Purpose: Plasmablastic lymphoma (PBL) is a rare, aggressive lymphoma that is characterized by terminal B-cell differ‑ entiation. In the West, PBL usually occurs in patients with immunodeficiencies, particularly those induced by human immunodeficiency virus (HIV) infection. We investigated the clinicopathological features of PBL at a single institute in Taiwan, where HIV infection is rare. Methods: This retrospective chart review identified PBL cases that were treated at a single institute in southern Tai‑ wan between 2008 and 2024. Results: We identified nine patients (four males and five females; median age 71 years). Of the eight patients tested for HIV, only one tested positive. Pathologically, the tumors showed plasmablastic morphology and immunopheno‑ type, and three (33%) cases tested positive for Epstein–Barr virus. Six (67%) patients presented with Stage IV disease, including five (56%) with malignant effusion. Six patients were treated with chemotherapy and the remaining three received only supportive care. During a median follow-up of 10 months, five patients died of progressive disease, two died of unrelated diseases, and two were alive with PBL relapse. Conclusion In Taiwan, PBL constitutes a rare and aggressive clinical condition and is frequently associated with malignant effusion. In contrast to Western patients, the PBL in most patients from Taiwan was unrelated to HIV infection.

Purpose: Plasmablastic lymphoma (PBL) is a rare, aggressive lymphoma that is characterized by terminal B-cell differ‑ entiation. In the West, PBL usually occurs in patients with immunodeficiencies, particularly those induced by human immunodeficiency virus (HIV) infection. We investigated the clinicopathological features of PBL at a single institute in Taiwan, where HIV infection is rare. Methods: This retrospective chart review identified PBL cases that were treated at a single institute in southern Tai‑ wan between 2008 and 2024. Results: We identified nine patients (four males and five females; median age 71 years). Of the eight patients tested for HIV, only one tested positive. Pathologically, the tumors showed plasmablastic morphology and immunopheno‑ type, and three (33%) cases tested positive for Epstein–Barr virus. Six (67%) patients presented with Stage IV disease, including five (56%) with malignant effusion. Six patients were treated with chemotherapy and the remaining three received only supportive care. During a median follow-up of 10 months, five patients died of progressive disease, two died of unrelated diseases, and two were alive with PBL relapse. Conclusion In Taiwan, PBL constitutes a rare and aggressive clinical condition and is frequently associated with malignant effusion. In contrast to Western patients, the PBL in most patients from Taiwan was unrelated to HIV infection.

Purpose: Plasmablastic lymphoma (PBL) is a rare, aggressive lymphoma that is characterized by terminal B-cell differ‑ entiation. In the West, PBL usually occurs in patients with immunodeficiencies, particularly those induced by human immunodeficiency virus (HIV) infection. We investigated the clinicopathological features of PBL at a single institute in Taiwan, where HIV infection is rare. Methods: This retrospective chart review identified PBL cases that were treated at a single institute in southern Tai‑ wan between 2008 and 2024. Results: We identified nine patients (four males and five females; median age 71 years). Of the eight patients tested for HIV, only one tested positive. Pathologically, the tumors showed plasmablastic morphology and immunopheno‑ type, and three (33%) cases tested positive for Epstein–Barr virus. Six (67%) patients presented with Stage IV disease, including five (56%) with malignant effusion. Six patients were treated with chemotherapy and the remaining three received only supportive care. During a median follow-up of 10 months, five patients died of progressive disease, two died of unrelated diseases, and two were alive with PBL relapse. Conclusion In Taiwan, PBL constitutes a rare and aggressive clinical condition and is frequently associated with malignant effusion. In contrast to Western patients, the PBL in most patients from Taiwan was unrelated to HIV infection.

