Precancerous lesions of gastric cancer （PLGC） are a group of pathological changes caused by abnormalities in the structure， morphology， and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific， PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly， the incidence of this disease is increasing year by year， which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex， involving inflammatory microenvironment， bile reflux， glycolysis， autophagy， and apoptosis. Currently， PLGC is mainly treated with anti-inflammatory and endoscopic therapies， which are difficult to curb the development of PLGC. Therefore， seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine （TCM）， characterized by treatment based on syndrome differentiation and a holistic view， exerts effects via multiple pathways， mechanisms， and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）， Wnt/β-catenin， Sonic Hedgehog， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， hypoxia-inducible factor-1α （HIF-1α）， neurogenic locus notch homolog protein （Notch）， nuclear factor E₂-related factor 2 （Nrf2） and other signaling pathways. By targeting these pathways， TCM can inhibit aerobic glycolysis， reduce oxidative stress， repair the inflammatory microenvironment， regulate cellular autophagy， and promote vascular normalization， thereby delaying or reversing PLGC. However， few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad， this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC， with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.

Objective: To explore the relationship between stigma and mental resilience in adolescent epilepsy patients and associated factors, so as to provide reference for future psychological intervention in adolescent patients with epilepsy. Methods: A total of 295 adolescent patients with epilepsy from Wuhan Mental Health Center were enrolled as participants from February 2021 to October 2024. The stigma was evaluated by Kilifi Stigma Scale for Epilepsy (KSSE), and psychological resilience was evaluated by Connor-Davidson Resilience Scale (CD-RISC). Associated factors of stigma and psychological resilience in adolescent patients with epilepsy were analyzed by multivariate Logistic regression analysis. Results: In the adolescent patients with epilepsy, KSSE score was (10.90±4.13) points, with 138 cases (46.78%) at low level, 154 cases (52.20%) at moderate level and 3 cases (1.02%) at high level. CD-RISC score was (50.19±5.97) points, there were 170 cases (57.63%) at low level and 125 cases (42.37%) at high level. Multivariate Logistic regression analysis showed that disease course >3 years ( OR =2.22), family history of epilepsy ( OR = 4.18) , monthly family income ≤5 000 yuan ( OR =2.05), single parent family ( OR =2.46) and middle and high stigma level ( OR = 1.72) had a higher risk on low level of mental resilience ( P <0.05). The course of disease >3 years ( OR =2.20), family history of epilepsy ( OR =3.54), general seizure ( OR =2.12), monthly family income ≤5 000 yuan ( OR =2.70), low level of mental resilience ( OR =2.03) of adolescent epilepsy patients showed a high risk on moderate high level of stigma ( P <0.05). Conclusions The stigma level is higher, while psychological resilience is lower in adolescent patients with epilepsy. Clinically, targeted intervention should be implemented based on related factors such as stigma in addescent patients with epilepsy.

Objective:To investigate the potential diagnostic value of peripheral blood soluble programmed cell death protein 1 (sPD-1) and soluble programmed cell death protein ligand 1 (sPD-L1) in acute rejection (AR) following liver transplantation using a rat model.Methods:A rat liver transplantation AR model was established, with the AR group (Lewis→BN) set as the experimental group (n=6) and the non-AR group (BN→BN) as the control group (n=6). Peripheral blood sPD-1 and sPD-L1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA) at 1 day before transplantation and at 1, 3, and 7 days postoperatively. On postoperative day 7, the expression levels of PD-1 and PD-L1 in liver tissues were detected by immunohistochemistry (IHC). Independent samples t-test and repeated measures ANOVA were used to compare the results between the two groups. Pearson correlation analysis was conducted to evaluate the relationship between sPD-1, sPD-L1, the sPD-1/sPD-L1 ratio, and the rejection activity index.Results:On postoperative day 7, the experimental group exhibited significantly higher peripheral sPD-1 levels (218.59±36.88 vs. 164.95±15.82 ng/L) and a higher sPD-1/sPD-L1 ratio (0.44±0.12 vs. 0.36±0.07), but lower sPD-L1 levels (379.56±73.41 vs. 423.64±96.55 ng/L) compared to the control group (all P<0.05). Correlation analysis revealed a significant positive correlation between sPD-1 levels and the rejection activity index ( r=0.680, P<0.05), as well as between the sPD-1/sPD-L1 ratio and the rejection activity index ( r=0.795, P<0.01), while no correlation was observed between sPD-L1 levels and the rejection activity index. IHC demonstrated positive PD-1 and PD-L1 expression in the liver tissues of the experimental group, whereas the control group showed negative expression. Conclusion:Peripheral blood sPD-1 levels and the sPD-1/sPD-L1 ratio are significantly associated with AR after liver transplantation in rats, suggesting their potential as biomarkers for diagnosing AR in liver transplant recipients.

