Stroke is the main cause of death and disability among adults in China and is characterized by high incidence， disability， mortality， and recurrence rates. The combination of traditional Chinese and Western medicine has great potential in treating stroke and its sequelae. The classic traditional Chinese medicine prescription Da Chengqitang （DCQT） has a long history and proven efficacy in treating stroke. Clinically， DCQT is often used to treat stroke and its sequelae. However， the number and quality of clinical trials of DCQT in treating stroke need to be improved. Because of the insufficient basic research， the active ingredients and multi-target mechanism of action of DCQT remain unclear. Our research group has previously confirmed that DCQT can effectively reverse neurological damage， reduce iron deposition， and downregulate the levels of pro-inflammatory cytokines in the rat model of hemorrhagic stroke. The treatment mechanism is related to the nuclear factor erythroid 2-related factor 2 （Nrf2）-mediated signaling pathway and p38 mitogen-activated protein kinase （MAPK） signaling-mediated microglia activation. To clarify the pharmacodynamic basis and anti-stroke mechanism of DCQT， this article reviews the research progress in the treatment of stroke with DCQT in terms of clinical trials， pharmacodynamic material basis， safety evaluation， and mechanisms of absorbed components. This article summarizes 45 major phytochemical components of DCQT， 11 of which are currently confirmed absorbed components. Among them， emodin， rhein， chrysophanol， aloe-emodin， synephrine， hesperidin， naringin， magnolol， and honokiol can be used as quality markers （Q-markers） of DCQT. The mechanism of DCQT in treating stroke is complex， involving regulation of inflammatory responses， neuronal damage， oxidative stress， blood-brain barrier， brain-derived neurotrophic factor， and anti-platelet aggregation. This article helps to deeply understand the pharmacodynamic basis and mechanism of DCQT in treating stroke and provides a theoretical basis for the clinical application of DCQT in treating stroke and the development of stroke drugs.

Objective To investigate the predictive value of preoperative combined detection of neutrophil-to-lymphocyte ratio (NLR) and prothrombin time-international normalized ratio to albumin ratio (PTAR) for early abdominal infection after liver transplantation. Methods Clinical data of 287 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital, Affiliated to Capital Medical University, from January 2020 to April 2024 were retrospectively analyzed. The patients were divided into infection group (n=60) and non-infection group (n=227) based on whether abdominal infection occurred within 30 days after surgery. The distribution characteristics of pathogens and infection time in infected patients were analyzed. Spearman correlation analysis was used to assess the correlation between NLR, PTAR, Child-Pugh score and preoperative model for end-stage liver disease (MELD) score. Univariate and multivariate logistic regression analyses were performed to identify risk factors for abdominal infection. Receiver operating characteristic (ROC) curves were plotted for NLR, PTAR, and the combined prediction model to evaluate their predictive efficacy for abdominal infection after liver transplantation. Based on the cutoff value of the combined model, recipients were divided into low-risk and high-risk groups, and Kaplan-Meier analysis was used to compare the cumulative incidence of abdominal infection within 30 days after surgery between the two groups. Results Among the 287 recipients who underwent liver transplantation, 60 developed bacterial or fungal abdominal infections postoperatively. A total of 86 strains were isolated from infected patients, with Gram-negative bacteria accounting for 58%, Gram-positive bacteria for 36%, and fungi for 5%. Preoperative NLR and PTAR were positively correlated with Child-Pugh and MELD scores (all 1 > r > 0, P < 0.05). Logistic regression analysis showed that preoperative NLR, preoperative PTAR, postoperative ICU stay duration and postoperative biliary leakage were risk factors for abdominal infection within 30 days after surgery. The area under the curve (AUC) for NLR, PTAR, Child-Pugh score and MELD score were 0.771, 0.735, 0.650 and 0.741, respectively. The AUC for the combined NLR and PTAR prediction model was 0.824 (95% confidence interval: 0.763-0.885, P < 0.001), with a cutoff value of 0.168. Kaplan-Meier analysis showed that the cumulative incidence of abdominal infection within 30 days after surgery was lower in the low-risk group than in the high-risk group, with statistically significant difference (P < 0.001). Conclusions Preoperative NLR and PTAR are independent risk factors for abdominal infection within 30 days after liver transplantation. The combined prediction model of NLR and PTAR may effectively identify high-risk recipients for early abdominal infection after liver transplantation, providing basis for early intervention.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