This study aims to explore whether Naoxintong Capsules improve multiple cerebral infarctions and myocardial injury via promoting angiogenesis, thereby exerting a simultaneous treatment effect on both the brain and heart. Male SD rats were randomly divided into six groups: sham-operated group, model group, high-dose, medium-dose, and low-dose groups of Naoxintong Capsules(440, 220, and 110 mg·kg~(-1)), and nimodipine group(10.8 mg·kg~(-1)). Rat models of multiple cerebral infarctions were established by injecting autologous thrombus, and samples were collected and tested seven days after modeling. Evaluations included multiple cerebral infarction model assessments, neurological function scores, grip strength tests, and rotarod tests, so as to evaluate neuromotor functions. Morphological structures of brain and heart tissue were observed using hematoxylin-eosin(HE) staining, Nissl staining, and Masson staining. Network pharmacology was employed to screen the mechanisms of Naoxintong Capsules in improving multiple cerebral infarctions and myocardial injury. Neuronal and myocardial cell ultrastructures were observed using transmission electron microscopy. Apoptosis rate in brain neuronal cells was detected by TdT-mediated dUTP nick end labeling(TUNEL) staining, and reactive oxygen species(ROS) levels in myocardial cells were measured. Immunofluorescence was used to detect the expression of platelet endothelial cell adhesion molecule-1(CD31), antigen identified by monoclonal antibody Ki67(Ki67), hematopoietic progenitor cell antigen CD34(CD34), and hypoxia inducible factor-1α(HIF-1α) in brain and myocardial tissue. Western blot, and real-time quantitative polymerase chain reaction(RT-qPCR) were used to detect the expression of HIF-1α, vascular endothelial growth factor(VEGF), vascular endothelial growth factor receptor 2(VEGFR2), sarcoma(Src), basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1), and TEK receptor tyrosine kinase(Tie-2). Compared with the model group, the medium-dose group of Naoxintong Capsules showed significantly lower neurological function scores, increased grip strength, and prolonged time on the rotarod. Pathological damage in brain and heart tissue was reduced, with increased and more orderly arranged mitochondria in neurons and cardiomyocytes. Apoptosis in brain neuronal cells was decreased, and ROS levels in cardiomyocytes were reduced. The microvascular density and endothelial cells of new blood vessels in brain and heart tissue increased, with increased overlapping regions of CD31 and Ki67 expression. The relative protein and mRNA expression levels of HIF-1α, VEGF, VEGFR2, Src, Ang-1, Tie-2, and bFGF were elevated in brain tissue and myocardial tissue. Naoxintong Capsules may improve multiple cerebral infarctions and myocardial injury by mediating HIF-1α/VEGF expression to promote angiogenesis.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Cerebral Infarction/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Capsules ; Signal Transduction/drug effects* ; Humans ; Brain/metabolism* ; Myocardium/metabolism* ; Apoptosis/drug effects*

This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

ObjectiveTo observe the clinical effect of Jieyu Qingxin formula granules combined with remote interactive cognitive behavioral therapy for insomnia （CBT-I） on chronic insomnia of liver depression and fire-turning type. MethodThis study was a prospective randomized controlled trial. 120 patients with chronic insomnia of liver depression and fire-turning type in Lu'an traditional Chinese medicine Hospital from January 2022 to June 2023 were selected as objects. They were randomly divided into two groups，with 60 cases in each group. The control group received remote interactive CBT-I. The observation group was treated with Jieyu Qingxin formula granules on the basis of the control group. Intervention treatment lasted for four weeks，and observation lasted for six weeks. Comparison of data of each group：clinical efficacy，changes in traditional Chinese medicine （TCM） syndrome score before and after treatment，changes in insomnia severity index （ISI） score，self-rating depression scale （SDS） and self-rating anxiety scale （SAS） score changes，total sleep time，wake time，sleep latency，sleep efficiency， Actigraphy sleep parameter value changes，serum neuron specific enolase （NSE） ，adenosine，dopamine （DA）， 5-hydroxytryptamine （5-HT） level changes，and adverse reactions. ResultThe total effective rate in the observation group （92.45%，49/53） was higher than that in the control group（76.92%，40/52）， and the difference was statistically significant（χ²=4.711 1，P<0.05）. After treatment，TCM syndrome score，ISI score，SAS score， and SDS score were decreased in all groups. The total sleep time was extended，and wake time and sleep latency were shortened. The sleep efficiency was increased，but the NSE and DA levels were decreased. Adenosine and 5-HT levels were increased in all groups（P<0.05）. After treatment，compared with the control group，the observation group had lower TCM syndrome score，ISI score，SAS score， and SDS score，longer total sleep time，higher sleep efficiency，shorter wake time and sleep latency，lower NSE and DA levels， and higher adenosine and 5-HT level （P<0.05）. There was one case of nausea in the observation group and no adverse reaction in the control group during treatment. There was no significant difference between the two groups. ConclusionBy reducing NSE and DA and increasing the levels of 5-HT and adenosine，the anxiety （SAS score） and depression （SDS score） of patients can be improved， so as to improve their sleep and effectively treat chronic insomnia of liver depression and fire-turning type.

Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous study found that oral administration of nitazoxanide inhibited Western diet (WD)-induced hepatic steatosis in ApoE^-/- mice. However, the specific mechanism remains to be elucidated. In the present study, we performed an untargeted metabolomics approach to reveal the effect of nitazoxanide on the liver metabolic profiles in WD-fed ApoE^-/- mice, and carried out the cellular experiments to elucidate the underlying mechanisms. UPLC-MS-based untargeted metabolomics analysis was used to investigate the effect of nitazoxanide on global metabolite changes in liver tissues. The differential metabolites were screened for enrichment analysis and pathway analysis. Hepatocytes were treated with tizoxanide, the metabolite of nitazoxanide, to investigate the underlying mechanism based on the findings in metabolomics study. The improvement of liver lipid metabolism disorders by nitazoxanide treatment in WD-fed ApoE^-/- mice was mainly through regulating glycerophospholipid metabolism, D-glutamine and glutamate metabolism, glutathione metabolism, and arginine biosynthesis metabolism. Tizoxanide, the active metabolite of nitazoxanide, increased glutathione (GSH) contents and glutamate-cysteine ligase catalytic subunit (Gcl-c) and glutathione reductase (Gsr) mRNA expressions in HepG2 cells. Tizoxanide increased cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) protein levels, inhibited lipid accumulation in hepatocytes induced by free fatty acid (FFA). Tizoxanide increased S-adenosyl-L-homocysteine hydrolase (SAHH) protein levels in HepG2 cells and mouse primary liver cells stimulated with free fatty acid (FFA). Tizoxanide increased N-acetyl glutamate synthase (Nags) and carbamoylphosphate synthetase 1 (Cps1) mRNA expressions in HepG2 cells. In conclusion, nitazoxanide improves WD-induced hepatic steatosis in ApoE^-/- mice and the underlying mechanisms include increasing CBS expression, GSH content, PEMT protein expression, Nags and Cps1 mRNA expression in hepatocytes.