Objective:To investigate the potential diagnostic value of peripheral blood soluble programmed cell death protein 1 (sPD-1) and soluble programmed cell death protein ligand 1 (sPD-L1) in acute rejection (AR) following liver transplantation using a rat model.Methods:A rat liver transplantation AR model was established, with the AR group (Lewis→BN) set as the experimental group (n=6) and the non-AR group (BN→BN) as the control group (n=6). Peripheral blood sPD-1 and sPD-L1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA) at 1 day before transplantation and at 1, 3, and 7 days postoperatively. On postoperative day 7, the expression levels of PD-1 and PD-L1 in liver tissues were detected by immunohistochemistry (IHC). Independent samples t-test and repeated measures ANOVA were used to compare the results between the two groups. Pearson correlation analysis was conducted to evaluate the relationship between sPD-1, sPD-L1, the sPD-1/sPD-L1 ratio, and the rejection activity index.Results:On postoperative day 7, the experimental group exhibited significantly higher peripheral sPD-1 levels (218.59±36.88 vs. 164.95±15.82 ng/L) and a higher sPD-1/sPD-L1 ratio (0.44±0.12 vs. 0.36±0.07), but lower sPD-L1 levels (379.56±73.41 vs. 423.64±96.55 ng/L) compared to the control group (all P<0.05). Correlation analysis revealed a significant positive correlation between sPD-1 levels and the rejection activity index ( r=0.680, P<0.05), as well as between the sPD-1/sPD-L1 ratio and the rejection activity index ( r=0.795, P<0.01), while no correlation was observed between sPD-L1 levels and the rejection activity index. IHC demonstrated positive PD-1 and PD-L1 expression in the liver tissues of the experimental group, whereas the control group showed negative expression. Conclusion:Peripheral blood sPD-1 levels and the sPD-1/sPD-L1 ratio are significantly associated with AR after liver transplantation in rats, suggesting their potential as biomarkers for diagnosing AR in liver transplant recipients.

Gastric cancer （GC） is one of the most common cancers in the world， with hidden symptoms， complex pathogenesis， high morbidity， high mortality， and poor prognosis. As one of the classical apoptosis pathways， mitochondrial apoptosis has been widely described in the apoptosis escape by GC cells. Mitochondrial apoptosis can regulate the proliferation， invasion， and metastasis of GC cells via oxidative stress， cell cycle， mitochondrial membrane potential， mitochondrial translocation and other mechanisms， and it is one of the potential targets of traditional Chinese medicine （TCM） intervention to restore the mitochondrial function in GC. The theory of spleen-mitochondria in correlation explains that spleen deficiency and cancer toxin are the root causes of mitochondrial apoptosis. Accordingly， the TCM treatment should follow the basic principle of invigorating spleen to restore healthy Qi and removing cancer toxin to eliminate the root cause. Mitochondrial apoptosis can be promoted by inhibiting oxidative stress， promoting cell cycle arrest， and reducing mitochondrial membrane potential. This therapy can improve the energy metabolism， restore the mitochondrial structure and function， and prevent the occurrence and development of GC， with mild side effects and low drug resistance. However， the mechanism of mitochondrial apoptosis in GC and the target of TCM intervention in GC have not been systematically reviewed. Therefore， this paper systematically summarized the effects of mitochondrial apoptosis on the occurrence and development of GC and the role of TCM in the treatment of GC by intervening in mitochondrial apoptosis， aiming to provide a theoretical reference for the treatment and further research of GC.

Interferon regulatory factor 1(IRF-1)is a member of the IRF family.It is the first transcription factor to be identified that could bind to the interferon-stimulated response element(ISRE)on the target gene and displays crucial roles in the interferon-induced signals and pathways.IRF-1,as an important medium,has all of the advantages of full cell cycle regulation,cell death signaling transduction,and reinforcing immune surveillance,which are well documented.Current studies indicate that IRF-1 is of vital importance to the occurrence and evolution of multifarious liver diseases,including but not limited to inhibiting the replication of the hepatitis virus(A/B/C/E),alleviating the progression of liver fibrosis,and aggravating hepatic ischemia-reperfusion injury(HIRI).The tumor suppression of IRF-1 is related to the clinical characteristics of liver cancer patients,which makes it a potential indicator for predicting the prognosis and recurrence of liver cancer;additionally,the latest studies have revealed other effects of IRF-1 such as protection against alcoholic/non-alcoholic fatty liver disease(AFLD/NAFLD),cholangiocarcinoma suppression,and uncommon traits in other liver diseases that had previously received little attention.Intriguingly,several compounds and drugs have featured a protective function in specific liver disease models in which there is significant involvement of the IRF-1 signal.In this paper,we hope to propose a prospective research basis upon which to help decipher translational medicine applications of IRF-1 in liver disease treatment.