ObjectiveTo compare the effectiveness and mechanism of Xiangzhu Fanggan Formula （香术防感方） by sniffing and nasal drops for preventing influenza A H1N1flu. MethodsFifty-six BALB/c mice were randomly divided into normal group， model group， zanamivir group， high-concentration sachet group， low-concentration sachet group， high-concentration nasal drops group， and low-concentration nasal drops group， with 8 mice in each group. In the low- and high-concentration sachet groups， 15 g and 30 g of Xiangzhu Fanggan Formula sachet were used for sniffing for 24 h per day； while in the low- and high-concentration nasal drops groups， nasal drops of Xiangzhu Fanggan Formula were given at a concentration of 0.11 and 0.22 g/ml， 20 μl each time， twice a day； in the zanamivir group， zanamivir was given at a concentration of 1.025 mg/ml of 20 μl each time， twice a day； in the normal group and the model group， nasal drops of normal saline were given at 20 μl each time， twice a day. Each group was given prophylactic intervention for 5 days. On day 5， 1 h after the administration of the drug， the mice in all groups except the normal group received 35 μl of 50 LD₅₀ A/PR/8/34/H1N1 viral solution as nasal drops to prepare influenza A H1N1 model mice. The body mass of the mice was recorded and the rate of change of body mass was calculated daily from day 5 to day 9 of the experiment， and the general status was observed. The mice were sampled on day 9， and the lung index and the inhibition rate of lung index were calculated； HE staining was used to detect pathological changes in lung tissues and to score lung tissue lesions； RT-qPCR was used to detect viral load in lung tissues； and ELISA was used to detect secretory immunoglobulin A （sIgA） and serum tumour necrosis factor α （TNF-α） and interleukin 2 （IL-2）， interleukin 6 （IL-6）， and interferon γ （IFN-γ） in the lavage fluid of the upper respiratory tract. ResultsOn days 7， 8 and 9 of the experiment， the rate of change in body mass of mice in the model group significantly lower than that in the normal group at the same time points （P＜0.05 or P＜0.01）. On days 8 and 9 of the experiment， the rate of change in body mass of mice in the zanamivir group and the high-concentration nasal drops group increased when compared with the model group （P＜0.05 or P＜0.01）. Compared with the normal group， mice in the model group had significantly higher lung index， lung tissue lesion score， lung tissue viral load， significantly higher serum TNF-α， IL-6， IL-2， IFN-γ levels， and significantly lower sIgA levels in the upper respiratory lavage fluid （P＜0.01）. Compared with the model group， the lung index and lung tissue viral load reduced， serum IFN-γ， TNF-α， IL-2， IL-6 levels reduced， and sIgA levels increased in the zanamivir group and the high-concentration nosal drops group （P＜0.05 or P＜0.01）； except for low-concentration sachet group， lung tissue lesion scores of the drug intervention groups reduced compared with those of the model group （P＜0.01）. Compared with the zanamivir group， the lung index increased in the low-concentration sachet group and the low- and high-concentration nasal drops groups， and the serum TNF-α and IL-2 levels increased in all Xiangzhu Fanggan Formula intervention groups （P＜0.05 or P＜0.01）. Compared with high-concentration nasal drops group， serum TNF-α and IFN-γ levels elevated in the high-concentration increased group， and lung tissue viral load elevated in the low-concentration nasal drops group （P＜0.05 or P＜0.01）. The lung index inhibition rate was 80.84% in the zanamivir group， 41.61% and 17.90% in the high- and low-concentration sachet groups， and 35.40% and 25.40% in the high- and low-concentration nasal drops groups， respectively. HE staining showed that the lung tissues of the model group showed thickening of alveolar septa， alveolar collapse， and infiltration of inflammatory cells； whereas， in each drug intervention group， the inflammation of the lung tissues of the mice and the damage reduced， and the most obvious improvement was in the zanamivir group and the high-concentration nasal drops group. ConclusionXiangzhu Fanggan Formula by sniffing and nasal drops could both prevent influenza A H1N1 virus infection， with antiviral and anti-inflammatory effects， also could improve the pathological damage of lung tissue， and improve the immunity of respiratory mucosa. The nasal drops may be better than sachets in inhibiting inflammatory response， especially the high-concentration nasal drops showed more effective.

