Advancing carbohydrate quantification in MALDI mass spectrometry by the rapidly freeze-drying droplet (RFDD) method.

Quantitative carbohydrate analysis faces challenges in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), including insufficient sensitivity and inconsistent spatial distribution of ion intensity. This study introduces an innovative sample preparation approach, the Rapidly Freeze-Drying Droplet (RFDD) method, aimed at overcoming these challenges by enhancing the homogeneity of the sample morphology and signal intensity in MALDI. Compared to conventional preparation methods, the RFDD method reduces the laser energy threshold and demonstrates a remarkable increase in signal intensity for carbohydrates, facilitating the detection of high-molecular-weight polysaccharides (>10 kDa). The RFDD-prepared samples exhibit a uniformly distributed signal intensity that overcomes the 'sweet spot' issue in MALDI. The enhanced signal intensity and reproducibility lead to reliable quantitative analysis of carbohydrates, eliminating the need for expensive isotopic standards in each sample. A straightforward and accessible approach is presented for general laboratories, revolutionizing carbohydrate analysis in MALDI-MS.

Early adenocarcinoma mixed with a neuroendocrine carcinoma component arising in the gastroesophageal junction: A case report.

BACKGROUND: Early adenocarcinoma mixed with a neuroendocrine carcinoma (NEC) component arising in the gastroesophageal junctional (GEJ) region is rare and even rarer in young patients. Here, we report such a case in a 29-year-old Chinese man. CASE SUMMARY: This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation. Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line, without Barrett's esophagus or involvement of the gastric cardia. The nodule was completely resected by endoscopic submucosal dissection (ESD). Pathological examination confirmed diagnosis of intramucosal adenocarcinoma mixed with an NEC component, measuring 1.5 cm. Immunohistochemically, both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%; NEC was positive for synaptophysin and chromogranin. Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene, a common gastric cancer driver gene, in addition to pathogenic somatic mutations in P53 and CHEK2 genes. The patient was alive without evidence of the disease 36 mo after ESD. CONCLUSION: Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.

Abnormal Serum BDNF and p-mTOR in MDD in Adolescents with Childhood Trauma.

Background: Adolescents with major depressive (MDD) episodes associated with childhood trauma have a poorer response to treatment and a higher risk of suicide. The underlying etiology is unclear. Brain-derived neurotrophic factor (BDNF) could improve depressive symptoms by down-regulating mammalian target of rapamycin (mTOR) signaling pathways, which was involved in adverse environmental stimuli during neurodevelopment. BDNF and mTOR have not been reported simultaneously in adolescents with major depressive episodes associated with childhood trauma. Methods: Childhood Trauma Questionnaire-Short Form (CTQ-SF), Children's Depression Inventory (CDI) and Children's Depression Rating Scale-Revised (CDRS-R) were used to evaluate the recruited adolescents with major depression episodes. Serum BDNF and p-mTOR levels were measured by ELISA in 31 adolescents with major depression episodes with childhood trauma and 18 matched healthy control. Results: The serum levels of BDNF were significantly lower (p<0.001); and the serum levels of p-mTOR were high (p=0.003) in the adolescents with the first episode of major depressive episode accompanied by childhood trauma. Of the 31 adolescents with major depressive episodes, 17 had suicide or self-injury. Compared with the healthy control group, the serum levels of BDNF in patients with suicide or self-injury were lower than those without suicide or self-injury(p<0.001); the serum levels of p-mTOR were higher than those without suicide or self-injury (p=0.01). While in patients without suicide or self-injury, only serum p-mTOR was significantly higher than that in healthy group (p=0.028). BDNF was negatively correlated with CDRS-R (r=-0.427, p=0.006), p-mTOR was positively correlated with CDI (r=0.364, p=0.048). According to Receiver Operating Characteristic Curve (ROC), the combination of serum BDNF and p-mTOR levels have better diagnostic value. Conclusion: Neurotrophic and signaling pathways, involving BDNF and p-mTOR, may play a role in adolescent MDD with a history of childhood trauma, especially patients with suicide and self-injury tendencies.

Clinicopathological significance of intestinal metaplasia in endoscopically resected early gastric carcinoma.

OBJECTIVE: To investigate the clinicopathological and prognostic significance of intestinal metaplasia (IM) in endoscopically resected early gastric carcinoma (EGC). METHODS: Altogether 136 consecutive cases with EGC resected by endoscopic submucosal dissection over 5 years were included and divided into the early gastric cardiac (EGCC; n = 60) and non-cardiac carcinoma (EGNCC; n = 76) groups. Goblet cell IM and subtypes were determined with histology and immunostaining. Recurrence-free survival (RFS) was compared among various IM groups. RESULTS: IM was identified in 128 (94.1%) EGC cases, including complete IM (n = 39), incomplete IM (n = 27), and mixed IM (n = 62). Incomplete IM was significantly more common in EGCC and exhibited a lower frequency of en bloc resection than the complete subtype. The frequency of synchronous or metachronous gastric tumor was significantly more common in EGCC with complete IM than in those with incomplete IM. Compared to EGC without IM, EGC with IM showed a significantly higher frequency of non-poorly cohesive carcinoma, en bloc resection, and non-eCuraC-1 grade. EGNCC with IM was significantly associated with negative resection margins and en bloc resection. The 5-year RFS was significantly lower in EGNCC patients with incomplete IM compared with those with mixed IM. The independent risk factors for RFS included tumor size >2 cm and eCuraC-1 grade. CONCLUSIONS: Subtyping IM in EGC helped predict endoscopic resectability, prognosis, and risk of synchronous or metachronous gastric tumor. The significance of IM differed between EGCC and EGNCC. Large studies with longer follow-up are warranted to validate our findings.