ObjectiveTo investigate the mechanism of action of Jiedu Huayu granules in improving liver injury in mice with acute liver failure （ALF） by observing its effect on a mouse model of ALF after prophylactic administration， and to provide a basis for clinical medication. MethodsA total of 60 specific pathogen-free male C57BL/6J mice were divided into normal group， model group， Jiedu Huayu granules group （JDHY group）， and farnesoid X receptor （FXR） agonist （GW4064） group using a random number table， with 15 mice in each group. The model of ALF was induced by a single intraperitoneal injection of D-galactosamine combined with lipopolysaccharide. The mice in the JDHY group were given prophylactic administration of 0.3 g/mL drug solution of Jiedu Huayu granules by gavage for 3 days before modeling， those in the normal group and the model group were given 0.9% NaCl solution by gavage， and those in the GW4064 group were given intraperitoneal injection of GW4064 for 3 consecutive days before modeling. The mice were sacrificed after modeling， and serum and liver tissue samples were collected. A veterinary automatic biochemical analyzer was used to measure the serum levels of total bilirubin （TBil）， total bile acids （TBA）， gamma-glutamyl transferase （GGT）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in mice from each group； HE staining was used to observe liver pathological changes； RT-PCR was used to measure the mRNA expression levels of FXR， fibroblast growth factor 15 （FGF15）， fibroblast growth factor receptor 4 （FGFR4）， small heterodimer partner （SHP）， and bile salt export pump （BSEP） in mice， and Western blot was used to measure the protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP. A one-way analysis of variance was used for comparison between groups， and the Dunett method was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in the serum levels of TBil， ALT， AST， TBA， and GGT （all P<0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant reductions in the serum levels of TBil， ALT， AST， TBA， and GGT （all P <0.01）. HE staining showed that compared with the model group， the JDHY group and the GW4064 group had milder pathological injury， a reduction in the area of hepatocyte necrosis， and alleviation of cellular swelling and edema. Compared with the normal group， the model group had significant reductions in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant increases in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.05）. ConclusionJiedu Huayu granules may alleviate liver injury in mice with ALF through the FXR/SHP axis.

This study examined the effect of islet macrophages on β-cell function changes during type 2 diabetes mellitus (T2DM) progression based on the traditional Chinese medicine theory that " moderate fire generating qi, hyperactive fire consuming qi" . T2DM is closely associated with chronic low-grade inflammation, with islet macrophages playing a central role in this process. Under physiological conditions, islet macrophages secrete anti-inflammatory and growth factors to regulate the immune response, promote cell proliferation, and support islet β-cell survival and function, reflecting the concept of " moderate fire generating qi" . However, during the pathological process of T2DM, islet macrophages become over-activated and dysfunctional, secreting large amounts of pro-inflammatory factors that trigger severe inflammatory responses and oxidative stress. This process damages islet β-cells, disrupts the islet microenvironment and blood supply, exacerbates local inflammation and structural damage, and worsens the survival environment of β-cells. Ultimately, this leads to fewer β-cells and function loss, aligning with the " hyperactive fire consuming qi" theory, where excessive fire depletes qi and blood. This study enhances the understanding and application of traditional Chinese medicine theories in modern medicine, offering a new perspective on T2DM prevention and treatment. Regulating islet macrophage function and reducing their pro-inflammatory responses may become key strategies for preserving β-cell function and slowing T2DM progression.

Hepatic encephalopathy （HE） is a common complication of severe liver disease in the end stage， and it is urgently needed to improve the rate of effective treatment and clarify the pathogenesis of HE. The liver is a crucial hub for immune regulation， and disruption of immune homeostasis is a key factor in the pathological mechanisms of HE. As the main metabolites of intestinal flora， short-chain fatty acids （SCFAs） play a vital role in the biological processes of both innate and adaptive immunity and can regulate the proliferation and differentiation of immune cells maintain the homeostasis of intestinal microenvironment and the integrity of barrier function. Studies have shown that SCFAs participate in bidirectional and dynamic interactions with the liver-gut-brain axis through immunomodulatory pathways， thereby playing an important role in the diagnosis， treatment， and prognostic evaluation of HE. Starting from the immunoregulatory effect of SCFAs， this article summarizes and analyzes the crosstalk relationship between SCFAs and the liver-gut-brain axis and the significance of SCFAs in the diagnosis and treatment of HE， in order to provide new ideas for optimizing clinical prevention and treatment strategies.

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

Hepatocellular carcinoma （HCC） is a malignant tumor with high incidence and mortality rates worldwide. Recent studies have shown that neutrophil extracellular traps （NETs） play an important role in the development， progression， and immune escape of HCC. NETs are released by neutrophils and mainly consist of DNA， histones， and antimicrobial molecules， and in addition to immune defense， they are also involved in the initiation， metastasis， and thrombosis of HCC. This article elaborates on the formation and regulatory mechanisms of NETs， explores their potential mechanisms in the initiation， metastasis， immune escape， and thrombosis of HCC， and discusses the prospect of NETs as a target for the diagnosis and treatment of HCC， in order to provide new ideas for the precise treatment of HCC in the future and promote the early diagnosis and effective treatment of HCC.

OBJECTIVE Melatonin(MEL),a natural hormone with broad-spectrum anticancer effects,has been shown to potentiate the therapeutic outcomes of conventional chemotherapy.This study aims to investigate the combined effects of Doxorubicin(DOX)and MEL on head and neck squamous cell carcinoma(HNSCC)cell lines.METHODS The effects of MEL and DOX on cell proliferation in HNSCC cell lines TU686 and CAL-27 were assessed using the MTT assay.The effects of MEL and DOX on reactive oxygen species(ROS)expression levels in HNSCC cell lines were detected using DCFH-DA fluorescent probe.The effects of MEL and DOX on 8-hydroxy-2′-deoxyguanosine(8-oxodG)levels in HNSCC cell lines were measured by enzyme-linked immunosorbent assay(ELISA).The effects of MEL and DOX on γ-H2AX protein levels in HNSCC cell lines were analyzed via Western blot.The effects of MEL and DOX on antioxidant enzymes levels in HNSCC cell lines were evaluated based on spectrophotometry.The effects of MEL and DOX on cell apoptosis in HNSCC cell lines were detected using an ELISA cell death detection kit.RESULTS The MTT assay revealed that MEL significantly enhanced the cytotoxic effects of DOX in HNSCC cell lines(tTU686=13.51,tCAL-27=17.580,all P<0.05).The combination of MEL and DOX markedly increased intracellular ROS levels(FTU686=89.984,FCAL-27=102.853,all P<0.05),while the expression of antioxidant enzymes was significantly reduced(TU686:the F values of CAT,GPx,GR,GST and SOD are 176.035,34.662,20.260,120.105 and 184.254,all P<0.05;CAL-27:the F values are 96.801,177.398,97.849,102.750 and 186.608 respectively,all P<0.05).Furthermore,this combination treatment significantly elevated the expression levels of 8-oxodG(FTU686=200.078,FCAL-27=663.982,all P<0.05)and γ-H2AX(FTU686=192.500,FCAL-27=285.700,all P<0.01)in HNSCC cell lines.Additionally,compared to single-agent treatment,MEL significantly enhanced DOX-induced apoptosis in HNSCC cell lines(FTU686=2718.253,FCAL-27=5185.334,all P<0.01).CONCLUSION The combination of MEL and DOX can enhance cytotoxic effects on HNSCC cell lines,increase intracellular ROS levels,induce DNA oxidative damage,and impair cellular antioxidant defense capacity,thereby effectively promoting HNSCC cell apoptosis.This combination may represent a novel therapeutic approach to improve clinical outcomes in HNSCC.

Objective:To evaluate the clinical efficacy of Xiaoxuming Decoction combined with conventional Western medicine therapy in the treatment of patients with ischemic stroke in the recovery period.Methods:A randomized controlled clinical study was conducted. A total of the 118 patients with wind phlegm obstructing collaterlas syndrome during the recovery period of ischemic stroke in our hospital from September 2023 to July 2024 were selected as the observation subjects. They were divided into two groups using a random number table method, with 59 patients in each group. The control group was treated with conventional Western medicine therapy, while the TCM group was treated with modified Xiaoxuming Decoction on the basis of the control group. Both groups were treated for 2 months and followed up for 1 month. TCM syndrome scoring was performed before and after treatment, Barthel Index was used to evaluate daily living ability, and carotid artery ultrasound detector was used to evaluate the stability of carotid vascular plaques. Inter group comparisons were performed using t test, χ2 test, or repeated measures analysis of variance (RM-ANOVA). Results:RM-ANOVA showed that the time effect and inter group effect of TCM syndrome integration in the TCM group were significantly different from those in the control group ( Ftime=55.56, Ptime<0.001); Fbetween=18.94, Pbetween<0.001); there was no statistical significance in the interaction effect compared to the control group ( Finteraction=0.24, Pinteraction=0.866); the time effect, inter group effect, and interaction effect of Barthel Index in the TCM group were significantly different from those in the control group ( Ftime=44.57, Ptime<0.001); Fbetween=18.94, Pbetween<0.001; Finteraction=7.45, Pinteraction<0.001). The number of patients with unstable plaques in the TCM group after 3 months of treatment was lower than that in the control group ( χ2=4.52, P=0.033). Conclusion:The combination of modified Xiaoxuming Decoction and conventional Western medicine therapy can effectively improve the clinical symptoms and daily living ability of patients in the recovery period of ischemic stroke, improve the stability of cervical vascular plaques, and the clinical efficacy becomes more significant over time.

Objective To explore the public's cognition and attitude towards general medicine,general practitioners,and pre-hospital first-aid knowledge in Ludian County,Yunnan Province,to find out the training and learning methods that are more acceptable to the public for this kind of related knowledge,and to propose targeted solutions.Methods A complete random sampling survey was conducted among the nucleic acid collection office at the gate of the vegetable market from October 15,2022,to December 30,2022,and the outpatient clinic of Wenping Street Health Center from January 1,2023,to February 28,2023,by using electronic questionnaire and paper questionnaire.Results Nearly 50%of the people in Ludian County of Yunnan Province lack the knowledge of general medicine and pre-hospital emergency care,especially the knowledge of electrical defibrillation.People with higher education and the medical profession have a higher understanding of general medicine,and people with a higher understanding of general medicine are more willing to participate in pre-hospital emergency care.The average Ridit value is:very familiar with general medicine(0.774)>Knowledge of some general practices(0.565)>Never heard of general practice(0.400).The higher education level and the more comprehensive understanding of general medicine had a positive impact on participation in pre-hospital emergency care,with B values of 0.624 and 0.619,OR 95%CI of 1.867(1.544～2.257)and 1.857(1.298～2.657),respectively.Taking medical staff as a reference,the B value of medical students was = 0.942,P = 0.234,the difference was not significant,and the B value of non-medical professional population was all less than 0,the effect is negative.In addition,most people have a positive attitude towards learning pre-hospital first aid,and more than 70%of people are willing to learn and train related knowledge of pre-hospital first aid.Conclusions People in urban areas of Ludian County,Yunnan Province have poor understanding of general practice,low recognition of general practitioners,low demand for general practitioners,and lack of awareness of the importance of pre-hospital emergency treatment.Because of the cognitive differences among different groups,it is necessary to conduct specific training for different groups.

