Journal of Investigative Medicine最新文献

Accurate knowledge of fibrosis levels is essential for effective treatment decisions and prognostication in chronic hepatitis B (CHB) infection. Current guidelines recommend liver biopsy and elastography as the most reliable methods for assessing fibrosis in CHB patients. However, these methods are not widely implemented due to the limited availability, high costs, and invasiveness of liver biopsy. Thus, we aimed to identify simple clinical predictors of significant liver fibrosis in CHB patients in daily practice. We prospectively recruited CHB patients to undergo shear wave elastography (SWE), abdominal ultrasound, and blood tests. In parallel, we extracted data on patient demographics, habits, medical backgrounds, medications, and CHB status and treatment. Multivariate logistic regression analyses were used to determine predictors of significant fibrosis. Of the 173 patients included in the final analysis, 40 (23.0%) had evidence of significant fibrosis on two-dimensional SWE. Age> 50 years [odds ratio (OR): 3.53; 95% confidence interval (CI): 1.34-9.25; P= 0.001], alanine aminotransferase > 40 (OR: 8.16; 95%CI: 4.6-15.3; P= 0.001), hepatitis B virus DNA> 2000 (OR: 9.20; 95%CI: 3.4-19.0; P< 0.001), concomitant diabetes mellitus (OR: 3.58; 95%CI: 1.89-5.49; P= 0.040), moderate to severe steatosis on ultrasound (OR: 4.50; 95%CI: 2.35-9.95; P= 0.014), and heavy smoking were independent predictors of significant fibrosis. In conclusion, we identified clinical and laboratory variables that may effectively identify CHB patients at high risk of significant fibrosis. These can aid in resource allocation in daily practice with limited resources.

To investigate the differences in relative mRNA expression levels of the novel iron regulatory erythroid factors FAM210B, CCDC115, HO-1, PCBP1, PCBP2, NCOA4, and Nrf2 in children with β-thalassemia major (β-TM) before and after transfusion therapy. A total of 98 children with transfusion-dependent β-thalassemia were recruited from the First Affiliated Hospital of Guangxi Medical University between October 2022 and May 2023. The children were classified based on their hemoglobin (Hb) levels: 57 cases with Hb ≤ 90 g/L and 41 cases with Hb > 90 g/L. Real-time fluorescence quantitative PCR was employed to assess the relative mRNA expression between the groups. The mRNA expression levels of FAM210B, HO-1, and NCOA4 were significantly higher in the Hb ≤ 90 g/L group compared to the Hb > 90 g/L group (P < 0.05). Moreover, higher relative expression levels of FAM210B and NCOA4 correlated with an increased likelihood of requiring blood transfusions in β-TM children. The differences in the remaining factors did not reach statistical significance. FAM210B and NCOA4 may serve as indicators of erythropoiesis and the degree of anemia in children with β-TM. Further research is warranted to explore their potential as therapeutic targets for β-thalassemia and other erythropoietic disorders.

Not needed.

Systemic lupus erythematosus (SLE) is linked with an increased risk of cancers, particularly hematologic malignancies. Cancer mortality among patients with SLE in the United States (U.S.) remains unclear. Our cross-sectional study sought to measure trends in cancer mortality among patients with SLE in the last 2 decades. Cancer deaths among patients with SLE from 1999 to 2020 were analyzed from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). Age-adjusted mortality rates (AAMRs) per 1,000,000 individuals were measured. We used joinpoint trend analysis to determine the average annual percent change (AAPC) in AAMR trends. From 1999 to 2020, there were 2,481 cancer deaths with comorbid SLE. Overall, the AAMRs of cancer among patients with SLE increased from 0.71 in 1999 to 1.19 per 1,000,000 individuals 2020 with the AAPC at +1.19. Women had a higher AAMR from cancer death with comorbid SLE than men (1.39 vs. 0.29 per 1,000,000 individuals). The highest AAMR was observed among African Americans (1.23 per 1,000,000 individuals), followed by Hispanics (0.61 per 1,000,000 individuals), Whites (0.58 per 1,000,000 individuals), and Asians (0.36 per 1,000,000 individuals). Those who lived in the West region and the rural region had the highest AAMR respectively (0.69 vs. 0.70 per 1,000,000 individuals). The three most common causes of cancer deaths were lung cancer (28.70%), breast cancer (8.83%), and non-Hodgkin lymphoma (4.96%). Cancer mortality in SLE patients has risen, with higher rates among African Americans, highlighting the need for targeted interventions.

Methamphetamine use is associated with a range of cardiovascular conditions, including hypertension and heart failure. Beta-blocker use is commonly avoided when treating patients intoxicated with methamphetamines due to a fear of inducing unopposed alpha stimulation and worsening hypertension. We performed a retrospective review of medical records in a county hospital in California with a high prevalence of methamphetamine users. We included adults who tested positive for methamphetamines on urine toxicology, subjects who received beta-blockers within 48 h of their arrival were assigned to the case group, and those who received a non-beta-blocker antihypertensive or no antihypertensive were assigned to the control group. We compared the length of stay (LOS), readmission rate within 30 days, and systolic blood pressure (SBP) and diastolic blood pressure (DBP) between the groups at admission and 24 h. There was no significant difference between LOS and 30-day readmission rates between subjects who received beta-blockers and subjects who did not. Subjects who received carvedilol were compared to subjects in the control group who received another antihypertensive. SBP was significantly higher in the carvedilol group at admission, but there was no significant difference between groups after 24 h, and there was no significant difference in LOS. Treatment with beta-blockers in the case group did not increase LOS or readmission rates compared to the control group, and treatment with carvedilol effectively reduced SBP in patients with hypertension and methamphetamine-induced cardiomyopathy. Our results indicate that beta-blockers, particularly carvedilol, are an effective treatment modality in methamphetamine users.