Objective:To observe the correlation between retinal capillary density and retinal thickness in the macula and spherical equivalent (SE) in school-age children.Methods:A cross-sectional study. From May to December 2022, 182 school-age children who visited the ophthalmology department of the First Affiliated Hospital of Zhengzhou University were included. There were 95 males and 87 females. The age ranged from 6 to 12 years, and the spherical equivalent (SE) was +0.50 to -6.00 D. They were divided into three groups based on the SE of the right eyes: 54 eyes in emmetropia group (+0.50≤SE<-0.50 D), 71 eyes in low myopia group (-0.50≤SE<-3.00 D), and 57 eyes in moderate myopia group (-3.00≤SE≤-6.00 D). The macular area of 6 mm×6 mm was scanned using swept-source optical coherence tomography angiography and was divided into three concentric rings centered on the fovea, including the macular central fovea (0-1 mm diameter), inner ring (1-3 mm diameter) and outer ring (3-6 mm diameter). The retinal thickness and blood flow density of superficial vascular plexus (SVP) and deep vascular plexus (DVP) in different zones within 6 mm of the macular area were measured. The relationships between SE and SVP, DVP and retinal thickness in each ring region were investigated by univariate and multivariate linear regression analyses, smooth curve fitting, and threshold effects.Results:There were significant differences in the SVP ( F=6.64, 26.06, 22.69) and DVP ( F=7.97, 25.01, 5.09) of macular central fovea, inner ring and outer ring among the emmetropia, low myopia and moderate myopia groups ( P<0.05). Univariate linear regression analysis showed that the SVP ( β=-0.56,-1.17, -0.79) and DVP ( β=-1.03, -0.93, -0.45) of the three regions were positively correlated with SE ( P<0.05). After smooth curve fitting, threshold effect analysis and multivariate linear regression analysis, the SVP and DVP in the macular central fovea were linearly positively correlated with SE ( β=-0.91, -1.40; P<0.05), and SVP and DVP in the inner ring and outer ring showed an inverted U-shaped curve relationship with SE with the inflection (<3.00 D). When the SE was less than <3.00 D, the SVP and DVP in the inner ring and outer ring were positively correlated with SE ( P<0.05). When the SE was higher than -3.00 D, except for the DVP in the inner ring region, the other parameters were negatively correlated with SE ( P<0.05). There were significant differences in retinal thickness of the inner ring and outer ring ( F=5.47, 16.36; P<0.05), and no significant difference in the macular central fovea among the emmetropia, low and moderate myopia groups ( F=2.16, P>0.05). By using univariate and multivariate linear regression analyses, the retinal thickness in the inner ring and outer ring were negatively correlated with SE ( β =1.99, 3.05; P<0.05). However, no correlation was found between retinal thickness and SE in the macular central fovea ( β=-1.65, P>0.05). Conclusions:In school-age children with SE between +0.50 D and -6.00 D, the retinal capillaries density of the macular central fovea gradually increase, and increase first and then decrease in the inner ring and outer ring with increasing SE. The retinal thickness of inner ring and outer ring gradually decrease and not change significantly in the macular central fovea.

ERK1/2 is a key protein that mediates cell signal transduction,and it is involved in regulating biological processes such as chromatin remodeling,nuclear disintegration,proliferation,survival,metabolism,and cell migration and differentiation.Its overactivation is closely related to the occurrence and progression of cancer,and the mechanism is manifested as the overactivation of ERK1/2 by gene mutations of upstream pathway molecules or regulators and the reactivation of ERK1/2 after inhibition against the above targets.ERK1/2 is a potentially valuable target.In this review,the mechanism of post-translational modification and spatial regulation of ERK1/2 and the application status of corresponding small-molecule inhibitors were discussed.The current antitumor strategy of targeting and regulating ERK1/2 was summarized,and the possibility of exploring potential targets was elucidated,thus providing new insights into the developmental research of ERK1/2 as an ideal anticancer target.

Objective To investigate the imaging manifestations and pathogenesis of liver focal nodular hyperplasia-like(FNH-like)lesions in patients undergoing antineoplastic chemotherapy.Methods The clinical and imaging data of focal nodular hyperplasia(FNH)and FNH-like lesions patients confirmed by pathology after antineoplastic chemotherapy were analyzed retrospectively.Results A total of 67 FNH-like nodules were detected in 15 patients after antineoplastic chemotherapy,including multiple FNH nodules in 8 cases and sin-gle nodule in 7 cases.The mean detected time of FNH-like nodules was(18.9±11.7)months.Central scarring could be observed during follow-up in 5 nodules,and the rest showed atypical FNH features.Among 45 nodules examined with hepatocyte-specific con-trast medium,36 nodules showed slightly high signal in the hepatobiliary phase and other 9 nodules showed isosignal.Conclusion FNH-like lesions in patients during antineoplastic chemotherapy have certain imaging features,such as lack of central scarring,gener-ally smaller nodules,delayed enhancement,and hyperenhancement in hepatobiliary-specific phase,which are of significant value in the diagnosis and differential diagnosis of the disease.