Objective:To investigate the role of TcpC, a virulence factor of uropathogenic Escherichia coli (UPEC), in immune evasion, and analyze its related pathogenic mechanism. Methods:C57BL/6 mice were injected with 10 9 colony-forming unit of wild-type (CFT073 wt) or tcpc gene-knockout (CFT073 Δ tcpc) UPEC CFT073 strains from urethra into bladder to construct a mouse model of pyelonephritis. These mice were sacrificed 5 d after infection and their kidneys were taken to observe the gross pathological changes. Hematoxylin-eosin staining was used to observe histopathological changes in kidney tissues and immunohistochemistry was performed to locate TcpC in kidney tissues. The bacterial loads in urine samples of UPEC infected-mice were counted by ten-fold dilution method, and the presence of tcpc gene in the genomic DNA of bacteria from CFT073-infected mouse kidney or urine samples was measured by PCR. The expression of TcpC at mRNA level was detected by qRT-PCR after infecting dendritic cells with CFT073 wt strains. The influences of UPEC infection on the activation of NF-κB signaling pathway and the secretion of proinflammatory factors by dendritic cells were analyzed by Western blot and ELISA, respectively. The viability of UPEC strains in dendritic cells were observed by laser confocal microscope. Results:Compared with the CFT073 Δ tcpc group, the mice in the CFT073 wt group had obvious abscess in the kidneys as well as massive neutrophil infiltration and abundant TcpC in kidney tissues. The bacterial loads in the urine of CFT073 wt-infected mice were significantly higher than those in the urine of CFT073 Δ tcpc mice. PCR results showed that tcpc gene was successfully amplified from mouse kidney and urine samples. Increased expression of TcpC at both mRNA and protein levels was detected in CFT073 wt-infected dendritic cells. CFT073 wt infection inhibited the phosphorylation of NF-κB p50 and the production of proinflammatory factors in dendritic cells. TcpC promoted the survival of CFT073 wt in dendritic cells. Conclusions:TcpC expression increases significantly during CFT073 wt infection or in mice with CFT073 wt-induced pyelonephritis. It promotes the survival of CFT073 wt in dendritic cells by inhibiting the activation of NF-κB signaling pathway and reducing the secretion of pro-inflammatory cytokines. TcpC is involved in the pathogenesis of UPEC and immune evasion.

Objective: To evaluate the efficacy and safety of Jiawei Simiao powder (JWSMP) combined with celecoxib for the treatment of acute gouty arthritis by conducting a meta-analysis of randomized controlled trials (RCTs). Methods: The Chinese National Knowledge Infrastructure Databases, Chinese Scientific Journal Database, Wanfang, Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched from inception until December 2023. Continuous variables were analyzed using the mean difference (MD) for analysis, and dichotomous variables were used as risk ratios. Data with similar characteristics were pooled for meta-analysis, and heterogeneity was assessed using I2. The Cochrane Handbook was used to assess the risk of bias and quality. RevMan 5.3 software was used to perform the meta-analysis. Results: Thirteen RCTs involving 1007 patients were included in the study. The quality of the included studies was low (unclear randomization processes and insufficient blinding reporting). The group receiving JWSMP combined with celecoxib showed significantly lower levels of serum uric acid (SUA, MD = −66.32, 95% confidence interval (CI): −80.97 to −51.67, P < .001), erythrocyte sedimentation rate (ESR, MD = −6.05, 95% CI: −8.29 to −3.82, P < .001), C-reactive protein (CRP, MD = −7.39, 95% CI: −11.15, −3.63, P < .001), and joint pain score (VAS score, MD = −2.14, 95% CI: −2.4 to −1.88, P < .001) compared to celecoxib alone. Additionally, the JWSMP combined group had a higher total effective rate (risk ratio = 1.22, 95% CI: 1.14 to 1.29, P < .001) and fewer adverse compared to celecoxib alone. Conclusions JWSMP combined with celecoxib is more effective than celecoxib alone in improving the total efficacy rate, alleviating joint pain, and improving SUA, ESR, and CRP levels. JWSMP also reduced the occurrence of adverse events caused by celecoxib. However, the quality of the included studies was low, highlighting the need for further high-quality research with larger sample sizes and robust methodologies, such as double-blind randomization, to confirm these findings.