Objective: To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder (PTSD), and to improve efficacy and patient compliance. Methods: In this study, we used ginger oil, a phytochemical with potential therapeutic properties, to prepare ginger oil patches. High-performance liquid chromatography (HPLC) was used to quantify the main active component of ginger oil, 6-gingerol. Transdermal absorption experiments were conducted to optimize the various pressure-sensitive adhesives and permeation enhancers, including their type and concentration. Subsequently, the ginger oil patches were optimized and subjected to content determination and property evaluations. A PTSD mouse model was established using the foot-shock method. The therapeutic effect of ginger oil patches on PTSD was assessed through pathological sections, behavioral tests, and the evaluation of biomarkers such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and melatonin (MT). Results: The results demonstrated that ginger oil patches exerted therapeutic effects against PTSD by inhibiting inflammatory responses and modulating MT and BDNF levels. Pharmacokinetic experiments revealed that ginger oil patches maintained a stable blood drug concentration for at least one day, addressing the rapid metabolism drawback of 6-gingerol and enhancing its therapeutic efficacy. Conclusions Ginger oil can be prepared as a transdermal drug patch that meets these requirements, and the bioavailability of the prepared patch is better than that of oral administration. It can improve PTSD with good patient compliance and ease of administration. Therefore, it is a promising therapeutic formulation for the treatment of PTSD.

Objective:To investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space(DTI-ALPS)in bipolar disorder Ⅰ(BD-Ⅰ).Methods:A total of 44 BD-Ⅰ patients(BD-Ⅰ group) admitted to the Affiliated Brain Hospital of Guangzhou Medical University from January 2012 to December 2017 were selected.In addition, totally 30 healthy controls (HC group) were recruited. The diffusion tensor image data were analyzed retrospectively, and along the perivascular space (ALPS) index was calculated. Hamilton anxiety scale (HAMA), 17-item Hamilton depression rating scale (HAMD-17), Young mania rating scale (YMRS) and global assessment function (GAF) were used to evaluate the severity of anxiety, depression, mania and social function respectively. SPSS 25.0 software was used for t-test, Z-test and chi-square test, and the differences in clinical data and DTI-ALPS index between the two groups were compared. The partial correlation test was used to analyze the correlations between DTI-ALPS index and the clinical indicators such as HAMA, HAMD-17, YMRS and GAF. Results:The DTI-ALPS indexes in left(1.69±0.17), right(1.44±0.15) and bilateral cerebral hemispheres(1.56±0.15) of BD-Ⅰ group were lower than those in HC group ((1.71±0.15), (1.46±0.13) and (1.58±0.12)), but the differences were not statistically significant ( t=-0.441, -0.545, -0.556, all P>0.05). After controlling for gender, age, years of education and course of disease, there were significant negative correlations between bilateral average DTI-ALPS index and somatic anxiety ( r=-0.334, P=0.038), as well as between right DTI-ALPS index and somatic anxiety( r=-0.349, P=0.030) in BD-Ⅰ group. Conclusion:The dysfunction of cerebral glymphatic system is not obvious in BD-Ⅰ patients, but their anxiety may be related to dysfunction cerebral glymphatic system.

Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Objective To explore differentially expressed endoplasmic reticulum stress-associated genes(ERSAGs)in aortic dissection(AD)and their correlations with immune cell infiltration to identify new therapeutic targets for AD.Methods Two AD mRNA expression datasets(GSE190635 and GSE98770)were downloaded from GEO database for analysis of differentially expressed genes between the aorta of AD patients and normal aorta using R software.ERSAGs dataset was downloaded from GeneCards website,and GeneMANIA database was used to analyze the protein-protein interaction network of the differentially expressed ERSAGs and the proteins interacting with these genes.Based on GSE98770 dataset we analyzed the distributions of 22 immune cells within the aortic wall of AD patients using CIBERSORT package of R software.Surgical aortic wall specimens were obtained from 10 AD patients and 10 non-AD patients for detecting AGER mRNA expression using qRT-PCR,and the upstream transcriptional factors,miRNAs,and chemicals targeting AGER were analyzed using the TRRUST database and NetworkAnalyst database.Results Bioinformatic analysis suggested significant differential expression of AGER in AD,which interacted with 20 proteins involved in pattern recognition receptor signaling pathway,positive regulation of DNA-binding transcription factor activity,myeloid leukocyte migration,leukocyte migration,and regulation of the I-κB kinase/NF-κB signaling.In AD,AGER expression level was positively correlated with Treg cell abundance(r=0.59,P<0.05).The results of qRT-PCR demonstrated significantly lower expression of AGER mRNA in AD than in non-AD patients(1.00±0.30 vs 1.76±0.68,P<0.05).ROC curve analysis showed that at the cut-off value of 1.335,AGER had an AUC of 0.86(95%CI:0.67-1.00,P=0.0073)for predicting AD.Three transcriptional factors,3 miRNAs,and 27 chemicals were predicted in the AGER regulatory network.Conclusion AGER is lowly expressed in the aorta of AD patients and may influence the occurrence of AD through Treg cells.

Objective:To investigate the impact of elevated glucose-induced RNA oxidation on pancreatic β-cell function, activity, and underlying molecular mechanisms.Methods:Rat pancreatic islet β-cell tumour INS-1 cells were cultured in vitro and subjected to nucleic acid oxidation assessment using isotope dilution ultra-high performance liquid tandem mass spectrometry(ID LC MS/MS)following high glucose exposure.In vitro simulation of increased RNA oxidation in INS-1 cells was achieved using 8-oxoguanosine-5'-triphosphate(8-oxoGTP).Cell proliferation was evaluated through CCK-8 assay, apoptosis was measured via flow cytometry, and gene expression of insulin(INS), pancreatic-duodenal homologous cassette 1(PDX1), cysteine-aspartate proteinase 3(Casp3), and cysteine aspartate protease 6(Casp6)was analyzed at the mRNA level.Additionally, whole transcriptome sequencing was performed to elucidate the molecular mechanisms underlying the impact of RNA oxidation on INS-1 cells.Results:Elevated glucose levels induced an increase in RNA oxidation within INS-1 cells.This heightened RNA oxidation led to the inhibition of INS-1 cell proliferation, a reduction in mRNA levels of INS and PDX1 genes, and the promotion of apoptosis-related casp3 and casp6 gene mRNA synthesis.Transcriptome sequencing analysis unveiled that the elevated RNA oxidation caused differential expression of mRNA, lncRNA, miRNA, and circRNA in INS-1 cells.This included a significant down-regulation of transcription factors such as Mafa, Pdx1, Pax6, and Mnx1, alongside an up-regulation of various miRNAs like rno-miR-124-3p, rno-miR-133a-3p, rno-miR-3120, rno-miR-212-3p, and rno-miR-7a-2-3p.These molecular changes contributed to the altered expression of associated lncRNAs, ultimately hindering insulin synthesis and secretion, as well as β-cell proliferation.Conclusions:Increased RNA oxidation down-regulates the levels of key β-cell transcription factor mRNAs, contributes to the differential expression of related non-coding RNAs(ncRNAs), particularly lncRNAs, impacts β-cell insulin synthesis and secretion, hinders cell proliferation, and serves as a significant factor in β-cell dysfunction and decreased activity in type 2 diabetes mellitus(T2DM).