Incidence and clinical characteristics of hypertriglyceridemic acute pancreatitis: A retrospective single-center study.

BACKGROUND: The incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) has increased yearly, but updated population-based estimates on the incidence of HTG-AP are lacking. Reducing serum triglyceride (TG) levels quickly is crucial in the early treatment of HTG-AP. Decreased serum TG levels are treated by non-invasive methods, which include anti-lipidemic agents, heparin, low-molecular weight heparin, and insulin, and invasive methods, such as blood purification including hemoperfusion (HP), plasmapheresis, and continuous renal replacement therapy. However, authoritative guidelines have not been established. Early selection of appropriate treatment is important and beneficial in controlling the development of HTG-AP. AIM: To evaluate the effect between patients treated with intravenous insulin (INS) and HP to guide clinical treatment. METHODS: We retrospectively reviewed 371 patients with HTG-AP enrolled in the Department of Fujian Provincial Hospital form April 2012 to March 2021. The inpatient medical and radiologic records were reviewed to determine clinical features, severity, complications, mortality, recurrence rate, and treatment. Multivariate logistic regression analyses were used to analyze risk factors for severe HTG-AP. Propensity score matching was used to compare the clinical outcomes of INS and HP. RESULTS: A total of 371 patients met the HTG-AP criteria. The incidence of HTG-AP was increased by approximately 2.6 times during the 10 years (8.4% in April 2012-March 2013 and 22.3% in April 2020-March 2021). The highest incidence rate of acute pancreatitis was observed for men in the age group of 30-39 years. The amylase level was elevated in 80.1% of patients but was only three times the normal value in 46.9% of patients. The frequency of severe acute pancreatitis (26.9%), organ failure (31.5%), rate of recurrence (32.9%), and mortality (3.0%) of HTG-AP was high. Improved Marshall score, modified computed tomography severity index score, baseline TG, baseline amylase, C-reactive protein (CRP), albumin, aspartate aminotransferase, low-density lipoprotein cholesterol, urea nitrogen, creatinine, calcium, hemoglobin, free triiodothyronine, admission to intensive care unit, and mortality were significantly different between patients with different grades of severity (P < 0.050). Multivariate logistic regression analysis confirmed that high CRP [P = 0.005, odds ratio (OR) = 1.011, 95%CI: 1.003-1.019], low calcium (P = 0.003, OR = 0.016, 95%CI: 0.001-0.239), and low albumin (P = 0.023, OR = 0.821, 95%CI: 0.693-0.973) were risk factors of severe HTG-AP. After propensity score matching adjusted by sex, age, severity of HTG-AP, and baseline TG, the serum TG significantly decreased in patients treated with INS (P < 0.000) and HP (P < 0.000) within 48 h. However, the clearance rate of TG (57.24 ± 33.70% vs 56.38 ± 33.61%, P = 0.927) and length of stay (13.04 ± 7.92 d vs 12.35 ± 6.40 d, P = 0.730) did not differ between the two groups. CONCLUSION: The incidence of HTG-AP exhibited a significant increase, remarkable severity, and recurrent trend. Patients with mild and moderately severe acute pancreatitis can be treated effectively with INS safely and effectively without HP.

Identification of differentially expressed miRNAs derived from serum exosomes associated with gastric cancer by microarray analysis.

AIMS: To explore the differentially expressed microRNAs (DEMs) in serum exosomes between gastric cancer (GC) patients and healthy people to provide new targets for GC diagnosis and treatment. METHODS: DEMs in serum exosomes were screened by microarray analysis and verified by RT-qPCR. The target genes of DEMs were predicted using Targetscan and miRTarBase databases and then overlapped with the DEGs of STAD in TCGA database to obtain the common target genes. Biological function and pathway enrichment were analyzed using enrichr database, and a PPI network was constructed using STRING database. The potential target genes of DEMs were identified using the MCODE and cytoHubba plug-ins of Cytoscape software. Survival analysis were conducted using KMP and TCGA databases. The DEMs -target genes-pathways network was established using Cytoscape software. A Cox proportional hazards regression model formed by optimal target genes was used to access the reliability of this prediction process. RESULTS: Three serum exosomal microRNAs (exo-miRNAs, has-miR-1273 g-3p, has-miR-4793-3p, has-miR-619-5p) were identified to be highly expressed in GC patients and performed excellent diagnostic ability. A total of 179 common target genes related to GC were predicted. They were mainly involved in 79 GO functional annotations and 6 KEGG pathways. The prognostic model formed by eight optimal target genes (TIMELESS, DNA2, MELK, CHAF1B, DBF4, PAICS, CHEK1 and NCAPG2), which were low-risk genes of GC, also performed perfect prognostic ability. CONCLUSIONS: Serum exosomal has-miR-1273 g-3p, has-miR-4793-3p and has-miR-619-5p can be used as new diagnostic biomarkers for GC. Among them, serum exosomal hsa-miR-1273 g-3p / hsa-miR-4793-3p targets MELK and hsa-miR-619-5p targets NCAPG2 were identified as novel mechanisms involved in the development of GC. It provides new targets for the diagnosis and treatment of GC by exo-miRNAs.

Analysis of the efficacy of a modified posteromedial approach for Klammer III posterior Pilon fractures.

PURPOSE: To analyze the curative effect and technical points of a modified posteromedial approach in the treatment of Klammer III posterior Pilon fracture. METHODS: A retrospective analysis of patients with Klammer III posterior Pilon fractures were conducted in our department from January 2018 to December 2019. Before the surgery, the patients were fully relieved of swelling and pain, and a comprehensive examination was carried out. The posteromedial approach exposed the posterior and medial fracture block of the distal tibia. According to the fracture of external malleolus, it is determined whether to combine a lateral incision and protect tendons and vascular nerves by a retractor, and then perform a fracture reduction and internal fixation. Postoperatively, the patients were treated with analgesia, detumescence, anticoagulation and rehabilitation exercise. The American orthopaedic foot and ankle society (AOFAS) score and visual analogue score were recorded at regular follow-up after surgery. A t-test was used for the comparison of the preoperative and final AOFAS score. RESULTS: There were 7 male and 13 female (n = 20) included in the study, aged 22 to 88 years (average age 54.2 years). The injury mechanisms were falling from a height (n = 7), traffic accident (n = 6), walking injury (n = 2) and heavy injury (n = 5). The postoperative follow-up duration was 12-24 months (mean 16.95 months). The AOFAS score of the 20 patients before and after surgery were compared. The preoperative AOFAS score was 38.90 ± 3.91, and the final AOFAS score was 80.55 ± 4.20, (p < 0.001). The mean final visual analogue scores at rest, active and weight-bearing walking were 0.30, 0.85 and 1.70, respectively. One patient reported poor postoperative wound healing and required a return to hospital for debridement and anti-infection treatment. CONCLUSION: In the treatment of Klammer III posterior Pilon fractures, the modified posteromedial approach can fully expose the fracture block and the collapsed articular surface of the medial malleolus, achieve good reduction and internal fixation with limited injury of the tendon and vascular nerves, and have a better prognosis.

Construction of PD1/CD28 chimeric-switch receptor enhances anti-tumor ability of c-Met CAR-T in gastric cancer.

Chimeric antigen receptor (CAR) T cell is a promising method in cancer immunotherapy but faces many challenges in solid tumors. One of the major problems was immunosuppression caused by PD-1. In our study, the expression of c-Met in GC was analyzed from TCGA datasets, GC tissues, and cell lines. The c-Met CAR was a second-generation CAR with 4-1BB, cMet-PD1/CD28 CAR was c-Met CAR adding PD1/CD28 chimeric-switch receptor (CSR). In vitro, we measured the changes of different subgroups, phenotypes and PD-1 expression in CAR-T cells. We detected the secretion levels of different cytokines and the killing ability of CAR-Ts. In vivo, we established a xenograft GC model and observed the anti-tumor effect and off-target toxicity of different CAR-Ts. We find that the expression of c-Met was increased in GC. CD3+CD8+ T cells and CD62L+CCR7+ central memory T cells (TCM) were increased in two CAR-Ts. The stimulation of target cells could promote the expression of PD-1 in c-Met CAR-T. Compared with Mock T, the secretion of cytokines as IFN-γ, TNF-α, IL-6, IL-10 secreted by two CAR-Ts was increased, and the killing ability to c-Met positive GC cells was enhanced. The PD1/CD28 CSR could further enhance the killing ability, especially the long-term anti-tumor effect of c-Met CAR-T, and reduce the release level of IL-6. CAR-Ts target c-Met had no obvious off-target toxicity to normal organs. Thus, the PD1/CD28 CSR could further enhance the anti-tumor ability of c-Met CAR-T, and provides a promising design strategy to improve the efficacy of CAR-T in GC.