targeted therapy with afatinib and poziotinib, achieving progression-free survival (PFS) of 3.2 and 10.4 months, respectively. After the progression, we chose almonertinib when the patient refused to re-chemotherapy. Under the treatment of almonertinib, the PFS time of the patient reached 14 months. Conclusions: Almonertinib had the most substantial effect, and its use has not been previously reported for NSCLC patients with EGFR ex20ins mutations. The successful application of almonertinib reported here indicates that is a potential new treatment regimen for patients with EGFR ex20ins mutations.

Reactive Oxygen Species Bridge the Gap between Chronic Inflammation and Tumor Development.

According to numerous animal studies, adverse environmental stimuli, including physical, chemical, and biological factors, can cause low-grade chronic inflammation and subsequent tumor development. Human epidemiological evidence has confirmed the close relationship between chronic inflammation and tumorigenesis. However, the mechanisms driving the development of persistent inflammation toward tumorigenesis remain unclear. In this study, we assess the potential role of reactive oxygen species (ROS) and associated mechanisms in modulating inflammation-induced tumorigenesis. Recent reports have emphasized the cross-talk between oxidative stress and inflammation in many pathological processes. Exposure to carcinogenic environmental hazards may lead to oxidative damage, which further stimulates the infiltration of various types of inflammatory cells. In turn, increased cytokine and chemokine release from inflammatory cells promotes ROS production in chronic lesions, even in the absence of hazardous stimuli. Moreover, ROS not only cause DNA damage but also participate in cell proliferation, differentiation, and apoptosis by modulating several transcription factors and signaling pathways. We summarize how changes in the redox state can trigger the development of chronic inflammatory lesions into tumors. Generally, cancer cells require an appropriate inflammatory microenvironment to support their growth, spread, and metastasis, and ROS may provide the necessary catalyst for inflammation-driven cancer. In conclusion, ROS bridge the gap between chronic inflammation and tumor development; therefore, targeting ROS and inflammation represents a new avenue for the prevention and treatment of cancer.

Study on reducing carbon dioxide and harmful emissions of diesel-ignited natural gas engine.

Natural gas (NG) is a clean and low-carbon fuel and the NG engine is one of the main measures used by the public transportation industry to achieve carbon peak targets. However, NG engines have problems, such as ignition difficulty and low thermal efficiency. The use of diesel to ignite NG is an effective solution to these problems; however, this solution will increase CO2 emissions compared with NG engines. In this study, the potential of reducing CO2 emissions from a diesel-pilot-ignited (DPI) NG engine by optimizing the injection parameters (injection pressure and injection timing) under different loads is studied through experiments. Furthermore, the formation mechanism of CO2 in combination with chemical kinetics is analyzed. The results show that combustion in the DPI mode presents an obvious two-stage heat release and its CO2 emission is 17.15% lower than that of pure diesel combustion (PDC). Under high-load conditions, as the diesel injection pressure increase, the THC and NOX emissions emissions decrease by 67.53% and 84.32%. As the diesel injection timing (DIT) advances, the NOX emissions increase from 1.84 to 22.96 g/kW·h respectively. According to the analysis of the chemical kinetic mechanism, the formation of CO2 in DPI mode is primarily through the reaction of CO + O2 = CO2 + O, whereas in conventional diesel combustion (CDC) mode, CO2 is formed through the reaction of CO + OH = CO2 + H. Within the range of -18 to -5°CA ATDC DIT, increasing the diesel injection pressure (DIP) or advancing the DIT can improve the thermal efficiency of DPI NG engines and reduce CO2 emissions.

Clinicopathologic characteristics and diagnostic methods of RET rearrangement in Chinese non-small cell lung cancer patients.

