Combined large cell neuroendocrine carcinoma, lung adenocarcinoma, and squamous cell carcinoma: a case report and review of the literature.

BACKGROUND: Combined large cell neuroendocrine carcinoma (C-LCNEC) has a poor prognosis and there is no consensus about the treatment regimen for both LCNEC and C-LCNEC patients. CASE PRESENTATION: The patient was a 47-year-old female who received surgical resection. The postoperative histology and staging of the tumor suggested C-LCNEC with adenocarcinoma and squamous cell carcinoma and T2aN0M0 stage IB. Next-generation sequencing test showed KIF5B/RET fusion mutation without EGFR, ALK, RB1, and TP53 alterations. Adjuvant chemotherapy with 4-cycle docetaxel plus carboplatin was given and brain metastasis occurred after 10 months. CONCLUSIONS: C-LCNEC with adenocarcinoma and squamous cell carcinoma is rare and highly aggressive cancer. Surgical resection and adjuvant chemotherapy with SCLC regimen may improve the disease-free survival and overall survival. The accumulation of similar cases will clarify the profile and management of the disease.

Cognitive adverse events in patients with lung cancer treated with checkpoint inhibitor monotherapy: a propensity score-matched analysis.

Background: Cancer-related cognitive decline is a serious problem in long-term survival but no pivotal study has investigated whether checkpoint inhibitors (ICI) may be associated with cognitive adverse events. Methods: This propensity score-matched analysis recruited non-small cell lung cancer (NSCLC) patients prescribed with or without ICI monotherapy from three Chinese tertiary hospitals. Patients were excluded from study who developed brain metastasis or had disorders severely affecting cognitive abilities. Primary outcomes were changes in neuropsychological battery test (NBT) at baseline, 6- and 12-month sessions, and any NBT score changes that exceeded 3∗SD of baseline scores would be marked as objective cognitive adverse events (CoAE). Secondary endpoint was the 20-item Perceived Cognitive Impairment (PCI) sub-scale score change in Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, administered at baseline, 3-, 6-, 9-, 12-, and 15-month follow-up session. Per-protocol ICI and control arms were matched with propensity scores that incorporated baseline variables to compare both NBT and PCI assessment results. Patients participating in PCI assessments were analysed in intention-to-treat analysis. Kaplan-Meier survival curves with log-rank tests were adopted to analyse incidence of perceived cognitive decline events (PCDE). Findings: Between March 12, 2020, and March 28, 2021, 908 participants were enrolled. Compared to control, 3 of 4 subtest of NBT scores in ICI arm showed significant cognitive decline in 6- and 12-month sessions, in which Trail Making Test score change (13.56 ± 11.73) reached threshold of cognitive deficit diagnosis in the 12-month session. In 1:1 matched 292 pairs from 908 patients, PCI score changes in ICI arms were -4.26 ± 8.54 (3rd month), -4.72 ± 11.83 (6th month), -6.16 ± 15.41 (9th month), -6.07 ± 15.71 (12th month), and -7.96 ± 13.97 (15th month). The scores were significantly lower than control arm in 3-, 6-, and 12-session follow-up. The result was validated after adjusting quality of life scores and in intention-to-treat analysis. Mean PCI change exceeded 1/2 SD of baseline PCI score (5.81) in 9-, 12-, and 15-month sessions in ICI arm, but not in control arm. PCDE incidence/prevalence was significantly higher in ICI arm (incidence 26.4% vs. 5.1%, and prevalence 16.2% vs. 1.7%). Immune-related adverse events related to incidence of PCDE after adjusting for baseline variables. Interpretation: ICI monotherapy seemed to relate to higher cognitive decline represented by score changes and incidence/prevalence rates. The decline deteriorated as treatment progressed, and immune-related adverse events seemed to be associated with higher cognitive adverse events incidence in the ICI treatment. Funding: The Fellowship of China Postdoctoral Science Foundation and National Natural Science Foundation of China Youth Science Fund Project.

circDYRK1A tethers biological behaviors of gastric carcinoma using novel bioinformatics analysis and experimental validations.

Gastric cancer has been one of the wide public health burdens with its high morbidity and mortality over several decades. As the unconventional modules among RNA families, circular RNAs present their blazing biological effects during gastric carcinogenesis. Though diverse hypothetical mechanisms were reported, further tests were necessitated for authentication. Herein, this study pinpointed a representative circDYRK1A which screened from vast amounts of public data sets using surprisingly novel bioinformatics approaches together with validations from the in vitro findings and then concluded that circDYRK1A tethered the biological behavior and swayed the clinicopathological features with gastric cancer patients thus providing an in-depth awareness for gastric carcinoma.

Wider indications and more efficient drug delivery: A bibliometric analysis and visualization of photodynamic therapy in skin cancer.

BACKGROUND: Photodynamic therapy (PDT) has been widely accepted in keratocyte carcinoma and an increasing number of literatures concerning PDT in skin cancer is published. But a detailed examination of publication patterns of PDT in skin cancer has not yet been carried out. METHODS: Bibliographies were retrieved from Web of Science Core Collection restricted the publication date from January 1, 1985 to December 31, 2021. The search terms were photodynamic therapy and skin cancer. Visualization analysis and statistical analysis were performed by VOSviewer (Version 1.6.13), R software (Version 4.1.2) and Scimago Graphica (Version 1.0.15). RESULTS: 3248 documents were selected for analysis. The results showed that the number of annual publications related to PDT in skin cancer was gradually increased and would continue to increase in the future. The results illustrated that "melanoma", "nanoparticles", "drug-delivery", "mechanism", "delivery" and "in-vitro" are newly occurred topics. The most prolific country was the United States and the most productive institution was the University of Sao Paulo in Brazil. German researcher Szeimies RM published the most papers related to PDT in skin cancer. British Journal of Dermatology was the most popular journal in this field. CONCLUSION: The topic that PDT in skin cancer is a heated issue. Our study revealed the bibliometric result of the field, which might provide the prospects for further research. We recommend future investigations focusing on PDT in treating melanoma, innovation of photosensitizer, improvement of drug delivery and the mechanism of PDT in skin cancer.

Vascular dementia: A microglia's perspective.

Vascular dementia (VaD) is a second most common form of age-related dementia. It is characterized by cognitive impairment associated with vascular pathology, symptoms mainly caused by cerebral damage due to inadequate blood flow to the brain. The pathogenesis of VaD is complex, and a growing body of literature emphasizes on the involvement of microglia in disease development and progression. Here, we review the current knowledge on the role of microglia in regulating neuroinflammation under the pathogenesis of VaD. The commonly used animal and cell models for understanding the disease pathogenesis were summarized. The mechanisms by which microglia contribute to VaD are multifactorial, and we specifically focus on some of the predominant functions of microglia, including chemotaxis, secretory property, phagocytosis, and its crosstalk with other neurovascular unit cells. Finally, potential therapeutic strategies targeting microglia-modulated neuroinflammation are discussed.

Pyroptosis is related to immune infiltration and predictive for survival of colon adenocarcinoma patients.

Pyroptosis is a novel type of programmed cell death, initiated by inflammasome. Pyroptosis inhibits the development and metastasis of colon cancer and is associated with patients' prognosis. However, how the pyroptosis-related genes predict the survival of patients is still unclear. In the study, colon adenocarcinoma (COAD) patients were divided into two groups according to the expression of pyroptosis-related regulators through consensus clustering. DEGs between two clusters were analyzed by using COX and Lasso regression. Then, regression coefficients in Lasso were used to calculate the risk score for every patient. Patients were classified into two types: low- and high-risk group according to their risk score. The difference of immune microenvironment infiltration and clinicopathological characteristics between subgroups was performed. Moreover, the nomogram model was built on the bases of risk model and clinicopathological factors. The TCGA-COAD cohort and GEO cohort were used as training and validating set respectively. 398 COAD patients in TCGA training set were identified as two regulation patterns via unsupervised clustering method. Patients in cluster 2 showed better prognosis (P = 0.002). Through differentiated expression analysis, COX and Lasso regression, a 5-gene prognostic risk model was constructed. This risk model was significantly associated with OS (HR: 2.088, 95% CI: 1.183-3.688, P = 0.011), validated in GEO set (HR:1.344, 95%CI: 1.061-1.704, P = 0.014), and patients with low risk had better prognosis (P < 0.001 in TCGA; P = 0.038 in GEO). Through ROC analysis, it can be found that this model presented better predictive accuracy for long-term survival. Clinical analyses demonstrated that high-risk group had more advanced N stage, higher risk of metastasis and later pathological stage. Immune-related analysis illustrated that low-risk group had more immune cell infiltration and more activated immune pathways. The pyroptosis-related risk model can be predictive for the survival of COAD patients. That patients with higher risk had poorer prognosis was associated with more advanced tumor stage and higher risk of metastasis, and resulted from highly activated pro-tumor pathways and inhibited immune system and poorer integrity of intestinal epithelial. This study proved the relationship between pyroptosis and immune, which offered basis for future studies.

Effect of Chemoradiotherapy on the Survival of Resectable Gastric Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Adjuvant chemotherapy (CT) and chemoradiotherapy (CRT) after surgery are necessary to reduce the risk of metastasis and recurrence for resectable gastric cancer (GC) patients. Adjuvant CT and CRT have been proven to significantly improve the prognosis for GC patients, when compared with surgery only. However, it is still unclear whether radiotherapy offers additional survival benefits to advanced gastric cancer (AGC) patients. METHODS: PubMed, Cochrane Library, and Embase databases were systematically searched for eligible studies that compared survival benefits between CRT and CT. The endpoints of this meta-analysis were measured as HR for OS or DFS and 95% CI using fixed- or random-effect models. Additionally, side effects, completed rate, and metastatic risk, were calculated as OR. Subgroup analyses according to clinicopathological factors were presented. RESULTS: A total of 28 eligible studies involving 20,220 patients were included in our study. Of these, 17 studies evaluated the survival benefits of additional radiotherapy on overall survival (OS) of gastric cancer patients, ten reported the impact of CRT on disease-free survival (DFS), and 26 studies showed long-term survival rate. The pooled results were significant (HR for OS 0.84, 95% CI 0.71-0.99; HR for DFS 0.76, 95% CI 0.66-0.89). The subgroup analysis showed that adjuvant CRT increased OS for patients without preoperative treatment; showed similar nausea/vomiting, but an increased risk of neutropenia; reduced the risk of locoregional recurrence; failed to improve OS for lymph node (LN)-positive GC patients; and significantly improved prognosis for R1-treated patients. Of note, DFS was improved in all the subgroups via decreasing the locoregional recurrence. CONCLUSION: Compared with CT, adjuvant CRT can improve survival for advanced gastric cancer patients, with similar nausea/vomiting, but increased risk of neutropenia. Patients without preoperative treatment or with positive surgical margins should be strongly recommended to undergo CRT. Treatment regimens should be carefully decided by doctors based on patients' tolerance, physical status, and reaction to treatment. Moreover, CRT improves the DFS for patients regardless of subgroups, because it significantly reduced the risk of locoregional recurrence.

Preoperative Ultrasound-Guided Incisional Biopsy Enhances the Pathological Accuracy of Incisional Biopsy of Cutaneous Melanoma: A Prospective Clinical Trial in Chinese Patients.

OBJECTIVES: To assess the feasibility of preoperative ultrasound (US)-guided incisional biopsy through a prospective controlled clinical trial. METHODS: This was a prospective, double-arm, single-center study of Chinese patients. Thirty patients were enrolled in the study. Fourteen patients received incisional biopsies for which the choice of biopsy area relied on a clinical evaluation, and 16 patients received incisional biopsies for which the choice of biopsy area relied on a US-guided evaluation. The following procedure was used in the US-guided incisional biopsy group: 1) clinical and dermoscopic evaluation of skin lesions; 2) US examination; 3) incisional biopsy; 4) surgical excision; and 5) histopathological examination. The same procedure was used in the non-US-guided group except without US examination. RESULTS: In the non-US-guided group, the mean tumor thicknesses obtained from incisional biopsy and postoperative histopathological examination were 2.1 and 4.1 mm, respectively. Seven melanomas were underestimated by incisional biopsy, resulting in margins narrower than currently recommended. In the US-guided group, the mean tumor thicknesses obtained from US, incisional biopsy, and postoperative histopathological examination were 3.4, 2.9, and 2.7 mm, respectively. In only 3 melanomas was the tumor thickness of the incisional biopsy less than that of the postoperative histopathological examination, demonstrating that US-guided biopsy obtains the maximum thickness area. CONCLUSIONS: Preoperative US-guided incisional biopsy can enhance the pathological accuracy of incisional biopsy, which may allow us to better perform surgical excision with safe peripheral surgical margins.

Predicting functional circular RNA-based competitive endogenous RNA network in gastric carcinoma using novel bioinformatics analysis.

Gastric cancer (GC) remains one of the most prevalent types of malignancies worldwide, and also one of the most reported lethal tumor-related diseases. Circular RNAs (circRNAs) have been certified to be trapped in multiple aspects of GC pathogenesis. Yet, the mechanism of this regulation is mostly undefined. This research is designed to discover the vital circRNA-microRNA (miRNA)-messenger RNA (mRNA) regulatory network in GC. Expression profiles with diverse levels including circRNAs, miRNAs, and mRNAs were all determined using microarray public datasets from Gene Expression Ominous (GEO). The differential circRNAs expressions were recognized against the published robust rank aggregation algorithm. Besides, a circRNA-based competitive endogenous RNA (ceRNA) interaction network was visualized via Cytoscape software (version 3.8.0). Functional and pathway enrichment analysis associated with differentially expressed targeted mRNAs were conducted using Cytoscape and an online bioinformatics database. Furthermore, an interconnected protein-protein interaction association network which consisted of 51 mRNAs was predicted, and hub genes were screened using STRING and CytoHubba. Then, several hub genes were chosen to explore their expression associated with survival rate and clinical stage in GEPIA and Kaplan-Meier Plotter databases. Finally, a carefully designed circRNA-related ceRNA regulatory subnetwork including four circRNAs, six miRNAs, and eight key hub genes was structured using the online bioinformatics tool.

Differentiated/undifferentiated mixed type is a prognostic factor for T2/T3 gastric cancer patients.

OBJECTIVES: This work aimed to find the association of mixed-type histology and prognosis of T2/T3 GC patients. METHODS: Eligible T2/T3 gastric cancer patients at our institution were identified. The histological types and risk factors affecting OS were examined. Survival differences were assessed by log-rank tests and Kaplan-Meier curves. RESULTS: The study identified 972 T2/T3 gastric cancer patients, including 283 differentiated-type patients, 544 undifferentiated-type patients and 145 mixed type. Mixed-type histology was associated with shorter 5-year OS (DT vs UDT vs MT:57.5% vs 44.9% vs 39.6%, P = 0.002). MT histology can be predictive for prognosis of T2/T3 GC patients (HR for OS: 1.386, 95% CI: 1.028-1.868, P = 0.032), and its malignant potential is not inferior to UDT. In the subgroup analysis, MT can potentially be independent risk factor for non-distal GC patients (P = 0.010). CONCLUSION: This study reported that mixed histology could be regarded as a potential prognostic factor for T2/T3 gastric cancer patients, especially for those with non-distal cancer. MT patients have higher incidence of metastasis and recurrence and had poorer prognosis than those with pure histological type. It is necessary for MT patients to have preoperative pathological examination for accurate histologic classification, so as to make the comprehensive treatment strategies..

Central lymph node metastasis is predictive of survival in advanced gastric cancer patients treated with D2 lymphadenectomy.

BACKGROUND: The number of positive lymph nodes, which was defined as "N stage", is mostly used to predict the survival of D2-resected gastric cancer patients, not the location. A "central lymph node" (CnLN) was defined by Ikoma et al., included common hepatic, celiac and proximal splenic artery LNs. CnLNs located in the extraperigastric area are included in the D2 LN station for gastric cancer. We speculate that CnLNs can be regarded as a predictor of survival. METHODS: Eligible advanced gastric cancer patients who underwent curative resection and D2 lymph node dissection between 2004 and 2012 at our institution were identified. The frequency of CnLN metastases and risk factors affecting DFS were examined. Survival differences were assessed by log-rank tests and Kaplan-Meier curves. RESULTS: The study identified 1178 patients who underwent curative surgery or D2 or more extensive lymphadenectomy. A total of 342 patients had been proven to have CnLN metastasis. Larger tumor size (P < 0.001), more frequent lymphatic vessel invasion (P < 0.001), signet ring cell histology (P = 0.014), and more advanced pathological T stage (P = 0.013) were significantly related to CnLNs metastasis. The patients with CnLN metastasis had a poor prognosis (HR for DFS of 1.366, 95%CI = 1.138-1.640, P = 0.001). For the pN2/3 patients, CnLN metastasis was associated with shorter 5-year DFS (for pN2 patients: 25.9% vs 39.3%, P = 0.017; for pN3 patients: 11.5% vs 23.4%, P = 0.005). CONCLUSION: Gastric cancer patients with CnLN metastasis who underwent D2 resection had a poor prognosis. With the same N stage, the patients with positive CnLNs had shorter survival. CnLNs metastasis could be a supplement to N stage and a predictor of survival in gastric cancer patients. Large sample, multicenter, randomized clinical trials are still needed in the future.

Decision-making process during collective movement initiation in golden snub-nosed monkeys (Rhinopithecus roxellana).

Collective decision-making is important for coordination and synchronization of the activities among group-living animals and the mechanisms guiding such procedure involve a great variety of characteristics of behavior and motivation. This study provides some evidence investigating collective movement initiation in a multi-level social band of the golden snub-nosed monkeys (Rhinopithecus roxellana) located in the Mts. Qinling, China. We collect 1223 datum records relevant to decision initiation from six OMUs. The results indicate that collective movement initiation could be divided into two continual but relatively independent processes: decisions on moving direction and movement implementation. In both processes, adult individuals are more likely to initiate the decision-making, while other adults vote on initiator's preference, with a threshold, a supporting number required for a success. Thus, voting behavior and quorum fulfillment contribute to a successful decision-making. Adult individuals play important role in making decisions for moving direction and implementation. For a successful collective movement initiation, the individuals being more central in grooming network initiate decisions more frequently than the others, and attract voters more easily. Furthermore, following the initiation, at least four positive voters are required for a direction decision and at least three positive voters are needed for the decision on movement implementation, which could be considered as the threshold of quorum numbers required for a successful decision. This study has provided some very interesting information and scientific evidence in understanding social structure and behaviors of the nonhuman primates with a social structure very similar to humans'. Thus, some results can directly be referred to the comprehension of human social structure and behavior.

The complete mitochondrial genome of Norfolk Robin (Petroica multicolor: Petroicidae), an endemic endangered species in Norfolk Island.

Norfolk Robin (Petroica multicolor) is mainly distributed in the islands of the southwest Pacific Ocean. It is an endangered species with a declining population and needs urgent protection. Here, we report the first complete mitochondrial genome of Norfolk Robin in the Petroicidae family. The mitochondrial genome is a typically circular genome with a total length of 16,861 bp, and it contains 13 protein-coding genes, 22 tRNA, and 2 rRNA genes. The GC content is 46.3%, and the percent of A, C, G, and T is 29.9%, 31.8%, 14.5%, and 23.7%, respectively. Phylogenetic analysis based on mitochondrial genomes fully supported that the white-eared catbird is closely related to P. goodenovii. The complete mitochondrial genome obtained from the current study can provide more genomic resources and guidance for the conservation biology, taxonomy and population genetics of Norfolk Robin.