A chromosome-level haplotype-resolved genome assembly of oriental tobacco budworm (Helicoverpa assulta).

Oriental tobacco budworm (Helicoverpa assulta) and cotton bollworm (Helicoverpa armigera) are two closely related species within the genus Helicoverpa. They have similar appearances and consistent damage patterns, often leading to confusion. However, the cotton bollworm is a typical polyphagous insect, while the oriental tobacco budworm belongs to the oligophagous insects. In this study, we used Nanopore, PacBio, and Illumina platforms to sequence the genome of H. assulta and used Hifiasm to create a haplotype-resolved draft genome. The Hi-C technique helped anchor 33 primary contigs to 32 chromosomes, including two sex chromosomes, Z and W. The final primary haploid genome assembly was approximately 415.19 Mb in length. BUSCO analysis revealed a high degree of completeness, with 99.0% gene coverage in this genome assembly. The repeat sequences constituted 38.39% of the genome assembly, and we annotated 17093 protein-coding genes. The high-quality genome assembly of the oriental tobacco budworm serves as a valuable genetic resource that enhances our comprehension of how they select hosts in a complex odour environment. It will also aid in developing an effective control policy.

Global, regional, and national burdens of early onset pancreatic cancer in adolescents and adults aged 15-49 years from 1990 to 2019 based on the Global Burden of Disease Study 2019: a cross-sectional study.

BACKGROUND: Early-onset pancreatic cancer (EOPC) in younger populations (age ≤50 years) is likely to be a more aggressive phenotype characterized by poor differentiation. The emerging analysis of the global burden of EOPC is limited and outdated. AIM: To systematically investigate the burden and trend of EOPC based on global populations. METHODS: In this systematic analysis based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, the authors present the number of cases, age-standardized rates (ASRs) per 100 000 population, and risk factors for 204 countries and territories. The average annual percentage changes (AAPCs) for the incidence, mortality, and disability-adjusted life-years (DALYs) of EOPC were calculated using joinpoint regression analysis. RESULTS: According to the GBD 2019 estimates, there were 36 852 new cases of EOPC and 32 004 related deaths. East Asia had the highest number of cases, with 11 401 incidences and 10 149 deaths. The ASRs were 0.94 per 100 000 individuals for incidence and 0.81 per 100 000 for mortality. From 1990 to 2019, the age-standardized incidence increased by 46.9%, mortality increased by 44.6%, and DALYs increased by 41.9% globally. In trend analysis, the global incidence (AAPC, 1.26), mortality (AAPC, 1.24), and DALYs (AAPC, 1.25) of EOPC showed an increasing pattern. The ASRs of incidence, mortality, and DALYs of EOPC in Africa, America, and Asia exhibited a continuous upward trend, while the trend in Europe was fluctuating. Asian males exhibited the fastest growth in incidence (AAPC, 2.15) and mortality (AAPC, 2.13), whereas males in the Americas experienced the slowest increase in new cases (AAPC, 0.72) and deaths (AAPC, 0.67). A certain proportion of EOPC DALYs were attributable to known risk factors: tobacco smoking (13.3%), high BMI, 5.6%, and high fasting plasma glucose 3.2%. Integrating the socio-demographic index (SDI), ASRs of incidence and mortality initially increased with rising SDI, reaching a peak in central Europe (1.5 per 100 000

Genome-wide analysis of long noncoding RNAs in response to salt stress in Nicotiana tabacum.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been shown to play important roles in the response of plants to various abiotic stresses, including drought, heat and salt stress. However, the identification and characterization of genome-wide salt-responsive lncRNAs in tobacco (Nicotiana tabacum L.) have been limited. Therefore, this study aimed to identify tobacco lncRNAs in roots and leaves in response to different durations of salt stress treatment. RESULTS: A total of 5,831 lncRNAs were discovered, with 2,428 classified as differentially expressed lncRNAs (DElncRNAs) in response to salt stress. Among these, only 214 DElncRNAs were shared between the 2,147 DElncRNAs in roots and the 495 DElncRNAs in leaves. KEGG pathway enrichment analysis revealed that these DElncRNAs were primarily associated with pathways involved in starch and sucrose metabolism in roots and cysteine and methionine metabolism pathway in leaves. Furthermore, weighted gene co-expression network analysis (WGCNA) identified 15 co-expression modules, with four modules strongly linked to salt stress across different treatment durations (MEsalmon, MElightgreen, MEgreenyellow and MEdarkred). Additionally, an lncRNA-miRNA-mRNA network was constructed, incorporating several known salt-associated miRNAs such as miR156, miR169 and miR396. CONCLUSIONS: This study enhances our understanding of the role of lncRNAs in the response of tobacco to salt stress. It provides valuable information on co-expression networks of lncRNA and mRNAs, as well as networks of lncRNAs-miRNAs-mRNAs. These findings identify important candidate lncRNAs that warrant further investigation in the study of plant-environment interactions.

Analysis of textbook outcomes for ampullary carcinoma patients following pancreaticoduodenectomy.

BACKGROUND: Textbook outcomes (TOs) have been used to assess the quality of surgical treatment for many digestive tumours but not ampullary carcinoma (AC). AIM: To discuss the factors associated with achieving a TO and further explore the prognostic value of a TO for AC patients undergoing curative pancreaticoduodenectomy (PD). METHODS: Patients who underwent PD at the China National Cancer Center between 1998 and 2020 were identified. A TO was defined by R0 resection, examination of ≥ 12 Lymph nodes, no prolonged hospitalization, no intensive care unit treatment, no postoperative complications, and no 30-day readmission or mortality. Cox regression analysis was used to identify the prognostic value of a TO for overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to identify predictors of a TO. The rate of a TO and of each indicator were compared in patients who underwent surgery before and after 2010. RESULTS: Ultimately, only 24.3% of 272 AC patients achieved a TO. A TO was independently associated with improved OS [hazard ratio (HR): 0.443, 95% confidence interval (95%CI): 0.276-0.711, P = 0.001] and RFS (HR: 0.379, 95%CI: 0.228-0.629, P < 0.001) in the Cox regression analysis. Factors independently associated with a TO included a year of surgery between 2010 and 2020 (OR: 4.549, 95%CI: 2.064-10.028, P < 0.001) and N1 stage disease (OR: 2.251, 95%CI: 1.023-4.954, P = 0.044). In addition, the TO rate was significantly higher in patients who underwent surgery after 2010 (P < 0.001) than in those who underwent surgery before 2010. CONCLUSION: Only approximately a quarter (24.3%) of AC patients achieved a TO following PD. A TO was independently related to favourable oncological outcomes in AC and should be considered as an outcome measure for the quality of surgery. Further multicentre research is warranted to better elucidate its impact.

Novel prognostic score based on the preoperative total bilirubin-albumin ratio and fibrinogen-albumin ratio in ampullary adenocarcinoma.

BACKGROUND: The preoperative total bilirubin-albumin ratio (TBAR) and fibrinogen-albumin ratio (FAR) have been proven to be valuable prognostic factors in various cancers. AIM: To detect the prognostic value of TBAR and FAR in ampullary adenocarcinoma (AC) patients who underwent curative pancreaticoduodenectomy. METHODS: AC patients who underwent curative pancreaticoduodenectomy in the National Cancer Center of China between 1998 and 2020 were retrospectively reviewed. The prognostic cutoff values of TBAR and FAR were determined through the best survival separation model. Then, a novel prognostic score combining TBAR and FAR was calculated and validated through the logistic regression analysis and Cox regression analysis. RESULTS: A total of 188 AC patients were enrolled in the current study. The best cutoff values of TBAR and FAR for predicting overall survival were 1.7943 and 0.1329, respectively. AC patients were divided into a TBAR-low group (score = 0) vs a TBAR-high group (score = 1) and a FAR-low group (score = 0) vs a FAR-high group (score = 1). The total score was calculated as a novel prognostic factor. Multivariable logistic regression analysis revealed that a high score was an independent protective factor for recurrence [score = 1 vs score = 0: Odds ratio (OR) = 0.517, P = 0.046; score = 2 vs score = 0 OR = 0.236, P = 0.038]. In addition, multivariable survival analysis also demonstrated that a high score was an independent protective factor in AC patients (score = 2 vs score = 0: Hazard ratio = 0.230, P = 0.046). CONCLUSION: A novel prognostic score based on preoperative TBAR and FAR has been demonstrated to have good predictive power in AC patients who underwent curative pancreaticoduodenectomy. However, more studies with larger samples are needed to validate this conclusion.

Equivalent Survival between Gastric Large-Cell Neuroendocrine Carcinoma and Gastric Small-Cell Neuroendocrine Carcinoma.

BACKGROUND: According to the 2019 World Health Organization (WHO) classification of gastric neuroendocrine neoplasms, gastric neuroendocrine carcinoma (GNEC) can be further divided into gastric large-cell neuroendocrine carcinoma (GLNEC) and gastric small-cell neuroendocrine carcinoma (GSNEC). Whether the prognoses of the two types have a discrepancy has long been disputed. METHOD: We collected patients diagnosed with GLNEC or GSNEC in the National Cancer Center of China between January 2000 and December 2020. The characteristics and survival outcomes were compared between the two groups. We further verified our conclusion using the SEER dataset. RESULTS: A total of 114 GNEC patients, including 82 patients with GLNEC and 32 patients with GSNEC, have completed treatment in our hospital. Clinicopathologic differences were not observed between patients with GSNEC and GLNEC concerning the sex, age, body mass index, Charlson Comorbidity Index, tumor location, tumor size, stage, treatment received, the expression of neuroendocrine markers (CD56, Chromogranin A, synaptophysin), and score on the Ki-67 index. The 1-year, 3-year, and 5-year overall survival rates of GLNEC and GSNEC were 89.0%, 60.5%, and 52.4%, and 93.8%, 56.3%, and 52.7%, which showed no statistically significant differences. This result was confirmed further by using the SEER dataset after the inverse probability of treatment weighting. CONCLUSIONS: Although with different cell morphology, the comparison of prognosis between the GLNEC and GSNEC has no significant statistical difference.

Impact of perioperative blood transfusion on oncological outcomes in ampullary carcinoma patients underwent pancreaticoduodenectomy.

BACKGROUND: The effect of perioperative blood transfusion (PBT) on the prognosis of ampullary carcinoma (AC) is still debated. AIM: To explore the impact of PBT on short-term safety and long-term survival in AC patients who underwent pancreaticoduodenectomy. METHODS: A total of 257 patients with AC who underwent pancreaticoduodenectomy between 1998 and 2020 in the Cancer Hospital, Chinese Academy of Medical Sciences, were retrospectively analyzed. We used Cox proportional hazard regression to identify prognostic factors of overall survival (OS) and recurrence-free survival (RFS) and the Kaplan-Meier method to analyze survival information. RESULTS: A total of 144 (56%) of 257 patients received PBT. The PBT group and nonperioperative blood transfusion group showed no significant differences in demographics. Patients who received transfusion had a comparable incidence of postoperative complications with patients who did not. Univariable and multivariable Cox proportional hazard regression analyses indicated that transfusion was not an independent predictor of OS or RFS. We performed Kaplan-Meier analysis according to subgroups of T stage, and subgroup analysis indicated that PBT might be associated with worse OS (P < 0.05) but not RFS in AC of stage T1. CONCLUSION: We found that PBT might be associated with decreased OS in early AC, but more validation is needed. The reasonable use of transfusion might be helpful to improve OS.

Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation: A case report and review of literature.

BACKGROUND: Both hepatoid adenocarcinoma of the stomach (HAS) and neuroendocrine differentiation (NED) are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes. HAS with NED is even rarer. CASE SUMMARY: Here, we report a 61-year-old man with HAS with NED, as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule. Distal gastrectomy was performed, and pathological examination led to the diagnosis of HAS with NED. However, liver metastases occurred 6 mo later despite adjuvant chemotherapy, and the patient died 27 mo postoperatively. CONCLUSION: We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases. We first report the detailed processes of the treatment and development of HAS with NED, providing an important reference for the clinical diagnosis and treatment of this condition.

Dissimilar survival and clinicopathological characteristics of mucinous adenocarcinoma located in pancreatic head and body/tail.

BACKGROUND: Growing evidence shows that pancreatic tumors in different anatomical locations have different characteristics, which have a significant impact on prognosis. However, no study has reported the differences between pancreatic mucinous adenocarcinoma (PMAC) in the head vs the body/tail of the pancreas. AIM: To investigate the differences in survival and clinicopathological characteristics between PMAC in the head and body/tail of pancreas. METHODS: A total of 2058 PMAC patients from the Surveillance, Epidemiology, and End Results database diagnosed between 1992 and 2017 were retrospectively reviewed. We divided the patients who met the inclusion criteria into pancreatic head group (PHG) and pancreatic body/tail group (PBTG). The relationship between two groups and risk of invasive factors was identified using logistic regression analysis. Kaplan-Meier analysis and Cox regression analysis were conducted to compare the overall survival (OS) and cancer-specific survival (CSS) of two patient groups. RESULTS: In total, 271 PMAC patients were included in the study. The 1-year, 3-year, and 5-year OS rates of these patients were 51.6%, 23.5%, and 13.6%, respectively. The 1-year, 3-year, and 5-year CSS rates were 53.2%, 26.2%, and 17.4%, respectively. The median OS of PHG patients was longer than that of PBTG patients (18 vs 7.5 mo, P < 0.001). Compared to PHG patients, PBTG patients had a greater risk of metastases [odds ratio (OR) = 2.747, 95% confidence interval (CI): 1.628-4.636, P < 0.001] and higher staging (OR = 3.204, 95% CI: 1.895-5.415, P < 0.001). Survival analysis revealed that age < 65 years, male sex, low grade (G1-G2), low stage, systemic therapy, and PMAC located at the pancreatic head led to longer OS and CSS (all P < 0.05). The location of PMAC was an independent prognostic factor for CSS [hazard ratio (HR) = 0.7, 95%CI: 0.52-0.94, P = 0.017]. Further analysis demonstrated that OS and CSS of PHG were significantly better than PBTG in advanced stage (stage III-IV). CONCLUSION: Compared to the pancreatic body/tail, PMAC located in the pancreatic head has better survival and favorable clinicopathological characteristics.

Exploration of the lymphadenectomy strategy for elderly pancreatic ductal adenocarcinoma patients undergoing curative-intent resection.

There has been a long-standing controversy regarding the number of lymph nodes (LNs) examined intraoperatively for accurate lymphatic staging and significantly better survival of patients with pancreatic ductal adenocarcinoma (PDAC), and no consensus has been reached for the elderly with the age of over 75 years. Given these, the present study aims to investigate the appropriate number of examined lymph nodes (ELNs) for elderly patients mentioned above. In this study, population-based data on 20,125 patients in 2000 to 2019 from the Surveillance, Epidemiology, and End Results database were reviewed retrospectively. The eighth edition staging system of the American Joint Committee on Cancer (AJCC) was applied. Propensity score matching (PSM) was performed to reduce the effects of multiple biases. By using binomial probability law and maximally selected rank statistics, the minimum number of ELN (MNELN) for accurate nodal involvement assessment and optimal ELN number for significantly better survival were calculated, respectively. In addition, Kaplan-Meier curves and Cox proportional hazard regression models were constructed for further survival analysis. As a result, 6623 patients were enrolled in total in the study. Elderly patients had fewer lymph node metastases and a smaller lymph node ratio (LNR) (all P<0.05). However, poorer overall survival (OS) and cancer-specific survival (CSS) of elderly patients were observed in each pN stage (all P<0.05), except for CSS in N2. The proportions of N2 and N0 stages increased and decreased respectively with increasing number of ELN significantly. MNELN for accurate nodal assessment was 19 according to binomial probability law, and the optimal ELN number for significantly better survival was 17. Additionally, the number of ELN (<17 or ≥17) was also considered a strong prognostic predictor for elderly PDAC patients (≥75 years) in the Cox proportional hazard regression model (Overall survival: hazard ratio [HR]=0.74, 95% confidence interval [CI]: 0.65-0.83, P<0.001; Cancer-specific survival: HR=0.75, 95% CI: 0.66-0.85, P<0.001). In conclusion, extended lymphadenectomy is suitable for elderly PDAC patients undergoing curative-intent surgery owing to an accurate assessment of nodal status and improved long-term prognosis. However, a random, prospective clinical trial is warranted before the recommendation of extended lymphadenectomy for the elderly.

Anti-apoptotic protein BCL-XL as a therapeutic vulnerability in gastric cancer.

BACKGROUND: New therapeutic targets are needed to improve the outcomes for gastric cancer (GC) patients with advanced disease. Evasion of programmed cell death (apoptosis) is a hallmark of cancer cells and direct induction of apoptosis by targeting the pro-survival BCL2 family proteins represents a promising therapeutic strategy for cancer treatment. Therefore, understanding the molecular mechanisms underpinning cancer cell survival could provide a molecular basis for potential therapeutic interventions. METHOD: Here we explored the role of BCL2L1 and the encoded anti-apoptotic BCL-XL in GC. Using Droplet Digital PCR (ddPCR) technology to investigate the DNA amplification of BCL2L1 in GC samples and GC cell lines, the sensitivity of GC cell lines to selective BCL-XL inhibitors A1155463 and A1331852, pan-inhibitor ABT-263, and VHL-based PROTAC-BCL-XL was analyzed using (CellTiter-Glo) CTG assay in vitro. Western Blot (WB) was used to detect the protein expression of BCL2 family members in GC cell lines and the manner in which PROTAC-BCL-XL kills GC cells. Co-immunoprecipitation (Co-IP) was used to investigate the mechanism of A1331852 and ABT-263 kills GC cell lines. DDPCR, WB, and real-time PCR (RTPCR) were used to investigate the correlation between DNA, RNA, protein levels, and drug activity. RESULTS: The functional assay showed that a subset of GC cell lines relies on BCL-XL for survival. In gastric cancer cell lines, BCL-XL inhibitors A1155463 and A1331852 are more sensitive than the pan BCL2 family inhibitor ABT-263, indicating that ABT-263 is not an optimal inhibitor of BCL-XL. VHL-based PROTAC-BCL-XL DT2216 appears to be active in GC cells. DT2216 induces apoptosis of gastric cancer cells in a time- and dose-dependent manner through the proteasome pathway. Statistical analysis showed that the BCL-XL protein level predicts the response of GC cells to BCL-XL targeting therapy and BCL2L1 gene CNVs do not reliably predict BCL-XL expression. CONCLUSION: We identified BCL-XL as a promising therapeutic target in a subset of GC cases with high levels of BCL-XL protein expression. Functionally, we demonstrated that both selective BCL-XL inhibitors and VHL-based PROTAC BCL-XL can potently kill GC cells that are reliant on BCL-XL for survival. However, we found that BCL2L1 copy number variations (CNVs) cannot reliably predict BCL-XL expression, but the BCL-XL protein level serves as a useful biomarker for predicting the sensitivity of GC cells to BCL-XL-targeting compounds. Taken together, our study pinpointed BCL-XL as potential druggable target for specific subsets of GC.

CD93 serves as a potential biomarker of gastric cancer and correlates with the tumor microenvironment.

BACKGROUND: The tumor microenvironment (TME) plays an important role in the growth and expansion of gastric cancer (GC). Studies have identified that CD93 is involved in abnormal tumor angiogenesis, which may be related to the regulation of the TME. AIM: To determine the role of CD93 in GC. METHODS: Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas. Additionally, RNA-seq data sets from Gene Expression Omnibus (GSE118916, GSE52138, GSE79973, GSE19826, and GSE84433) were applied to validate the results. We performed the immune infiltration analyses using ESTIMATE, CIBERSORT, and ssGSEA. Furthermore, weighted gene co-expression network analysis (WGCNA) was conducted to identify the immune-related genes. RESULTS: Compared to normal tissues, CD93 significantly enriched in tumor tissues (t = 4.669, 95%CI: 0.342-0.863, P < 0.001). Higher expression of CD93 was significantly associated with shorter overall survival (hazard ratio = 1.62, 95%CI: 1.09-2.4, P = 0.017), less proportion of CD8 T and activated natural killer cells in the TME (P < 0.05), and lower tumor mutation burden (t = 4.131, 95%CI: 0.721-0.256, P < 0.001). Genes co-expressed with CD93 were mainly enriched in angiogenesis. Moreover, 11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA. CONCLUSION: CD93 is a novel prognostic and diagnostic biomarker for GC, that is closely related to the immune infiltration in the TME. Although this retrospective study was a comprehensive analysis, the prospective cohort studies are preferred to further confirm these conclusions.

Survival benefit of younger gastric cancer patients in China and the United States: A comparative study.

BACKGROUND: The impact of racial and regional disparity on younger patients with gastric cancer (GC) remains unclear. AIM: To investigate the clinicopathological characteristics, prognostic nomogram, and biological analysis of younger GC patients in China and the United States. METHODS: From 2000 to 2018, GC patients aged less than 40 years were enrolled from the China National Cancer Center and the Surveillance Epidemiology and End Results database. Biological analysis was performed based on the Gene Expression Omnibus database. Survival analysis was conducted via Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: A total of 6098 younger GC patients were selected from 2000 to 2018, of which 1159 were enrolled in the China National Cancer Center, and 4939 were collected from the Surveillance Epidemiology and End Results database. Compared with the United States group, younger patients in China revealed better survival outcomes (P < 0.01). For race/ethnicity, younger Chinese cases also enjoyed a better prognosis than that in White and Black datasets (P < 0.01). After stratification by pathological Tumor-Node-Metastasis (pTNM) stage, a survival advantage was observed in China with pathological stage I, III, and IV (all P < 0.01), whereas younger GC patients with stage II showed no difference (P = 0.16). In multivariate analysis, predictors in China involved period of diagnosis, linitis plastica, and pTNM stage, while race, diagnostic period, sex, location, differentiation, linitis plastica, signet ring cell, pTNM stage, surgery, and chemotherapy were confirmed in the United States group. Prognostic nomograms for younger patients were established, with the area under the curve of 0.786 in the China group and of 0.842 in the United States group. Moreover, three gene expression profiles (GSE27342, GSE51105, and GSE38749) were enrolled in further biological analysis, and distinctive molecular characteristics were identified in younger GC patients among different regions. CONCLUSION: Except for younger cases with pTNM stage II, a survival advantage was observed in the China group with pathological stage I, III, and IV compared to the United States group, which might be partly due to differences in surgical approaches and the improvement of the cancer screening in China. The nomogram model provided an insightful and applicable tool to evaluate the prognosis of younger patients in China and the United States. Furthermore, biological analysis of younger patients was performed among different regions, which might partly explain the histopathological behavior and survival disparity in the subpopulations.

At least 16 lymph nodes are recommended to examine during pancreaticoduodenectomy in ampullary adenocarcinoma.

The minimum number of lymph nodes to be examined during pancreaticoduodenectomy (PD) for patients with ampullary adenocarcinoma (AC) is still debatable due to limited clinical data. Therefore, here we explored the relationship between the number of examined lymph node (ELN) and the current N staging (American Joint Committee on Cancer staging system, AJCC, 8 edition) after PD for AC as well as determined the minimum number of examined lymph nodes (MNELN) to ensure the accurate detection of nodal involvement. Patients underwent PD for AC in the National Cancer Center cohort of China (NCC cohort of China) from 1998 to 2020 and in the Surveillance, Epidemiology, and End Results database (SEER database) from 2010 to 2018 were retrospectively reviewed, and a total of 452 eligible patients were included in this study. The MNELN was evaluated by binomial probability law and best survival separation methods. Furthermore, the cut-off value of MNELN was validated in the NCC cohort of China using Least Absolute Shrinkage and Selection Operator (LASSO) regression. Our analysis indicated that the median number of ELN was 14, and the number of ELN was positively correlated with N stage. The MNELN was 16, whereas the best survival separation of ELN was 38 in node-positive patients and 3 in node-negative patients. In the validation cohort, the number of 16 ELNs was identified as a predictive variable for lymph node metastasis with nonzero coefficients in the LASSO-logistic regression model. Together, we concluded that a greater number of ELN was associated with more accurate nodal status assessment in PD for AC patients. A minimum of 16 lymph nodes were required to during PD in AC patients.

Does Surgical Resection Significantly Prolong the Long-Term Survival of Patients with Oligometastatic Pancreatic Ductal Adenocarcinoma? A Cross-Sectional Study Based on 18 Registries.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a type of lethal gastrointestinal malignancy. It is mainly discovered at, and diagnosed with, an advanced stage of metastasis. As the only potentially curative treatment for PDAC, surgical resection has an uncertain impact on the survival of these patients. As such, we aimed to investigate if patients with metastatic PDAC (mPDAC) benefit from surgery. Methods: Patients with pancreatic cancer in 18 registries of the Surveillance, Epidemiology, and End Results database between 2000 and 2018 were reviewed retrospectively. According to the American Joint Committee on Cancer (AJCC), the eighth edition staging system was utilized. Propensity score matching was applied to strengthen the comparability of the study. The impact of surgery on survival was evaluated by restricted mean survival time (RMST) and Kaplan−Meier analysis. Results: A total of 210 well-matched mPDAC patients were included in the study. The 1 year, 3 year, and 5 year overall survival (OS) of patients undergoing surgery was 34.3%, 15.2%, and 11.0%, respectively. The 1 year, 3 year, and 5 year cancer-specific survival (CSS) of these patients was 36.1%, 19.7%, and 14.2%, respectively. RMST analysis revealed that mPDAC patients with surgery had better OS and CSS than those without (OS: 9.49 months vs. 6.45 months, p < 0.01; CSS: 9.76 months vs. 6.54 months, p < 0.01). Nevertheless, subgroup analysis demonstrated that such statistical significance especially existed in oligometastatic PDAC patients, which refers to those metastases that were limited in number and concentrated to a single organ in this study. Additionally, surgery was identified as a significant predictor for the long-term prognosis of patients (OS: [HR, hazard ratio] = 0.48, 95% CI: 0.36−0.65, p < 0.001; CSS: HR = 0.45, 95% CI: 0.33−0.63, p < 0.001). Lastly, a nomogram was established to predict whether an individual was suitable for surgical treatment in this study. Conclusions: Surgical resection significantly prolonged the long-term prognosis of oligometastatic PDAC patients. Such insights might broaden the management of patients with mPDAC to a large extent. However, a prospective clinical trial should be conducted before a recommendation of surgery in these patients.

Metagenomic insights into the changes in the rhizosphere microbial community caused by the root-knot nematode Meloidogyne incognita in tobacco.

Root-knot nematode (RKN) disease is a destructive soil disease that affects crop health and causes huge losses in crop production. To explore the relationships between soil environments, rhizobacterial communities, and plant health, rhizosphere bacterial communities were analyzed using metagenomic sequencing in tobacco samples with different grades of RKN disease. The results showed that the community structure and function of the plant rhizosphere were significantly correlated to the RKN disease. RKN density and urease content were key factors affecting the rhizosphere bacterial community. Urease accelerated the catabolism of urea and led to the production of high concentrations of ammonia, which directly suppressed the development of RKNs or by improving the nutritional and growth status of microorganisms that were antagonistic to RKNs. Further experiments showed that the suppression role of ammonia should be attributed to the direct inhibition of NH3. The bacterial members that were positively correlated with RKN density, contained many plant cell wall degrading enzymes, which might destroy plant cell walls and promote the colonization of RKN in tobacco roots. The analysis of metatranscriptome and metabolism demonstrated the role of these cell wall degrading enzymes. This study offers a comprehensive insight into the relationships between RKNs, bacteria, and soil environmental factors and provides new ideas for the biological control of RKNs.

Accurate identification of traumatic lung injury (TLI) by ATR-FTIR spectroscopy combined with chemometrics.

Traumatic lung injury (TLI), which is a common mechanical injury, is receiving increasing attention because of its serious hazards. In forensic practices, accurately identifying TLI is of great importance for investigations and case trials. The main goal of this research was to identify TLI utilizing attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy in combination with chemometrics. The macroscopic appearance of lung tissue showed that identifying TLI in lung tissue at the decomposition stage is not feasible by only visualization, and significant pulmonary hypostasis was observed in the lungs regardless of whether the lung tissue was injured. Average spectra and principal component analysis (PCA) suggested that the biochemical difference between injured lung tissue samples from the TLI group and noninjured lung tissue samples from the negative control group was mainly attributed to the different structures and contents of proteins. Partial least squares discriminant analysis (PLS-DA) was then utilized to identify TLI with an accuracy of 96.4% and 98.6% based on the training set and the test set, respectively. Next, we focused on samples that were misclassified in the model and proposed that the misclassification could be caused by the pulmonary hypostasis effect. Therefore, two additional PCA and PLS-DA models were created to identify the pulmonary hypostatic areas between the TLI group and the negative control group and the nonpulmonary hypostatic areas between the TLI group and the negative control group. The PCA results indicated that the biochemical difference between the two groups was still associated with proteins, and the two PLS-DA models achieved 100% accuracy based on both the training and test sets. This result indicated that when pulmonary hypostasis was considered and the lung tissue was divided into pulmonary hypostatic areas and nonpulmonary hypostatic areas for separate comparisons, TLI identification was achieved with a greater accuracy than that obtained when the two areas were combined. This research confirms that the combined application of ATR-FTIR spectroscopy and chemometrics can be utilized to accurately identify TLI.

Transcription factor NtWRKY33a modulates the biosynthesis of polyphenols by targeting NtMYB4 and NtHCT genes in tobacco.

There are abundant polyphenols in tobacco leaves mainly including chlorogenic acid (CGA), rutin, and scopoletin, which not only influence plant growth, development, and environmental adaptation, but also have a great impact on the industrial utilization of tobacco leaves. Few transcription factors regulating the biosynthesis of polyphenols have been identified in tobacco so far. In this study, two NtWRKY33 genes were identified from N. tabacum genome. NtWRKY33a showed higher transcriptional activity than NtWRKY33b, and encoded a nuclear localized protein. Overexpression and knock-out of NtWRKY33a gene revealed that NtWRKY33a inhibited the accumulation of rutin, scopoletin, and total polyphenols, but meanwhile promoted the biosynthesis of CGA. Chromatin immunoprecipitation and Dual-Luc assays indicated that NtWRKY33a could directly bind to the promoters of NtMYB4 and NtHCT, and thus induced the transcription of these two genes. The contents of polyphenols in ntwrky33a, ntmy4, and ntwrky33a/ntmyb4 mutants further confirmed that the repression of NtWRKY33a on the biosynthesis of rutin, scopoletin, and total polyphenols depends on the activity of NtMYB4. Moreover, the promotion of NtHCT by NtWRKY33a modulates the distribution of metabolism flux into the synthesis of CGA. Ectopic expression of NtWRKY33a inhibit the expression of NtSAUR14, NtSAUR59, NtSAUR66, NtIAA4, NtIAA17, and NtIAA19 genes, indicating that NtWRKY33a might be involved in the regulation of plant auxin response. Our study revealed new functions of NtWRKY33a in regulating the synthesis of polyphenols, and provided a promising target for manipulating polyphenols contents in tobacco.

Prognostic and Immunological Significance of Rhomboid Domain Containing Protein 1 in Multiple Primary Cancers.

BACKGROUND: RHBDD1 is an intramembrane serine protease of the rhomboid superfamily that regulates diverse physiological and pathological processes. However, the relationship between RHBDD1 expression, tumor-infiltrating immune cells (TIICs), and cancer prognosis remains unclear. OBJECTIVE: We comprehensively analyzed the prognostic and immunological significance of RHBDD1 in multiple primary cancers. METHODS: RHBDD1 expression was investigated using Oncomine, TIMER, and UALCAN databases, after which the clinical prognostic value of RHBDD1 was assessed with online public databases. In addition, we explored the correlation between RHBDD1 and TIICs by TIMER and GEPIA and investigated the relationship between RHBDD1 expression and chemokines in cancers by TIMER. RESULTS: In general, compared to that in adjacent normal tissue, lower expression of RHBDD1 was found in various cancers and was correlated to pathological stages. Although RHBDD1 showed a protective effect on multiple solid tumors, a high expression level of RHBDD1 was detrimental to the survival of stomach adenocarcinoma patients. RHBDD1 was positively correlated to immune infiltration levels in various cancers, including lung, breast, ovarian, and gastric cancer. Furthermore, gene markers of TIICs, such as tumor-associated macrophages (TAMs), dendritic cells (DCs), and regulatory T cells, were also correlated to RHBDD1 expression. In addition, the RHBDD1 expression level was positively correlated to multiple chemokines in cancers, which could recruit diverse immune cells at the tumor site. CONCLUSIONS: RHBDD1, which correlates with immune infiltration, can be used as a potential prognostic biomarker in multiple primary cancers. Specifically, RHBDD1 expression potentially contributes to the recruitment of TAMs and DCs and the regulation of T cell functions in cancers.

Effects of Serum Lipids on the Long-Term Prognosis of Ampullary Adenocarcinoma Patients after Curative Pancreatoduodenectomy.

BACKGROUND: Serum lipids (SLs), the prominent indicators of lipid metabolism, produce an intricate impact on proliferation, invasion, and metastasis of cancer cells. However, the effects of serum lipids on the prognosis of ampullary adenocarcinoma (AC) have not been investigated. METHODS: Patients with AC in the National Cancer Center of China between January 1998 and December 2020 were retrospectively reviewed. Survival analysis for overall survival (OS, Time from operation to death) and recurrence-free survival (RFS, Time from operation to first-time recurrence) was performed using Kaplan-Meier analysis and Cox proportional hazards models. RESULTS: A total of 232 AC patients were enrolled into the study. SLs levels were significantly lower in patients with vascular invasion compared to those without (all p < 0.05). The 1-year, 3-year, and 5-year OS rates for AC patients were 86.1%, 64.1%, and 47.6% and 75.8%, 54.8%, and 46.5% for RFS. Biliary/pancreatic fistula (31.9%) and chemotherapy (81.4%) were the majority of postoperative complications and adjuvant therapy, respectively. According to Cox analysis, preoperative LDL-C was an independent prognostic factor for RFS (HR = 0.43, 95% CI: 0.21-0.85, p = 0.015), whereas no statistical significance existed in the analysis of HDL-C, TC, and TG. CONCLUSIONS: High levels of preoperative LDL-C is a significant predictor of prolonged prognosis in AC patients, which was also observed to be a protective factor to reduce vascular invasion.