Background: Rearranged during transfection (RET) rearrangement has been identified as one of the crucial oncogenic drivers in non-small cell lung cancer (NSCLC). Recently, two highly selective RET inhibitors have been approved by the US Food and Drug Administration and demonstrated remarkable responses. However, the clinical characteristics, outcomes and optimal diagnostic method of RET-rearrangements are not well understood. This study sought to evaluate the prevalence and characteristics of RET rearrangement, identify an effective diagnostic method for it, and correlate its presence with outcomes. Methods: A total of 9,431 Chinese NSCLCs from two cancer centers who have undertaken targeted DNA-NGS were enrolled and 167 RET-positive cases were screened. Non-canonical RET rearrangements were confirmed by targeted RNA-NGS. If material was sufficient, positive cases were analyzed by fluorescence in situ hybridization (FISH) (n=30) and immunohistochemistry (IHC) (n=57). Clinicopathologic characteristics, molecular profiling and treatment outcomes of RET rearrangement were evaluated. Results: The prevalence of RET rearrangement was 1.52% (138/9,101) in unfiltered cases and 8.79% (29/330) in EGFR/KRAS/BRAF/ALK-negative cases. RET rearrangement was common in females, never smokers, and lung adenocarcinoma patients. Additionally, 40.3% of stage IV RET-rearranged NSCLC patients developed brain metastases. TP53 was the most common concurrent mutation, and 8 patients harbored concurrent driver oncogenic alterations, including EGFR (N=5), KRAS (N=2), and ALK (N=1). Non-canonical fusion partners were identified in 13.8% (23/167) of cases by DNA-based NGS, and RNA-based NGS identified 3 new partners (EPS8, GOLGA5, and TNIP1). The concordance of FISH and NGS was 83.3% (25/30), while the concordance of IHC and NGS was only 28.1% (16/57). Both IHC and FISH demonstrated lower sensitivity for NCOA4-/other-RET fusions. The CCDC6-RET subgroup had significantly longer progression-free survival than the KIF5B-RET subgroup, both after chemotherapy (23 vs. 9.7 months; P=0.014). Conclusions: RET rearrangement occurs in 1.52% of Chinese NSCLCs and has identifiable clinicopathologic characteristics. RET IHC has a low sensitivity, disavowing its use in routine practice. While NGS and FISH has good performance in identifying RET rearrangement. Both IHC and FISH demonstrated lower sensitivity for NCOA4-/others-RET fusions. Clinical benefit with chemotherapy is different between CCDC6-RET and KIF5B-RET fusion patients, optimal treatment should be considered when selecting therapies for patients with RET-rearranged lung cancers.

Autoantibody Against Ferritin Light Chain is a Serum Biomarker for the Detection of Liver Cirrhosis but Not Liver Cancer.

Purpose: Ferritin is a protein that plays an important role in iron metabolism, it consists of two subunits: heavy chain (FTH) and light chain (FTL). Elevated expression of FTL is observed in multiple malignancies. Recent studies have found that the frequency of circulating autoantibody against FTL (anti-FTL) increased significantly in hepatocellular carcinoma (HCC). The aim of this study is to verify circulating anti-FTL as a biomarker for the early detection of HCC. Patients and Methods: A total of 1565 participants were enrolled and assigned to two independent validation cohorts, including 393 HCC patients, 379 liver cirrhosis (LC) patients, 400 chronic hepatitis (CH) patients, and 393 healthy subjects. The concentration of serum anti-FTL was measured by indirect Enzyme-Linked Immunosorbent Assay (ELISA). Kruskal-Wallis test was used to compare anti-FTL concentrations between HCC group and three control groups. Percentile 95 of anti-FTL absorbance value of healthy group was selected as the cut-off value to calculate the positive rate in each group. The area under receiver operating characteristic curve (AUC) was used to quantitatively describe its diagnostic value. Results: The median concentration of anti-FTL in HCC patients was higher than that in CH patients and healthy subjects, but there was no difference between HCC patients and LC patients. Further analysis showed that there was no difference between early stage LC, advanced stage LC, Child-Pugh A HCC, Child-Pugh B HCC and Child-Pugh C HCC. The positive rate of anti-FTL was 12.2% (48/393) in HCC, 13.5% (51/379) in LC, 6.3% (25/400) in CH and 5.1% (20/393) in healthy subjects, respectively. The AUC of anti-FTL to distinguish LC from CH or healthy subjects were 0.654 (95% CI: 0.615-0.692) and 0.642 (95% CI: 0.602-0.681), respectively. Conclusion: Anti-FTL is not a biomarker for the early diagnosis of HCC due to specificity deficiency, but may be helpful for the early detection of LC.

Synergistic Effect of La and TiB2 Particles on Grain Refinement in Aluminum Alloy.

Synergistic effect of TiB2 (in form of Al-5Ti-1B) and La on grain refining results in Al-2Cu alloy was investigated. α-Al grains are significantly refined by Al-5Ti-1B. When trace La is added to the melt, further refinement is exhibited. Average grain size and nucleation undercooling of α-Al reduce first and then almost remain unchanged with La addition. Satisfactory grain refining result achieves when La addition level reaches 600 ppm. When more than 600 ppm La is added to the melt, La-rich particles form and the effect of solute La left in matrix on the microstructure almost no longer changes. Theoretical calculation results demonstrate that solute La segregates to Al melt/TiB2 particles interface along with Ti and Cu prior to α-Al nucleation and the synergistic effect of La and TiB2 particles on grain refinement mainly attributes to the enhancement in the potency of TiB2 particles to heterogeneously nucleate α-Al by trace La addition.

Periplogenin suppresses the growth of esophageal squamous cell carcinoma in vitro and in vivo by targeting STAT3.

The mortality rate of esophageal squamous cell carcinoma (ESCC) is higher than that of other cancers worldwide owing to a lack of therapeutic targets and related drugs. This study aimed to find new drugs by targeting an efficacious therapeutic target in ESCC patients. Signal transducer and activator of transcription 3 (STAT3) is hyperactive in ESCC. Herein, we identified a novel STAT3 inhibitor, periplogenin, which strongly inhibited phosphorylation of STAT3 at Tyr705. Docking models and pull-down assays revealed that periplogenin bound directly and specifically to STAT3, leading to significant suppression of subsequent dimerization, nuclear import, and transcription activities. In addition, STAT3 knockdown cell lines were insensitive to periplogenin, whereas in contrast, STAT3-overexpressing cells were more sensitive to periplogenin, indicating that STAT3 was a target of periplogenin. Intraperitoneally administered periplogenin exhibited efficacious therapeutic effects in ESCC patient-derived xenograft models and dramatically impaired the phosphorylation of STAT3 and expression levels of STAT3-mediated downstream genes. Thus, our study demonstrated that periplogenin acted as a new STAT3 inhibitor, suppressing the growth of ESCC in vitro and in vivo, providing a basis for its potential application in ESCC treatment and prevention.

Cell-free DNA from cerebrospinal fluid can be used to detect the EGFR mutation status of lung adenocarcinoma patients with central nervous system metastasis.

BACKGROUND: EGFR tyrosine kinase inhibitors (TKIs) have revolutionized the therapeutic approach for EGFR mutated patients. However, acquired resistance to EGFR-TKI therapy is unavoidable. Repeat biopsy cannot be used, and peripheral blood detection shows a low positive rate in cases of brain-only disease progression. METHODS: Droplet digital polymerase chain reaction (PCR) (ddPCR) was performed on the plasma and cerebrospinal fluid (CSF) samples of 79 lung adenocarcinoma (LUAD) patients with EGFR mutations and central nervous system (CNS) metastasis. The differences in the EGFR mutation status between the paired plasma and CSF samples were assessed, and the role of CSF testing as a predictor of overall survival was evaluated. RESULTS: The CSF of patients with neurological symptoms, EGFR-TKI treatment, or leptomeningeal metastasis (LM) had a significantly higher positive rate of EGFR mutation compared to the plasma samples (P=0.001, P=0.035, P=0.019, respectively). Moreover, EGFR mutation status in CSF was consistent with neurological symptoms and LM (kappa =0.455, P<0.001; kappa =0.508, P<0.001; respectively). For the patients with brain metastasis, EGFR mutation-positive rate in CSF samples was lower than that in plasma samples (28.3% vs. 64.2%, P<0.001), while the patients with LM had the opposite result (84.6% vs. 38.5%, P=0.004). Moreover, patients with EGFR mutation in their CSF experienced worse survival [hazard ratio (HR) =2.93, 95% confidence interval (CI): 1.45-5.92; P=0.003, P adjust <0.0001]. CONCLUSIONS: The EGFR mutation status of CSF was different from that of plasma and is correlated with patient prognosis. CSF could be helpful in detecting the EGFR mutation status of patients, particularly in cases of LM.