Advances in Clinical and Experimental Medicine最新文献

Several novel drugs for multiple myeloma, including monoclonal and bispecific antibodies, immunomodulatory agents, and newer-generation proteasome inhibitors, have been introduced over the last decade. Based on the results of randomized clinical trials, the drugs have been incorporated into current treatment recommendations, with the most substantial changes observed in patients under the age of 75. However, new therapeutic options have been indirectly proposed for patients over 75, despite the lack of conclusive data from randomized prospective trials. This paper outlines the development of myeloma therapy and summarizes the current treatment recommendations for patients over 75 by systematically reviewing the most crucial studies involving this group of individuals, with a focus on evaluating treatment safety and efficacy. Melphalan-prednisone (MP), bortezomib plus MP (VMP), lenalidomide-dexamethasone (Rd), and bortezomib plus Rd (VRd) regimens have evolved over the past few years as therapies of choice for the first-line treatment of these patients. A breakthrough came with daratumumab, which increased response rates, extended median progression-free survival (PFS) and overall survival (OS) in the absence of significantly increased toxicity when added to the above regimens.

Background: Age-related macular degeneration (AMD) is considered one of the most common causes of irreversible blindness among elderly patients. Neovascular AMD, which accounts for 10% of all AMD cases, can cause devastating vision loss due to choroidal neovascularization (CNV). The clinical effects and safety of intravitreal injection of conbercept in patients suffering from neovascular AMD have not been fully evaluated.

Objectives: The aim of the study was to evaluate the efficacy and safety of intravitreal injection of conbercept in patients with neovascular AMD with different levels of inflammation.

Material and methods: A total of 120 consecutive patients with neovascular AMD who underwent intravitreal injection of conbercept (3 injections per month + pro re nata (3 + PRN)) were included and stratified based on the intraocular level of high-sensitivity C-reactive protein (hs-CRP). The level of inflammation was defined as low, medium or high, based on the concentration of hs-CRP prior to injection. Before and after conbercept injections, best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were compared, respectively. Moreover, cytokine markers as well as the frequency of injections and adverse events (AEs) were measured.

Results: There were significant differences in BCVA and CRT between low, medium and high tertiles. Compared to the baseline, improved BCVA was observed, and CRT declined significantly after operation. Adverse events were most observed in high tertiles. A significant decrease in vascular endothelial growth factor (VEGF), interleukin (IL)-6 and IL-8 was observed after 1 year.

Conclusions: The effectiveness of conbercept on neovascular AMD varies depending on the level of inflammation, which could be achieved by administering different injection frequencies at different levels of inflammation. Furthermore, conbercept is associated with the reduction of inflammatory factor (IL-6 and IL-8) levels after intravitreal injection, which suggests that suppressing inflammatory response might contribute to the clinical efficacy of anti-VEGF treatment. Our results provide a novel mechanism for conbercept in patients with neovascular AMD.

Background: Previous research has shown that moral judgments are affected by social cognitive abilities, such as theory of mind (ToM). This study examines how information about an actor's beliefs and the consequences of their actions affect the moral evaluation of the character's behavior in social events. Our research builds upon previous studies, which have shown that these factors contribute differently to moral judgments made by both adults and young children.

Objectives: This study aimed to explore how participants with schizophrenia and healthy controls read stories about social situations in the context of moral judgments.

Material and methods: The study used the research procedure that included 4 variants of 16 scenarios describing social situations, and thus comprising 64 stories. After each story, participants evaluated their confidence level on a 4-point scale. To assess delusional beliefs, the Polish adaptation of the Peters Delusion Inventory (PDI) questionnaire and the Paranoia Checklist (PCh) were used. Respondents completed these questionnaires after completing the scenario test procedure.

Results: In social situations, patients with paranoid schizophrenia were found to evaluate actions of protagonists who attempted to harm another person more leniently than when it was an accident. Conversely, healthy individuals judged those actors who expressed intentions to hurt another person significantly more harshly than in an accident situation. Metacognition measures show that paranoid schizophrenia patients make moral judgments with high confidence, despite being based on an incorrect reading of the other person's intentions.

Conclusions: The study indicates that ToM has a significant impact on the moral judgment of others. Decreased moral cognition can result from both positive and negative symptoms. Deficits related to metacognition can also sustain such cognitive distortions.

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic condition with relapsing-remitting course. Diarrhea and abdominal pain are the most common IBD symptoms. Fibroblast growth factor 19 (FGF19) is an endocrine factor that inhibits hepatic bile acid production and may be used as a diagnostic marker for bile acid malabsorption.

Objectives: To assess serum FGF19 levels in active and inactive phases of IBD and find a potential correlation between FGF19 and disease activity.

Material and methods: Fasting serum FGF19 levels were measured in 105 IBD patients (47 UC patients, 41 CD patients without previous ileocecal resection (NR-CD), 17 CD patients after ileocecal resection (IR-CD), and 17 control subjects). The disease activity was assessed using clinical, laboratory and endoscopic criteria.

Results: Inverse correlations were found between FGF19 level and intensity of diarrhea (in UC), abdominal pain intensity (in UC and IR-CD) and inflammatory markers (in UC and IR-CD). Moreover, FGF19 concentration was inversely correlated with clinical and endoscopic activity indices in UC and CD.

Conclusions: Fluctuations in FGF19 level related to clinical and endoscopic activity of UC and CD revealed a clear pattern of higher values in remission than in active disease phases. Fibroblast growth factor 19 may serve as a potential diagnostic biomarker and constitute a new therapeutic target in IBD.

Background: Inflammation is a biological response of the immune system to harmful stimuli. Penehyclidine hydrochloride (PCH) can alleviate inflammation and oxidative stress by activating reactive oxygen species (ROS), nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase 1 (HO-1) in animal models, but there is a lack of cellular evidence.

Objectives: This study investigated the effects of PHC on lipopolysaccharide (LPS)-induced inflammation response and oxidative stress in RAW264.7 cells.

Material and methods: RAW264.7 cells were treated with 1 μg/mL or 5 μg/mL of PHC, with interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), IL-1β, and prostaglandin E2 (PGE2) levels measured with enzyme-linked immunosorbent assay (ELISA) and nitric oxide (NO) measured using the Griess test. Reactive oxygen species were examined with flow cytometry and immunofluorescence, and b-related factor 2 (BRF-2) and NAD(P)H-quinone oxidoreductase 1 (NQO1) using western blot.

Results: Penehyclidine hydrochloride partly, but substantially, reversed LPS-related NO and PGE2 production by RAW264.7 cells in a dose-dependent manner and suppressed LPS-induced expression of IL-6, TNF-α and IL-1β messenger ribonucleic acid (mRNA), secretion of IL-6, TNF-α and IL-1β, and ROS production. Lipopolysaccharide stimulation did not affect Nrf2, heme oxygenase 1 (HO-1) or NQO1 protein expression in RWA264.7 cells not treated with PHC. However, PHC treatment significantly elevated Nrf2, HO-1 and NQO1 protein in LPS-treated RWA264.7 cells, an effect that was dose-dependent. The ROS scavenging using N-acetyl-L-cysteine abolished the PHC-induced upregulation of Nrf2 and HO-1.

Conclusions: Penehyclidine hydrochloride may alleviate LPS-induced inflammation and oxidative stress by activating Nrf2 signaling in RAW264.7 macrophages. These findings suggest that PHC could alleviate inflammation by targeting activated macrophages.

Acute ischemic stroke (AIS) has a high rate of death and causes long-term disability, leading to a global economic burden annually. Therefore, discovering biomarkers to improve AIS patient prognosis is critical. Previous studies reported an association between serum cystatin C (CysC) levels and outcomes in AIS patients, but the results remain controversial. This systematic review and meta-analysis aimed to explore the relationship between serum CysC and AIS patient outcomes using currently available studies. The literature search included PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wan Fang databases. Outcomes included poor functional recovery, cognitive dysfunction and death. Weighted mean difference (WMD) with 95% confidence interval (95% CI) was used as an effect index for measurement data. Results demonstrated that serum CysC was significantly higher in AIS patients with poor functional recovery (WMD = 0.18, 95% CI: 0.08-0.28), cognitive dysfunction (WMD = 0.16, 95% CI: 0.09-0.23) and death (WMD = 0.32, 95% CI: 0.02-0.62) than in the control groups when follow-up time was <1 month. These findings show that high serum CysC levels were associated with poor AIS patient outcomes. Further studies are needed to examine whether reducing serum CysC can prevent poor outcomes in AIS patients.

Background: Emergency medical teams are a crucial component of healthcare systems, routinely providing essential care to pregnant patients in various situations.

Objectives: To evaluate the rate and outcomes of out-of-hospital deliveries attended by Emergency Medical Services (EMS) in Poland and identify areas for improvement in the care provided by emergency medical teams.

Material and methods: This retrospective study was based on 41,335 EMS emergency calls to women in advanced pregnancy, of which 879 births were delivered directly by medical teams between January 2018 and December 2022. Data were obtained from the Polish National Monitoring Center for Emergency Medical Services, encompassing all EMS interventions in Poland.

Results: The study involved 879 EMS team interventions for pregnant women, with an average patient age of 29.87 years. Most patients were in their 2nd pregnancy (28.26%) and delivering for the 2nd time (25.77%). The postnatal condition of newborns, assessed using the Apgar score, was missing in 408 cases (46.52%) due to incorrect completion of documentation. Emergency Medical Services teams, predominantly P-type (basic) teams, handled 69.78% of deliveries, while S-type (specialist) teams were involved in 30.22% of cases. Medical procedures often performed during childbirth included manual assistance in spontaneous delivery, pulse oximetry, physical examination, examination of systemic blood pressure, obtaining peripheral intravenous access, and gynecological examination.

Conclusions: Given the rate of encountered cases and the gaps identified in medical documentation, there is merit in potentially implementing a dedicated form to be completed by medical teams when caring for a pregnant patient. Ongoing training and enhancements in the range of assistance provided to the mother and newborn are imperative for ensuring appropriate care.

