AIM: To investigate the impacts of periocular injection of triamcinolone acetonide on healing effect and inflammatory factor in patients with acute iridocyclitis.METHODS:Totally 90 patients(90 eyes)with acute iridocyclitis, admitted to our hospital between September 2018 and September 2023, were grouped via random number table, including a triamcinolone acetonide group and a control group, each comprising 45 patients(45 eyes). The control group underwent conventional treatment, whereas the triamcinolone acetonide group adopted triamcinolone acetonide through periocular injection. The healing effect, levels of inflammatory cytokines, anterior chamber inflammatory cell scores, keratic precipitates(KP)scores, best-corrected visual acuity(BCVA), untoward reactions, and relapse rates of the two groups of patients were compared.RESULTS:The triamcinolone acetonide group had significantly higher overall efficacy rate than the control group(P<0.05). The levels of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interferon-γ(IFN-γ)decreased in both groups at 30 d after treatment, and the levels in the triamcinolone acetonide group were lower(all P<0.05). After treatment for 30 d, the scores of anterior chamber inflammatory cells and KP in both groups decreased, and the scores in the triamcinolone acetonide group were lower than those in the control group(all P<0.05); the BCVA of both groups improved, and the triamcinolone acetonide group had a better BCVA(all P<0.05). There was no statistically significant difference in untoward reactions between the two groups(P=1.000). The relapse rate of the triamcinolone acetonide group was lower than that of the control group(P=0.030).CONCLUSION: Periocular injection of triamcinolone acetonide has obvious healing effects on patients with acute iridocyclitis, and it can alleviate the inflammatory state of patients and reduce the relapse rate of inflammation.

BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*

Objective To explore macrophage subpopulations in ischemic stroke (IS) by using single-cell RNA sequencing (scRNA-seq) data analysis and High-Dimensional Weighted Gene Co-Expression Network Analysis (hdWGCNA). Methods Based on single-cell sequencing data, transcriptomic information for different cell types was obtained, and macrophages were selected for subpopulation identification. hdWGCNA, cell-cell communication, and pseudotime trajectory analysis were used to explore the characteristics of macrophage subpopulations following IS. Key genes related to IS were identified using microarray data and validated for diagnostic potential through Receiver Operating Characteristic (ROC) analysis. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential functions of these genes. Results The scRNA-seq data analysis revealed significant changes in macrophage subpopulation composition after IS. A specific macrophage subpopulation enriched in the stroke group was identified and designated as MCAO-specific macrophages (MSM). Pseudotime trajectory analysis indicated that MSM cells were in an intermediate stage of macrophage differentiation. Cell-cell communication analysis uncovered complex interactions between MSM cells and other cells, with the CCL6-CCR1 signaling axis potentially playing a crucial role in neuroinflammation. Two gene modules associated with MSM were identified via hdWGCNA, significantly enriched in pathways related to NOD-like receptors and antigen processing. By integrating differentially expressed MSM genes with conventional transcriptomic data, three IS-related hub genes were identified: Arg1, CLEC4D, and CLEC4E. Conclusion This study reveals the characteristics and functions of macrophage subpopulations following IS and identifies three hub genes with potential diagnostic value, providing novel insights into the pathological mechanisms of IS.
Macrophages/metabolism* ; Computational Biology/methods* ; Single-Cell Analysis/methods* ; Transcriptome ; Ischemic Stroke/metabolism* ; Animals ; Gene Regulatory Networks ; Gene Expression Profiling ; Humans ; Male

Objective:To explore the mechanism of Honghua Xiaoyao Tablets in the treatment of premature ovarian failure (POF) using network pharmacology and molecular docking technology; To conduct further experimental verification.Methods:The active components and related targets of Honghua Xiaoyao Tablets were obtained using TCMSP and PubChem databases, and the related targets of POF were obtained by using GeneCards database. The Venn online tool was used to screen the intersection genes, and the STRING database was used to construct the PPI network. Then, GO function enrichment analysis and KEGG pathway enrichment analysis were performed on the intersecting genes through the Metescape database, and Cytoscape 3.7.1 software was used to construct the "active component-target" network and "Chinese materia medica-active component-target-key pathway-disease" network. Finally, molecular docking verification was carried out. Mice were divided into blank group, model group, and Honghua Xiaoyao Tablets group using a random number table method, with 8 mice in each group. Except for the blank group, mice in each group were treated with zona pellucida polypeptide 3 (ZP3) and Freund's Complete Adjuvant (FCA) to establish a mouse model of immune POF. Mice in the Honghua Xiaoyao Tablets group received Honghua Xiaoyao Tablets solution 0.56 g/kg for gavage, and the blank control group and the model group received saline for gavage for consecutive 4 weeks. The histopathological changes of the mouse ovary were observed by HE staining. Immunohistochemical staining was used to observe the expression of ESR1, and Western blot was used to detect the expressions of Akt and p-Akt.Results:A total of 80 intersection targets between Honghua Xiaoyao Tablets and POF were obtained, and the PPI network contained 44 core targets. The top 5 compounds in the topological analysis were formononetin, quercetin, Betulinic acid, Hydroxysafflor Yellow A and Baicalin, and the top 5 targets were PPARG, ESR1, AR, AKT1 and IL6. The molecular function of core genes was mainly receptor ligand activity, and its biological process mainly involved the positive regulation of cell migration. The cellular components mainly included membrane rafts, which were involved in signaling pathways such as cancer signaling pathway, proteoglycans in cancer, PI3K-Akt signaling pathway, and HIF-1 signaling pathway. "Chinese materia medica-component-target-pathway-disease" network showed that 8 kinds of Chinese materia medica in the Honghua Xiaoyao Tablets had important core components, among which Glycyrrhizae Radix et Rhizoma and Carthami Flos involved the most important core components. Molecular docking results showed that the active components had a good affinity with the core target. The experimental verification confirmed that Honghua Xiaoyao Tablets promoted follicular development, increased the expression of ESR1 in ovarian tissues and up-regulated the expression level of the key factor of Akt phosphorylation in the PI3K-Akt signaling pathway.Conclusions:The various active components of Honghua Xiaoyao Tablets may act on PPARG, ESR1 and other targets through multiple signaling pathways such as PI3K-Akt and HIF-1 to treat POF. The potential active components are mainly formononetin, quercetin, etc.

Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), is a common hepatic manifestation of metabolic syndrome. However, there are no effective therapy to treat this devastating disease. Accumulating evidence suggests that the generation of elastin-derived peptides (EDPs) and the inhibition of adiponectin receptors (AdipoR)1/2 plays essential roles in hepatic lipid metabolism and liver fibrosis. We recently reported that the AdipoR1/2 dual agonist JT003 significantly degraded the extracellular matrix (ECM) and ameliorated liver fibrosis. However, the degradation of the ECM lead to the generation of EDPs, which could further alter liver homeostasis negatively. Thus, in this study, we successfully combined AdipoR1/2 agonist JT003 with V14, which acted as an inhibitor of EDPs-EBP interaction to overcome the defect of ECM degradation. We found that combination of JT003 and V14 possessed excellent synergistic benefits on ameliorating NASH and liver fibrosis than either alone since they compensate the shortage of each other. These effects are induced by the enhancement of the mitochondrial antioxidant capacity, mitophagy, and mitochondrial biogenesis via AMPK pathway. Furthermore, specific suppression of AMPK could block the effects of the combination of JT003 and V14 on reduced oxidative stress, increased mitophagy and mitochondrial biogenesis. These positive results suggested that this administration of combination of AdipoR1/2 dual agonist and inhibitor of EDPs-EBP interaction can be recommended alternatively for an effective and promising therapeutic strategy for the treatment of NAFLD and NASH related fibrosis.

Objective:To analyze the pathogens distribution, drug resistance and risk factors of bacterial infection in patients undergoing liver transplantation for liver failure.Methods:The retrospective case-control study was conducted. The clinical data of 88 patients with liver failure who underwent liver transplantation in The First Affiliated Hospital of Xi′an Jiaotong University from July 2020 to June 2023 were collected. There were 57 males and 31 females, aged (44±9)years. Observation indicators:(1) incidence and pathogens distribution of bacterial infection in patients undergoing liver transplantation for liver failure; (2) drug resistance of bacteria; (3) risk factors of bacterial infection in patients undergoing liver transplantation for liver failure. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers and percentages. Univariate analysis was conducted using the chi-square test or Fisher exact probability. Multivariate analysis was conducted using the Logistic regression model. Results:(1) Incidence and pathogens distribution of bacterial infection in patients undergoing liver transplantation for liver failure. Of 88 patients, 40 cases had bacterial infection after liver transplantation, with the incidence as 45.45% and occurrence time as postoperative 18(range, 1-57)days. Of the 40 cases with bacterial infection after liver transplantation, 9 cases had single strain infection and 31 cases had mixed bacterial infection. A total of 135 strains of different pathogenic bacteria were isolated from 40 patients, 106 of which were Gram-negative bacteria, 29 were Gram-positive bacteria. Of the Gram-negative bacteria, the top 4 pathogenic bacteria were 37 strains of Acinetobacter baumannii, 35 strains of Klebsiella pneumoniae, 11 strains of Pseudomonas aeruginosa, 9 strains of Stenotrophomonas maltophilia. Of the Gram-positive bacteria, there were 22 strains of Enterococcus faecium, 3 strains of Staphylococcus aureus, 3 strains of Staphylococcus epidermidis, 1 strain of Staphylococcus haemolyticus. Of the 135 strains of pathogenic bacteria, 64 strains were isolated from respiratory tract, 26 strains were from abdomen, 23 strains were from biliary tract, 16 strains were from blood, 6 strains were from other sites. (2) