Favorable response to PD-1 inhibitor plus chemotherapy as first-line treatment for metastatic gastric mixed neuroendocrine-non-neuroendocrine tumor: a case report.

Gastric mixed neuroendocrine-non-neuroendocrine tumor (MiNEN), a rare malignancy, currently has no standard treatment. Here, we report a patient with pathologically confirmed gastric MiNEN following radical surgery with rapid postoperative distant tumor recurrence. Immunofluorescence results suggested intensive lymphocyte infiltration in the tumor. The programmed death receptor ligand 1 (PD-L1) immunohistochemistry 22C3 pharmDx assay showed tumor proportion score was 5% and combined positive score was 10. After 6 cycles of treatment with etoposide and cisplatin in combination with toripalimab, efficacy was assessed as a complete response. Our report shows that for gastric MiNEN patients with high expression of PD-L1, chemotherapy combined with immune checkpoint inhibitors may achieve more significant efficacy.

The crosstalk between ferroptosis and anti-tumor immunity in the tumor microenvironment: molecular mechanisms and therapeutic controversy.

The advent of immunotherapy has significantly reshaped the landscape of cancer treatment, greatly enhancing therapeutic outcomes for multiple types of cancer. However, only a small subset of individuals respond to it, underscoring the urgent need for new methods to improve its response rate. Ferroptosis, a recently discovered form of programmed cell death, has emerged as a promising approach for anti-tumor therapy, with targeting ferroptosis to kill tumors seen as a potentially effective strategy. Numerous studies suggest that inducing ferroptosis can synergistically enhance the effects of immunotherapy, paving the way for a promising combined treatment method in the future. Nevertheless, recent research has raised concerns about the potential negative impacts on anti-tumor immunity as a consequence of inducing ferroptosis, leading to conflicting views within the scientific community about the interplay between ferroptosis and anti-tumor immunity, thereby underscoring the necessity of a comprehensive review of the existing literature on this relationship. Previous reviews on ferroptosis have touched on related content, many focusing primarily on the promoting role of ferroptosis on anti-tumor immunity while overlooking recent evidence on the inhibitory effects of ferroptosis on immunity. Others have concentrated solely on discussing related content either from the perspective of cancer cells and ferroptosis or from immune cells and ferroptosis. Given that both cancer cells and immune cells exist in the tumor microenvironment, a one-sided discussion cannot comprehensively summarize this topic. Therefore, from the perspectives of both tumor cells and tumor-infiltrating immune cells, we systematically summarize the current conflicting views on the interplay between ferroptosis and anti-tumor immunity, intending to provide potential explanations and identify the work needed to establish a translational basis for combined ferroptosis-targeted therapy and immunotherapy in treating tumors.

Pathogenesis and research progress in leukoaraiosis.

Leukoaraiosis is a common imaging marker of cerebral small vessel disease. In recent years, with the continuous advances in brain imaging technology, the detection rate of leukoaraiosis is higher and its clinical subtypes are gradually gaining attention. Although leukoaraiosis has long been considered an incidental finding with no therapeutic necessity, there is now growing evidence linking it to, among other things, cognitive impairment and a high risk of death after stroke. Due to different research methods, some of the findings are inconsistent and even contradictory. Therefore, a comprehensive and in-depth study of risk factors for leukoaraiosis is of great clinical significance. In this review, we summarize the literature on leukoaraiosis in recent years with the aim of elucidating the disease in terms of various aspects (including pathogenesis, imaging features, and clinical features, etc.).

Effects of magnesium valproate adjuvant therapy on patients with dementia: A systematic review and meta-analysis.

BACKGROUND: Current research has found contradictory results on the treatment of magnesium valproate (VPM) in patients with dementia (PwD). OBJECTIVES: Here, we conducted a meta-analysis to evaluate the efficacy and safety of VPM in the adjuvant treatment of PwD. PURPOSE: Current research has found contradictory results on the treatment of VPM in PwD. Here, we conducted a meta-analysis to evaluate the efficacy and safety of VPM in the adjuvant treatment of PwD. METHODS: MEDLINE via PubMed, Cochrane Library, EBSCO, Embase, China National Knowledge (CNKI), and Wan Fang databases were researched to gather relevant data on magnesium valproate assistant therapy for patients with dementia (PwD) by using medical subject headings and term words. RESULTS: After the final screening, 22 RCT studies (a total of 1899 participants) were included in this meta-analysis, which compared VPM adjuvant treatment with antidementia or psychotropic drug monotherapy. Significant differences were found in the scores on mini-mental state examination (P = .028), Alzheimer disease assessment scale cognitive subscale (P < .05), Bech-Rafaelsen Mania Rating Scale (P < .05), behavioral pathology in Alzheimer disease rating scale (P = .001), activities of daily living (P < .05), and Pittsburgh Sleep Quality Index (P < .05). Besides, the levels of inflammatory factors including IL-1ß, IL-6, and TNF-α were significantly lower than those in the monotherapy group (P < .05). While there was no increase in the incidence of adverse events (P = .383), VPM as an assistant therapy is generally well tolerated in PwD. CONCLUSION: By meta-analysis, evidence was found to support VPM additional used for the treatment of cognitive function, psychiatric symptoms, or disease improvement in PwD. VPM may be a potential drug to aid in the treatment of dementia patients. However, there was lack of enough evidence to classification of dementia severity in our inclusion study. More research is still needed, including clinical trials evaluating VPM as a complementary therapy.

Differential diagnosis and treatment of salivary secretory carcinoma and acinic cell carcinoma.

Secretory carcinoma (SC) and acinic cell carcinoma (AciCC) are two rare tumors originating in the salivary gland of the head and neck. Before the World Health Organization (WHO) classified SC as a new entity in 2017, the majority of SC cases were incorrectly diagnosed as AciCC. Indeed, they are similar in biological behaviors, clinical manifestations and histomorphological features. Especially, SC and zymogen granule-poor AciCC are difficult to differentiate, which brings a tough challenge in clinical diagnosis. This article provides an updated understanding of the differential diagnosis in SC and AciCC from two main perspectives: histopathology and molecular genetics. The targeted therapies for both tumors are also mentioned. It aims to give some hints in clinical diagnosis and treatment, in hopes that patients with adequate diagnosis could obtain the opportunityformore effective treatment.

Depression in patients with epilepsy during the COVID-19 pandemic based on longitudinal self-reporting.

The current study screened major depression in people with epilepsy (PWE) during the epidemic of the novel coronavirus-related disease COVID-19, in order to identify whether the outbreak generated negative psychological impact on PWE. A Chinese version of the Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E), a self-reporting depression inventory, was applied for rapid detection of major depression. Assessment was carried out online during three different periods (prior to, during, and after the outbreak of COVID-19), with the aim of identifying changes in prevalence of depression and associated risk factors. A total of 158 PWE were recruited into the study (48.7% female). The questionnaire completion rates were 94.3% and 70.9% during and after the outbreak, respectively. The prevalence of depression prior to the epidemic, as the baseline, was 34.8% and increased to 42.3% during the period of the epidemic. Towards the end of the outbreak, the prevalence declined towards the baseline (36.6%). Factors such as living alone (OR = 4.022, 95% CI: 1.158-13.971, P = 0.028) and active seizures before the epidemic (OR = 2.993, 95% CI: 1.197-7.486, P = 0.019) were associated with depression during the epidemic. Monotherapy appeared to be protective against depression (OR = 0. 105, 95% CI: 0.047-0.235, P <0.001). Our results suggest that the pandemic exerts negative influence on PWE's mental health. Depression is one of the common psychological disorders that needs greater attention during this extraordinary period.

Epilepsy management during epidemic: A preliminary observation from western China.

OBJECTIVE: This study aimed to investigate whether the proposed model could manage patients with epilepsy (PWEs) during the coronavirus disease 2019 (COVID-19) outbreak. METHODS: We used a model to manage the PWEs during the outbreak. Questionnaire survey and hospital data were used to explore whether PWEs under our management were affected by the virus. RESULTS: A total of 118 (78.7%) PWEs completed the survey. During the "model period," 22.9% (27/118) of the respondents reported antiepileptic drug (AEDs) discontinuity, including six (22.2%) PWEs who failed to purchase AEDs. Of the patients, 40.7% (22/54) failed to attend ordinary clinic, which was higher than that during the "period before model" (7.9%, 5/63). The common causes were movement limits (77.3%) and appointment failure (54.5%). A shift from ordinary clinic toward remote consultation was observed. Of the PWEs, 15.7% (13/83) referred to online pharmacy. 87.5% (14/16) of emergencies related to epilepsy were timely treated. 48.3%of PWEs thought that the epidemic had an impact on accessing medical services. Hospital data indicated that a decline in ordinary clinic visit, inpatient, surgery, and emergency attendance was observed in January and February 2020 and an increase in March 2020, as the epidemic mitigated. By contrast, online clinic visit soared in February, when the outbreak hit hard. In addition, we found no cross-infection of COVID-19 in our hospital and respondents. CONCLUSION: We demonstrated a much-needed model to manage the PWEs during the outbreak. We believed that the core architecture of this model was suitable for the management of other chronic diseases.

Alter between gut bacteria and blood metabolites and the anti-tumor effects of Faecalibacterium prausnitzii in breast cancer.

BACKGROUND: The aim was to evaluate the changes of 16S rDNA sequencing and LC-MS metabolomics in breast cancer and explore the growth inhibition of breast cancer cells by Faecalibacterium prausnitzii. RESULTS: Total 49 significantly different flora and 26 different metabolites were screened between two groups, and the correlation was calculated. Relative abudance of Firmicutes and Bacteroidetes were decreased, while relative abundance of verrucomicrobla, proteobacteria and actinobacteria was increased in breast cancer group. Differentially expressed metabolites were mainly enriched in pathways such as linoleic acid metabolism, retrograde endocannabinoid signaling, biosynthesis of unsaturated fatty acids, choline metabolism in cancer and arachidonic acid metabolism. Lipid upregulation was found in breast cancer patients, especially phosphorocholine. The abundance of Faecalibacterium was reduced in breast cancer patients, which was negatively correlated with various phosphorylcholines. Moreover, Faecalibacterium prausnitzii, the most well-known species in Faecalibacterium genus, could inhibit the secretion of interleukin-6 (IL-6) and the phosphorylation of Janus kinases 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) in breast cancer cells. Faecalibacterium prausnitzii also suppressed the proliferation and invasion and promoted the apoptosis of breast cancer cells, while these effects disappeared after adding recombinant human IL-6. CONCLUSIONS: Flora-metabolites combined with the flora-bacteria (such as Faecalibacterium combined with phosphorocholine) might a new detection method for breast cancer. Faecalibacterium may be helpful for prevention of breast cancer. Faecalibacterium prausnitzii suppresses the growth of breast cancer cells through inhibition of IL-6/STAT3 pathway.