Objective:To establish and validate a fluorescence PCR with internal positive control for rapid Mycoplasma detection. Methods:A fluorescence PCR with internal positive control for Mycoplasma detection was developed and verified for its specificity, limit of detection, and robustness. A sample of fever with thrombocytopenia syndrome (SFTSV) virus strains was tested with this method, and the result was compared with those of culture method and indicator cell culture method. Results:The established fluorescence PCR had good specificity and could amplify 11 kinds of plasmids containing Mycoplasma 16S rRNA gene with high efficiency. There was no cross reaction with the genomic DNAs of Clostridium sporogenes, Clostridium acetobutylicum, Lactobacillus acidophilus, Streptococcus pneumoniae, Bacillus subtilis, Staphylococcus aureus, Salmonella enteritidis, Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger, Candida albicans, Vero cells, RD cells, and SF9 cells. The amplification efficiency of the internal positive control was basically consistent with that of the target gene of Mycoplasma, suggesting that the internal positive control could be used to detect the presence of PCR inhibitors. The sensitivity of the established method was high, and the detection limit was 10 colony-forming unit (CFU)/ml for Mycoplasma fermentans, 5 CFU/ml for Mycoplasma arginine, 5 CFU/ml for Mycoplasma gallisepticum, 5 CFU/ml for Mycoplasma hyorhinis, 5 CFU/ml for Acholeplasma laidlawii, 5 CFU/ml for Mycoplasma orale, 5 CFU/ml for Mycoplasma pneumoniae, 5 CFU/ml for Mycoplasma synoviae, and 1 CFU/ml for Spiroplasma citri by 7500 Fast real-time PCR system. At the detection limit of each species, there was no significant difference in the positive detection rate using different thermal cycler types. The established fluorescence PCR, culture method, and indicator cell culture were performed to detect Mycoplasma in the sample of SFTSV virus strains, and the results all showed Mycoplasma contamination. Conclusions:The established fluorescence PCR has high specificity, sensitivity, and robustness, and can be used as an alternative method for rapid detection of Mycoplasma.

Objective To evaluate the role of preoperative serological indexes in predicting long-term survival and tumor recurrence of hepatocellular carcinoma (HCC) patients after liver transplantation, aiming to explore its significance in expanding the Milan criteria. Methods Clinical data of 669 recipients undergoing liver transplantation for HCC were retrospectively analyzed. The optimal cut-off value was calculated by the receiver operating characteristic (ROC) curve. The risk factors affecting the overall survival and recurrence-free survival rates of HCC patients after liver transplantation were identified by univariate and multivariate regression analyses. The correlation between preoperative serum liver enzymes and pathological characteristics in HCC patients was analyzed. The predictive values of alpha-fetoprotein (AFP) combined with γ -glutamyl transferase (GGT) and different liver transplant criteria for the survival and recurrence of HCC patients after liver transplantation were compared. Results Exceeded Milan criteria, total tumor diameter (TTD) > 8 cm, AFP > 200 ng/mL and GGT > 84 U/L were the independent risk factors for the overall survival and recurrence-free survival rates of HCC patients after liver transplantation (all P < 0.05). Correlation analysis showed that preoperative serum GGT level was correlated with TTD, number of tumor, venous invasion, microsatellite lesions, capsular invasion, tumor, node, metastasis (TNM) stage, Child-Pugh score and exceeded Milan criteria (all P < 0.05). Milan-AFP-GGT-TTD (M-AGT) criteria were proposed by combining Milan criteria, TTD with serum liver enzyme indexes (AFP and GGT). The 5-year overall survival and recurrence-free survival rates of HCC recipients who met the M-AGT criteria (111 cases of exceeded Milan criteria) were significantly higher than those who met Hangzhou criteria (both P < 0.05), whereas had no significant difference from their counterparts who met the University of California at San Francisco (UCSF) criteria (both P > 0.05). Conclusions Preoperative serological indexes of AFP and GGT could effectively predict the long-term survival and tumor recurrence of HCC patients after liver transplantation. Establishing the M-AGT criteria based on serological indexes contributes to expanding the Milan criteria, which is convenient and feasible.

The aim of this study was to identify whether periodontitis induces gut microbiota dysbiosis via invasion by salivary microbes. First, faecal and salivary samples were collected from periodontally healthy participants (PH group, n = 16) and patients with severe periodontitis (SP group, n = 21) and analysed by 16S ribosomal RNA sequencing. Significant differences were observed in both the faecal and salivary microbiota between the PH and SP groups. Notably, more saliva-sourced microbes were observed in the faecal samples of the SP group. Then, the remaining salivary microbes were transplanted into C57BL6/J mice (the C-PH group and the C-SP group), and it was found that the composition of the gut microbiota of the C-SP group was significantly different from that of the C-PH group, with Porphyromonadaceae and Fusobacterium being significantly enriched in the C-SP group. In the colon, the C-SP group showed significantly reduced crypt depth and zonula occludens-1 expression. The mRNA expression levels of pro-inflammatory cytokines, chemokines and tight junction proteins were significantly higher in the C-SP group. To further investigate whether salivary bacteria could persist in the intestine, the salivary microbiota was stained with carboxyfluorescein diacetate succinimidyl ester and transplanted into mice. We found that salivary microbes from both the PH group and the SP group could persist in the gut for at least 24 h. Thus, our data demonstrate that periodontitis may induce gut microbiota dysbiosis through the influx of salivary microbes.
Animals ; Dysbiosis ; Gastrointestinal Microbiome ; Humans ; Mice ; Mice, Inbred C57BL ; Microbiota ; Periodontitis ; RNA, Ribosomal, 16S/metabolism*

Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely