Krüppel-like Factor 10 as a Prognostic and Predictive Biomarker of Radiotherapy in Pancreatic Adenocarcinoma.

The prognosis of pancreatic adenocarcinoma (PDAC) remains poor, with a 5-year survival rate of 12%. Although radiotherapy is effective for the locoregional control of PDAC, it does not have survival benefits compared with systemic chemotherapy. Most patients with localized PDAC develop distant metastasis shortly after diagnosis. Upfront chemotherapy has been suggested so that patients with localized PDAC with early distant metastasis do not have to undergo radical local therapy. Several potential tissue markers have been identified for selecting patients who may benefit from local radiotherapy, thereby prolonging their survival. This review summarizes these biomarkers including SMAD4, which is significantly associated with PDAC failure patterns and survival. In particular, Krüppel-like factor 10 (KLF10) is an early response transcription factor of transforming growth factor (TGF)-ß. Unlike TGF-ß in advanced cancers, KLF10 loss in two-thirds of patients with PDAC was associated with rapid distant metastasis and radioresistance; thus, KLF10 can serve as a predictive and therapeutic marker for PDAC. For patients with resectable PDAC, a combination of KLF10 and SMAD4 expression in tumor tissues may help select those who may benefit the most from additional radiotherapy. Future trials should consider upfront systemic therapy or include molecular biomarker-enriched patients without early distant metastasis.

Effective Surface Modification of 2D MXene toward Thermal Energy Conversion and Management.

Thermal energy management is a crucial aspect of many research developments, such as hybrid and soft electronics, aerospace, and electric vehicles. The selection of materials is of critical importance in these applications to manage thermal energy effectively. From this perspective, MXene, a new type of 2D material, has attracted considerable attention in thermal energy management, including thermal conduction and conversion, owing to its unique electrical and thermal properties. However, tailored surface modification of 2D MXenes is required to meet the application requirements or overcome specific limitations. Herein, a comprehensive review of surface modification of 2D MXenes for thermal energy management is discussed. First, this work discusses the current progress in the surface modification of 2D MXenes, including termination with functional groups, small-molecule organic compound functionalization, and polymer modification and composites. Subsequently, an in situ analysis of surface-modified 2D MXenes is presented. This is followed by an overview of the recent progress in the thermal energy management of 2D MXenes and their composites, such as Joule heating, heat dissipation, thermoelectric energy conversion, and photothermal conversion. Finally, some challenges facing the application of 2D MXenes are discussed, and an outlook on surface-modified 2D MXenes is provided.

The significance of systematic lymph node dissection in surgery for early-stage non-small cell lung cancer patients aged ≤40 years.

BACKGROUND: Surgery remains the best option for treating early-stage non-small cell lung cancer (NSCLC), and lymph node dissection (LND) is an important step in this approach. However, the extent of LND in the general age population, especially in young patients, is controversial. This retrospective study aimed to investigate the correlation between systematic lymph node dissection (SLND) and prognosis in young (≤40 years) patients with stage IA NSCLC. METHODS: Clinicopathological data of 191 patients aged ≤40 years who underwent surgical pulmonary resection for stage IA NSCLC between January 2010 and December 2016 were retrospectively collected. Of the patients, 104 received SLND (SLND group), while the other 87 patients underwent sampling or no LND (non-SLND group). The disease-free survival (DFS) and overall survival (OS) curves of the patients from each group were plotted using the Kaplan-Meier method, and the correlations of the patients' clinical factors with prognosis were also analyzed. RESULTS: The median follow-up period was 55 months. During follow-up, 7 patients died, and recurrence or metastasis was detected in 16 patients. Kaplan-Meier analysis revealed no difference in DFS (P=0.132) between the SLND and non-SLND group, but a significant difference was found between the groups in OS (P=0.022). Additionally, there was no statistically pronounced difference in OS or DFS between male and female patients. Multivariate survival analysis showed that the type of SLND, as well as tumor size, is an independent prognostic factor for DFS (HR, 3.530; 95% CI, 1.120-11.119; P=0.031) and OS (HR, 13.076; 95% CI, 1.209-141.443; P=0.034). CONCLUSIONS: For young (age ≤40) stage IA NSCLC patients with pathological invasive adenocarcinoma, intraoperative SLND can improve the DFS and OS. Further studies are needed to verify the most optimal degree of LND in young patients.

Relationship between Methylation of FHIT and CDH13 Gene Promoter Region and Liver Cancer.

In order to demonstrate the relationship between methylation of fragile histidine triad (FHIT) and T-cadherin/H-cadherin (CDH13) genes and liver cancer, the methylation status of FHIT and CDH13 was detected in healthy individuals and in Mongolian and Han patients with liver cancer. The phenol-chloroform method was used to extract genomic DNA. The methylation specific polymerase chain reaction method was applied to detect the methylation status of FHIT and CDH13. The relationship between smoking and alcohol consumption and gene (FHIT and CDH13) methylation was analyzed. There was significant difference in methylation rate of FHIT (72.67%, 34.67%) and CDH13 (72.0%, 28.0%) between liver cancer patients and healthy individuals of Mongolian descent (P<0.05), as well as that of FHIT (68%, 30.67%) and CDH13 (64%, 26%) between liver cancer patients and healthy individuals of Han individuals (P<0.05). There was also a relationship between smoking and drinking and the methylation of FHIT and CDH13 (P<0.05). Thus, the methylation of FHIT and CDH13 had a relationship with liver cancer incidence. Smoking and alcohol ingestion may promote the methylation of FHIT and CDH13.

[Study of genetic susceptibility in 198 children with asthma].

OBJECTIVE: To analyze the frequency distribution of single nucleotide polymorphisms (SNPs) of four asthma-related gene loci (ACE I/D; ADRB2 Arg16Gly; TNF-α G-308A; MS4A2 Glu237Gly) in 198 asthmatic children, and to investigate its association with genetic susceptibility to childhood asthma and some clinical phenotypes of asthma. METHODS: Polymerase chain reaction product electrophoresis identification and real-time quantitative PCR detecting system were used to determine the frequency distributions of the SNPs of the four asthma-related gene loci in 198 asthmatic children and 110 healthy controls. The serum total IgE (TIgE) levels and blood eosinophil proportion (%EOS) of the asthmatic children were measured. Different genotypes at the four asthma-related gene loci were compared in terms of TIgE and %EOS. RESULTS: The genotype DD of angiotensin-converting enzyme (ACE) had a significantly higher frequency in the asthmatic children than in the healthy controls (χ2= 30.667, P<0.01), and the frequency of D allele was also significantly higher in the asthmatic children than in the healthy controls (χ2=7.151, P<0.01). No correlation was found between the polymorphism of each gene locus and serum TIgE level and %EOS (P>0.05). CONCLUSIONS: Genotype DD of ACE is related to genetic susceptibility to childhood asthma and may be the risk factor for childhood asthma.

Gastrin inhibits a novel, pathological colon cancer signaling pathway involving EGR1, AE2, and P-ERK.

Human anion exchanger 2 (AE2) is a plasma membrane protein that regulates intracellular pH and cell volume. AE2 contributes to transepithelial transport of chloride and bicarbonate in normal colon and other epithelial tissues. We now report that AE2 overexpression in colon cancer cells is correlated with expression of the nuclear proliferation marker, Ki67. Survival analysis of 24 patients with colon cancer in early stage or 33 patients with tubular adenocarcinoma demonstrated that expression of AE2 is correlated with poor prognosis. Cellular and molecular experiments indicated that AE2 expression promoted proliferation of colon cancer cells. In addition, we found that transcription factor EGR1 underlies AE2 upregulation and the AE2 sequester p16INK4a (P16) in the cytoplasm of colon cancer cells. Cytoplasmic P16 enhanced ERK phosphorylation and promoted proliferation of colon cancer cells. Gastrin inhibited proliferation of colon cancer cells by suppressing expression of EGR1 and AE2 and by blocking ERK phosphorylation. Taken together, our data describe a novel EGR1/AE2/P16/P-ERK signaling pathway in colon carcinogenesis, with implications for pathologic prognosis and for novel therapeutic approaches.

[Establishment of in vitro microtest for determining sensitivity of Plasmodium falciparum to pyronaridine].

OBJECTIVE: To establish an in vitro microtest for determining the sensitivity of Plasmodium falciparum to pyronaridine. METHODS: Pyronaridine-coated plate and culture medium which is easy to use in the field were prepared. P. falciparum parasites from in vitro continuous passage culture (FCC1/HN) were used for experimental tests in the laboratory. When they were proved stable and reliable through repeated determinations, field trials were made in Hainan and Yunnan Provinces during the malaria transmission season with blood samples from clinical falciparum malaria cases. A 4-week in vivo test was carried out as a control. RESULTS: The pyronaridine-coated plate and culture medium were proved to be stable. The effective period of pyronaridine-coated plate, the ampule sealed liquid culture medium and the bottled lyophilized culture medium, all stored at 4 degrees C was 6 months, 2 months and 2 years respectively. Through several years field determinations, the baseline data of pyronaridine-sensitivity of P. falciparum in the country were collected and the sensitivity of P. falciparum to pyronaridine was also revealed to have decreased gradually. The mean drug concentration for in vitro complete inhibition of schizont formation raised by 2-4 times although the clinical therapeutic efficacy of pyronaridine was still satisfactory at the present time. CONCLUSION: The developed in vitro microtest can be used for determination of the sensitivity of P. falciparum to pyronaridine, and it is more convenient and sensitive than the 4-week in vivo method.