Acute liver failure (ALF) is lack of broadly approved therapeutic strategy except liver transplantation. As a glycogen metabolic intermediate, UDP-glucose (UDP-G) has been considered to accelerate liver repairment. Nevertheless, the role of UDP-G and its receptor P2Y purinoceptor 14 (P2Y₁₄R) in ALF remains unknown. The present study aims to investigate the role and underlying mechanisms of UDP-G/P2Y₁₄R axis in ALF. In this study, hepatic P2Y₁₄R is significantly increased in TAA-induced and partial hepatectomy-induced ALF, while knockout of whole-body P2Y₁₄R aggravates liver failure, manifested by inhibiting β-Catenin-mediated liver regeneration. Consistently, P2Y₁₄R deficiency exhibits impaired liver regeneration in mice suffer partial hepatectomy. Importantly, only hepatocellular specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Alb ^cre/+ ) mice shows a similar phenomenon, rather than stellate cell specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Lrat ^cre/+ ) mice. Mechanistically, P2Y₁₄R induction regulates methylation of Dact-2 through CREB/DNMT3b signals in hepatocytes, subsequently inhibiting the expression of Dact-2 which is a stabilizer of β-Catenin degradation complex, leading to the activation of β-Catenin -mediated liver regeneration. Interestingly, the administration of exogenous UDP-G can accelerate liver regeneration and liver function recovery after partial hepatectomy in hepatocellular carcinoma mice. Together, the findings propose an unrecognized role of P2Y₁₄R in ALF and provide an effective adjuvant strategy for treatment of ALF.

ObjectiveTo investigate the potential mechanisms of Zingiberis Rhizoma in treating inflammatory bowel disease （IBD） by integrating network pharmacology with in vitro and in vivo experiments. MethodsTraditional Chinese Medicine Systems Pharmacology Database And Analysis Platform （TCMSP）， Traditional Chinese Medicine Integrated Database （TCMID） Database were used to obtain the active component targets of Zingiberis Rhizoma. GeneCards was used to obtain the IBD targets. DAVID was used to perform Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses on core targets. Cytoscape 3.10.2 was used to establish the "active component-disease target-signaling pathway" interaction network. Mice were randomly assigned to control， model， and Zingiberis Rhizoma （400 mg·kg^-1） groups. An IBD model was induced via dextran sulfate sodium （DSS）. The colonic tissue was collected post-treatment to assess histology， expression of Ly6C⁺ monocytes/macrophages， and mRNA levels of Toll-like receptor 4 （TLR4）， and inflammatory cytokines. The effect of Zingiberis Rhizoma aqueous extract on RAW264.7 cell viability was evaluated. Furthermore， the effects of the extract at 100， 10， and 1 mg·L^-1 on LPS-induced differentiation of RAW264.7 cells into Ly6C^hi monocytes/macrophages， mRNA levels of TLR4 and inflammatory cytokines， and protein levels of factors in the TLR4/mitogen-activated protein kinase （MAPK） signaling pathway. ResultsA total of 241 targets were identified for Zingiberis Rhizoma and 6 787 for IBD， with 122 shared targets among Zingiberis Rhizoma， ulcerative colitis （UC）， and Crohn's disease （CD）. The enrichment analyses yielded 297 GO terms and 88 KEGG pathways. Associations were noted between Zingiberis Rhizoma's active component targets and IBD targets. In vivo experiments： Compared with the control group， the model group showed decreased body weight and disease activity index （DAI）（P<0.01）， shortened colon length， damaged mucosal epithelium with inflammatory cell infiltration， raised pathological scores （P<0.05）， increased Ly6C^hi and Ly6C^lo monocytes/macrophages （P<0.05）， and up-regulated mRNA levels of TLR4， TNF-α， IL-1β， and IL-6 （P<0.05） and protein levels of TLR4， phosphorylated extracellular signal-regulated protein kinase 1/2 （p-ERK1/2）， and phosphorylated p38 MAPK （p-p38 MAPK） （P<0.05）. Zingiberis Rhizoma intervention reversed these changes and reduced Ly6C^hi monocytes/macrophages （P<0.01）. In vitro experiments： compared with the control， LPS increased the proportion and number of Ly6C^hi monocytes/macrophages and mRNA levels of TLR4， TNF-α， IL-1β， and IL-6 （P<0.01） and enhanced the expression of TLR4， p-ERK1/2， and p-p38 MAPK （P<0.05）. Zingiberis Rhizoma reduced Ly6C^hi monocytes/macrophages （P<0.05）， down-regulated the mRNA levels of inflammatory cytokines （P<0.05）， and suppressed the TLR4/MAPK pathway （P<0.05）. ConclusionZingiberis Rhizoma alleviates IBD by suppressing the TLR4/ERK/p38 MAPK signaling pathway and reducing inflammatory cytokine levels in Ly6C^hi monocytes/macrophages.

ObjectiveTo clarify the repair effect of Mume Fructus on the intestinal mucosal epithelial barrier in the mouse model of inflammatory bowel disease （IBD） and explore the repair mechanism. MethodsThirty-six male C57BL/6 mice were randomly assigned into six groups： normal， model， low-， medium-， and high-dose （200， 400， and 800 mg·kg^-1） Mume Fructus， and sulfasalazine （300 mg·kg^-1）. Except the normal group， the rest groups had free access to 2% dextran sulfate sodium （DSS） solution for seven days to establish the IBD model， followed by a seven-day drug intervention. The body weight change and disease activity index （DAI） were recorded. After the last administration， spleen and colon tissue samples were collected to analyze the differences in colon length and spleen index. Hematoxylin-eosin staining was used to observe the morphology of the colon tissue. The level of diamine oxidase （DAO） in the serum was measured by the DAO assay kit. Immunohistochemistry was employed to determine the expression of tight junction proteins such as Claudin-1， Occludin， and zonula occludens-1 （ZO-1） in the colon tissue. Real-time PCR was performed to measure the mRNA levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the colon tissue. Finally， Western blot was employed to determine the protein levels of mitogen-activated protein kinase kinase （MEK）， extracellular signal-regulated kinase （ERK）， phosphorylated （p）-MEK， and phosphorylated ERK in the colon tissue. ResultsCompared with the normal group， the model group exhibited decreases in body weight and colon length （P<0.01）， increases in DAI， spleen index， and serum DAO level （P<0.01）， damaged colonic epithelium and goblet cells， and obvious infiltration of inflammatory cells. In addition， the model group exhibited higher positive expression of Claudin-1， Occludin， and ZO-1 （P<0.01）， higher mRNA levels of TNF-α and IL-1β （P<0.01）， and higher protein levels of p-MEK and p-ERK （P<0.05， P<0.01） than the normal group. However， sulfasalazine and three doses of Mume Fructus markedly decreased the body weight and DAI （P<0.05）， recovered the colon length and spleen index， alleviated colon tissue damage， lowered the level of DAO in the serum （P<0.01）， and down-regulated the mRNA levels of TNF-α and IL-1β （P<0.01） and the protein levels of p-MEK and p-ERK （P<0.05）. Sulfasalazine and low- and medium-dose Mume Fructus increased the positive expression of Occludin， Claudin-1， and ZO-1 （P<0.05， P<0.01）. Furthermore， high-dose Mume Fructus elevated the protein expression of Occludin （P<0.05）. ConclusionMume Fructus can restore the expression of intestinal epithelial tight junction proteins by inhibiting the phosphorylation of proteins in the MEK/ERK signaling pathway and down-regulating the levels of TNF-α and IL-1β， thus repairing the intestinal mucosal barrier in the mouse model of IBD.

ObjectiveTo investigate the modulating effect of modified Wumeiwan （MWMW） on the ulcerative colitis （UC）-associated intestinal helper T cell 17 （Th17）/regulatory T cell （Treg） balance and intestinal flora by using a human flora-associated model of UC patients with dampness-heat obstruction syndrome， thus providing a new idea for the UC-related research and therapeutic strategies. MethodsThe 24 male C57BL/6J mice were randomized into normal control， model， and MWMW groups （n=8）. Model and MWMW groups were first treated with an antibiotic cocktail （vancomycin， 0.1 g·kg^-1； neomycin sulfate， 0.2 g·kg^-1； ampicillin， 0.2 g·kg^-1； metronidazole， 0.2 g·kg^-1） for 21 days. At the end of antibiotic treatment， the gavage of fecal microbiota suspension from UC patients with dampness-heat obstruction syndrome was started at a dose of 0.2 mL·d^-1 for 19 consecutive days， by which a human flora-associated model of UC was obtained. The MWMW group was administrated daily with MWMW liquid （12.5 g·kg^-1）， while the normal control and model groups were administrated by gavage with an equal amount of sterile water for 7 consecutive days. The symptoms of dampness-heat obstruction were observed. The colon length and spleen index were measured and calculated， and the proportions of Th17 and Treg cells were detected by flow assay. The intestinal flora was analyzed by 16S rRNA high-throughput sequencing. ResultsCompared with the normal control group， the model group showed shortened colon （P<0.05） and increased spleen index （P<0.01）. Compared with the model group， the MWMW group showed prolonged colon （P<0.01） and decreased spleen index （P<0.05）. After the intervention of MWMW， the Th17 proportion and Th17/Treg ratio in the colon decreased （P<0.01）， and the proportion of Treg cells increased （P<0.05）. The number of species and alpha and beta diversity of intestinal flora in mice were regulated by MWMW （P<0.05）. In terms of intestinal flora composition， MWMW increased the relative abundance of several phyla （Firmicutes， Proteobacteria， Fusobacteriota， Actinobacteriota， and Gemmatimonadota）， the genus Bacteroides， and two species （Bacteroides thetaiotaomicron and B. fragilis） in model mice. Moreover， Spearman's correlation analysis showed that the relative abundance of B. thetaiotaomicron and B. fragilis were negatively correlated with the Th17 level （P<0.05）. In addition， the above changes in intestinal flora caused the changes in microbial genes involved in 14 pathways， such as glycolysis， amino acid degradation， inorganic nutrient metabolism， biosynthesis of pyrimidine deoxyribonucleotides， antibiotic resistance， and degradation of polysaccharides. ConclusionsThe human flora-associated model successfully simulated the changes （marked by a decrease in the abundance of Bacteroides） of intestinal flora in UC patients with dampness-heat obstruction syndrome. MWMW can enrich the abundance of beneficial bacteria such as B. thetaiotaomicron and B. fragilis and promote the synergistic intestinal immune modulation with the metabolic functions centered on glycolysis， amino acid metabolism， and nucleotide synthesis through bacterial polysaccharide utilization sites to reduce the Th17/Treg ratio， thereby exerting a protective effect on UC.

Obejective To explore whether it is possible to detect the 123I-prostate-specific membrane antigen(PSMA)radiation value of the puncture tissue during prostate biopsy to achieve real-time,rapid,and accurate identification of benign and malignant prostate tissues,so as to improve the current clinical biopsy strategy and achieve accurate diagnosis of prostate cancer during operation with fewer puncture needles.Method In this prospective,diagnostic trial,we included 29 patients with suspected prostate cancer.All patients underwent transperineal biopsy guided by ultrasound within 24 hours after injection of 123I-PSMA,a total of 435 punctures were performed.The radiation value of punctured tissue was measured in real-time with a gamma counter.Pearson test is used to correlate radiation value with histopathology.Result The median radiation value of prostate cancer tissue(1 906.50 cpm)was significantly higher than that of benign prostate tissue(415.00 cpm).The optimal cut-off value for distinguishing benign and malignant prostate tissues was 828.50 cpm.The median radiation value of clinically significant prostate cancer tissue(2 652.50 cpm)was significantly higher than that of clinically insignificant prostate cancer(1 386.00 cpm).The optimal cut-off value for distinguishing clinically significant and clinically insignificant prostate cancer tissues was 1 767.00 cpm.In additional,there was a significant positive correlation between the radiation value of puncture tissue and ISUP pathological grade(r=0.834).Conclusion It is preliminarily confirmed that detection of 123I-PSMA radiation value of prostate puncture tissue can realize real-time,rapid and accurate identification of benign and malignant prostate tissues during operation.

Objective:To compare the clinical efficacy of endoscopic posterior transforaminal lumbar interbody fusion (Endo-PTLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of single-segment lumbar degenerative diseases.Methods:A retrospective analysis was conducted on the clinical data of 56 patients with single-segment lumbar degenerative diseases treated at Xiuzhou District People's Hospital between September 2020 and March 2023. Patients were divided into two groups based on the surgical approach: the Endo-PTLIF group (24 cases, 11 males and 13 females; mean age: 56.5±8.4 years, range: 43-72 years) and the MIS-TLIF group (32 cases, 10 males and 22 females; mean age: 54.5±10.4 years, range: 37-73 years). Perioperative parameters, visual analog scale (VAS) scores for pain, Oswestry disability index (ODI), lumbar lordosis (LL), disc height (DH), and dural sac cross-sectional area (DSCA) were compared between the two groups.Results:No significant differences were observed between the two groups in baseline characteristics, preoperative VAS, ODI, LL, DH, or DSCA ( P>0.05). However, the operative time in the Endo-PTLIF group (173.9±12.3 minutes) was significantly longer than in the MIS-TLIF group (136.5±19.5 minutes, P<0.05). Similarly, the Endo-PTLIF group required more fluoroscopy exposures (15.9±1.8) than the MIS-TLIF group (13.0±1.6, P<0.05). In contrast, intraoperative blood loss in the Endo-PTLIF group (68.9± 12.9 ml) was significantly lower than in the MIS-TLIF group (126.7±35.4 ml, P<0.05). Additionally, the Endo-PTLIF group had a shorter hospital stay [7.00 (6.25, 7.75) days] compared to the MIS-TLIF group [10.00 (9.25, 11.00) days, P<0.05]. At one week and one month postoperatively, the Endo-PTLIF group had significantly lower back pain VAS scores [2.00 (2.00, 3.00) and 2.00 (2.00, 2.00), respectively] and a lower ODI (25.83%±3.83%) compared to the MIS-TLIF group [3.00 (2.25, 4.00), 2.50 (2.00, 3.00), and 30.09%±4.02%, respectively; P<0.05]. Beyond one month postoperatively, there were no significant differences in leg pain VAS scores between the groups, and back pain VAS and ODI showed no significant differences after six months ( P>0.05). At the final follow-up, the excellent and good rates, according to MacNab criteria, were 95.8% in the Endo-PTLIF group and 93.8% in the MIS-TLIF group, with no significant difference ( P>0.05). At 12 months postoperatively, both groups showed significant improvements in LL, DH, and DSCA compared to preoperative values ( P<0.05), but there were no significant differences between the two groups ( P>0.05). The fusion rates were 96% in the Endo-PTLIF group and 94% in the MIS-TLIF group, with no significant difference ( P>0.05). Complications included one case of dural tear in the Endo-PTLIF group, and one case of dural tear and one case of incision infection in the MIS-TLIF group. Conclusion:Endo-PTLIF achieves comparable clinical efficacy to MIS-TLIF in the treatment of single-segment lumbar degenerative diseases, with the added advantages of reduced intraoperative blood loss and faster postoperative recovery.

Objective:To compare the clinical efficacy of endoscopic posterior transforaminal lumbar interbody fusion (Endo-PTLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of single-segment lumbar degenerative diseases.Methods:A retrospective analysis was conducted on the clinical data of 56 patients with single-segment lumbar degenerative diseases treated at Xiuzhou District People's Hospital between September 2020 and March 2023. Patients were divided into two groups based on the surgical approach: the Endo-PTLIF group (24 cases, 11 males and 13 females; mean age: 56.5±8.4 years, range: 43-72 years) and the MIS-TLIF group (32 cases, 10 males and 22 females; mean age: 54.5±10.4 years, range: 37-73 years). Perioperative parameters, visual analog scale (VAS) scores for pain, Oswestry disability index (ODI), lumbar lordosis (LL), disc height (DH), and dural sac cross-sectional area (DSCA) were compared between the two groups.Results:No significant differences were observed between the two groups in baseline characteristics, preoperative VAS, ODI, LL, DH, or DSCA ( P>0.05). However, the operative time in the Endo-PTLIF group (173.9±12.3 minutes) was significantly longer than in the MIS-TLIF group (136.5±19.5 minutes, P<0.05). Similarly, the Endo-PTLIF group required more fluoroscopy exposures (15.9±1.8) than the MIS-TLIF group (13.0±1.6, P<0.05). In contrast, intraoperative blood loss in the Endo-PTLIF group (68.9± 12.9 ml) was significantly lower than in the MIS-TLIF group (126.7±35.4 ml, P<0.05). Additionally, the Endo-PTLIF group had a shorter hospital stay [7.00 (6.25, 7.75) days] compared to the MIS-TLIF group [10.00 (9.25, 11.00) days, P<0.05]. At one week and one month postoperatively, the Endo-PTLIF group had significantly lower back pain VAS scores [2.00 (2.00, 3.00) and 2.00 (2.00, 2.00), respectively] and a lower ODI (25.83%±3.83%) compared to the MIS-TLIF group [3.00 (2.25, 4.00), 2.50 (2.00, 3.00), and 30.09%±4.02%, respectively; P<0.05]. Beyond one month postoperatively, there were no significant differences in leg pain VAS scores between the groups, and back pain VAS and ODI showed no significant differences after six months ( P>0.05). At the final follow-up, the excellent and good rates, according to MacNab criteria, were 95.8% in the Endo-PTLIF group and 93.8% in the MIS-TLIF group, with no significant difference ( P>0.05). At 12 months postoperatively, both groups showed significant improvements in LL, DH, and DSCA compared to preoperative values ( P<0.05), but there were no significant differences between the two groups ( P>0.05). The fusion rates were 96% in the Endo-PTLIF group and 94% in the MIS-TLIF group, with no significant difference ( P>0.05). Complications included one case of dural tear in the Endo-PTLIF group, and one case of dural tear and one case of incision infection in the MIS-TLIF group. Conclusion:Endo-PTLIF achieves comparable clinical efficacy to MIS-TLIF in the treatment of single-segment lumbar degenerative diseases, with the added advantages of reduced intraoperative blood loss and faster postoperative recovery.

Obejective To explore whether it is possible to detect the 123I-prostate-specific membrane antigen(PSMA)radiation value of the puncture tissue during prostate biopsy to achieve real-time,rapid,and accurate identification of benign and malignant prostate tissues,so as to improve the current clinical biopsy strategy and achieve accurate diagnosis of prostate cancer during operation with fewer puncture needles.Method In this prospective,diagnostic trial,we included 29 patients with suspected prostate cancer.All patients underwent transperineal biopsy guided by ultrasound within 24 hours after injection of 123I-PSMA,a total of 435 punctures were performed.The radiation value of punctured tissue was measured in real-time with a gamma counter.Pearson test is used to correlate radiation value with histopathology.Result The median radiation value of prostate cancer tissue(1 906.50 cpm)was significantly higher than that of benign prostate tissue(415.00 cpm).The optimal cut-off value for distinguishing benign and malignant prostate tissues was 828.50 cpm.The median radiation value of clinically significant prostate cancer tissue(2 652.50 cpm)was significantly higher than that of clinically insignificant prostate cancer(1 386.00 cpm).The optimal cut-off value for distinguishing clinically significant and clinically insignificant prostate cancer tissues was 1 767.00 cpm.In additional,there was a significant positive correlation between the radiation value of puncture tissue and ISUP pathological grade(r=0.834).Conclusion It is preliminarily confirmed that detection of 123I-PSMA radiation value of prostate puncture tissue can realize real-time,rapid and accurate identification of benign and malignant prostate tissues during operation.

Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensi-tivity in HCC therapy.Although several synthesized GST inhibitors have been developed,the side effects and narrow spectrum for anticancer seriously limit their clinical application.Considering the abundance of natural compounds with anticancer activity,this study developed a rapid fluorescence technique to screen"green"natural GST inhibitors with high specificity.The fluorescence assay demonstrated that schisanlactone B(hereafter abbreviated as C1)isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo.Importantly,C1 can selectively kill HCC cells from normal liver cells,effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression.Considering the high GST levels in HCC patients,this compound demon-strated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

Objective To compare the clinical efficacy and imaging results of uniportal interlaminar endoscopy(UIE)and unilateral biportal endoscopy(UBE)for the treatment of lumbar disc herniation.Methods The clinical information for 50 patients diagnosed with lumbar disc herniation was collected,and treated by UIE endoscopic surgery and UBE endoscopic surgery in the The First People's Hospital of Hefei city from March 2021 to October 2022 were retrospectively analyzed.The patients were divided into two groups,UIE group and the UBE group.Perioperative indexes including incision length,operation time,intraoperative blood loss,and surgical complications,clinical efficacy indexes including VAS scores of low back pain and leg pain before surgery,3 days after surgery,3 months after surgery,6 months after surgery,and 12 months after surgery,ODI scores of dysfunc-tion index,and imaging results including spinal canal area,vertebral space height,before surgery and 1 year after surgery were recorded and compared between the two groups.Results Both groups completed the procedure and were followed up for 12～18 months,with an average of 15 months.1 case was dural injury,no nerve root injury,and no nerve root symptoms during the follow-up.The symptoms of lumbar and leg pain were all relieved in both groups after the procedure.The UBE groups hawed larger surgical incisions,more intraoperative blood loss,and shorter operative time compared to the UIE group(P＜0.05,respectively).Both groups had significant develop-ments in the VAS scores,ODI scores of back,and leg pain at 3 days,3 months,6 months,and 12 months after the operation(all P＜0.05).The UIE group showed significant developments in the VAS scores and ODI scores of back and leg pain at 3 days and 3 months after the operation,as compared to the UBE group(P＜0.05).The imaging analysis did not showed significant changes in the height of intervertebral space and the angle of lumbar lordosis,but a significantly larger increase in the dural sac area in both groups one year after the procedure,and the UBE group had even a larger increase than the UIE group(P＜0.05).Conclusion Both UIE and UBE have good clinical efficacy and imaging results in the treatment of lumbar disc herniation via interlaminal approach.However,the UIE group is superior to the UBE group in terms of the operation time,intraoperative blood loss,postoperative VAS score of low back pain as well as the decompression effectiveness.