Background: Oxidative damage plays an important role in the progression of rheumatoid arthritis (RA). Emerging research evidence suggests that natural antioxidants may effectively ameliorate this disease.

Objectives: To investigate the therapeutic effect of echinacoside (ECH) in a collagen-induced arthritis (CIA) mouse model and thus elucidate the underlying molecular mechanism in RA.

Material and methods: Collagen-induced arthritis mice were intraperitoneally administered 1% dimethyl sulfoxide (DMSO) (control) or 0.6 mg of ECH every other day for 1 month. Arthritis scores and the number of affected paws were assessed. On day 60, mice were euthanized, synovial tissue specimens were obtained, and serum interleukin (IL)-6 and IL-1â expression levels were measured. Mitochondrial morphologies, reactive oxygen species (ROS) content, expression of dynamin-related protein 1 (Drp1), IL-6, nod-like receptor protein 3 (NLRP3), kelch-like ECH-associated protein 1 (Keap1), and nuclear factor-erythroid-2-related factor 2 (Nrf2) contents in synovium were analyzed and compared between DMSOand ECH-treated CIA mice.

Results: Following ECH treatment, mitochondria of CIA-induced mice were found to be elongated, while their arthritis scores, inflammation and the number of affected paws, and the expression levels of Drp1, NLRP3, IL-6, ROS, and Keap1 were all found to be significantly reduced. Conversely, the level of antioxidant factor Nrf2 was found to be elevated. Further, mitochondrial fission was found to be inhibited in synovial tissues.

Conclusions: Our findings validate the therapeutic efficacy of ECH in the CIA mouse model. Echinacoside may suppress oxidative stress and inhibit inflammation by regulating the Nrf2/Drp1 pathway, thus supporting its utility in the treatment of RA.

Background: Recent studies have indicated that the skin lymphatic system and interstitium may play a role in the pathophysiology of arterial hypertension (AH).

Objectives: We aimed to determine whether the set of pathway parameters described previously in rodents would allow for the distinction between hypertensive and normotensive patients.

Material and methods: Molecular and histopathological parameters from the skin and blood of patients with AH (AH group, n = 53), resistant AH (RAH group, n = 32) and control (C group, n = 45) were used, and a statistical multivariate bootstrap methodology combining partial least squares-discriminant analysis (PLS-DA) and selectivity ratio (SR) were applied.

Results: The C vs RAH model presented the best prediction performance (AUC test = 0.90) and had a sensitivity and specificity of 73.68% and 83.33%, respectively. However, the parameters selected for the C vs AH group model were the most important for the pathway described in the rodent model, i.e., greater density of the skin lymphatic vessels (D2-40 expression) and greater number of macrophages (CD68 expression), higher expression of the messenger ribonucleic acid (mRNA) of nuclear factor of activated T cells 5 (NFAT5), vascular endothelial growth factor C (VEGFC) and podoplanin (PDPN) in the skin, greater concentration of hyaluronic acid (HA) in the skin, and lower serum concentration of VEGF-C.

Conclusions: Our study suggests that the NFAT5/VEGF-C/lymphangiogenesis pathway, previously described in rodent studies, may also be present in human HA. Further experiments are needed to confirm our findings.

Background: Chronic obstructive pulmonary disease (COPD) is a complex, heterogeneous disease with multiple extrapulmonary manifestations, among which vitamin D deficiency and insufficiency are very common in COPD and are associated with the health status and clinical outcomes of COPD patients.

Objectives: This paper aims to analyze the impact of leisure-time physical activity (LTPA) and daily sitting time (DST) and their interactions on serum vitamin D in patients with COPD.

Material and methods: Participants aged ≥40 years from the National Health and Nutrition Examination Survey (NHANES) in the USA from 2007 to 2012 who had undergone pulmonary function tests and vitamin D tests were selected as the study participants. Participants' LTPA and DST were assessed using the General Practice Assessment Questionnaire (GPAQ). Multivariate logistic regression analysis was used to analyze the relationship between serum vitamin D, LTPA, DSA and the combination of the 2 in patients with COPD, and the results were expressed as odds ratio (OR) and 95% confidence interval (95% CI).

Results: This study included 1,448 samples. The mean vitamin D concentration of the samples was (68.27 ±26.78) nmol/L; 360 participants (24.86%) had vitamin D deficiency and 539 participants (37.22%) had vitamin D insufficiency. Vitamin D and 25(OH)D3 expression levels differed across the 4 groups (150 min/week and DST > 8 h revealed the highest vitamin D expression levels, while LTPA 8 h showed the lowest. Vitamin D was weakly correlated with FEV1, FVC, BMI, age, and LTPA (p < 0.01), but not with DST. Body mass index (BMI) was weakly positively correlated with DST (r = 0.142, p < 0.01).

Conclusions: Serum physical activity and DST independently affect vitamin D levels in COPD patients; therefore, increasing physical activity and minimizing DST may help improve vitamin D levels and prevent vitamin D deficiency.