Metformin, an oral hypoglycemic agent, is commonly used in patients with type II diabetes mellitus. Studies have shown its use is associated with a reduction in major cardiovascular events (MACE) in patients with type 2 diabetes such as hospitalization for acute myocardial infarction, stroke, transient ischemic attack, or cardiovascular death. There is also a suggestion that metformin may have effects beyond those relating to lowering of blood sugar. The goal of this review is to assess the effects of metformin in coronary artery disease (CAD), but more importantly, its effects on disease states other than CAD.

Despite the significant progress of DNA profiling in forensic science, the extraction of DNA from challenging samples remains a formidable obstacle in forensic laboratories. Particularly, hard tissues (bones, teeth, hair, and nails), formalin-fixed tissues, and contaminated samples pose considerable difficulties. DNA extraction from such samples is often complicated, resulting in scanty, degraded, and contaminated DNA. Moreover, the presence of inhibitors from the surrounding environment further hinders DNA quantification and amplification, presenting additional challenges. This review article delves into the molecular basis of these challenges and examines the mechanistic principles underlying standard DNA extraction protocols. To overcome these obstacles, skilled efforts and additional pre-processing techniques are generally required before organic or silica column-based DNA extraction. Such techniques may involve scraping the waste, sample cleaning with detergents, disinfecting, demineralization of bones and teeth, long proteolytic enzyme treatment, in some cases, harsh methods like hot alkali treatment, tailored to the specific sample type. By addressing these challenges and understanding the molecular intricacies involved in DNA extraction, forensic scientists can improve the reliability and success rate of DNA analysis from difficult forensic samples. This review serves as a comprehensive resource for understanding the complexities of DNA extraction and offers potential solutions for recovering the DNA from highly challenging samples.

Background: Peripheral frequency of inducible T cell co-stimulator (ICOS)+CD4 T cells is associated with immunotherapy in gastric cancer (GC); however, limited studies have clarified its association with chemotherapy response.

Methods: This was a prospective, pilot study. A total of 120 participants with newly diagnosed GC and 50 advanced GC patients were recruited; and their prognosis and survival were assessed. The frequency of ICOS+CD4 T cells was examined using flow cytometry.

Results: The frequency of ICOS+CD4 T cells in stage III GC patients was significantly higher than that of other stages patients. In xenograft GC animals, the frequency of ICOS+CD4 in peripheral blood was positively correlated with tumor volume in mice (P=0.0496). High frequency of peripheral ICOS+CD4 was significantly positively correlated with peripheral IFN-γ concentration. Co-culture experiments showed that the presence of GC cells increased the ratio of ICOS+CD4 T cells derived from peripheral blood. The initial peripheral frequency of ICOS+CD4 T cells in the GC progression-group was significantly lower than that in the stable-group after 3 months of platinum-based chemotherapy (P=0.0318).

Conclusion: The frequency of ICOS+CD4 can effectively predicts the short-term progression risk for resectable advanced GC under platinum-based chemotherapy.

Combined administration of two or more drugs is emerging as a new strategy in triple-negative breast neoplasms. This is the first study to investigate the combination of the histone deacetylase inhibitor mocetinostat and the antimetabolite drug capecitabine in triple-negative mammary neoplasms in a preclinical mouse model. Thirty-five female mice were grouped into the control group, capecitabine group, mocetinostat group, and combined drugs group. At the end of the experimental period, body weight, and tumor weight were measured and tumor tissue and lung tissue were histologically examined. The results showed that the body weight of mice in the drug-treated groups was reduced by about 18%. Tumor weights were also reduced by 21% in the mocetinostat group, 27.5% in the capecitabine group, and 45% in the combined group. The combination of mocetinostat and capecitabine decreased the formation of tumors and metastases in lung tissue. In summary, the combination of mocetinostat and capecitabine was more effective than either drug alone in reducing the size of triple-negative breast neoplasms in a mouse model.

Pancreatic cancer is characterized by occult onset, low early diagnosis rate, rapid progress, and poor prognosis. Due to the low response rate and low programmed cell death ligand 1 (PD-L1) expression in pancreatic cancer, the therapeutic application of PL-L1 inhibitors in pancreatic cancer is greatly limited. In vitro studies showed that the expression of PD-L1 increased in pancreatic cancer cells stimulated by fluorouracil (5-FU). We aim to explore the combined effect of 5-FU and anti-PD-L1 antibodies and to provide a reference for the clinical application of PD-L1 antibodies in pancreatic cancer. In the current study, male BALB/c mice were adopted to construct a tumor-bearing model of pancreatic cancer cells. 5-FU and anti-mouse PD-L1 antibodies were combined and administered to evaluate their synergistic effects. The enhancing immune cytotoxicity effect of 5-FU sensitizing the anti-PD-L1 antibody in vivo and in vitro was analyzed by immunohistochemistry and western blot assays. Results showed that 5-FU and anti-PD-L1 antibody combination increased the expression of PD-L1 and IFN-γ, and infiltration of CD8⁺ T lymphocytes in pancreatic xenograft tumor tissues, which was proven by immunohistochemistry and western analysis. Moreover, the combination with the 5-FU remarkably enhanced the immune cytotoxicity of anti-PD-L1 antibodies in mice. In vitro analysis demonstrates that 5-FU increases the expression of PD-L1 on the surface of pancreatic cancer cell lines via up-regulating nuclear factor kappa B (NF-κB) and Protein kinase B (AKT) pathways. This synergistic effect could be abolished by NF-κB and AKT inhibitors.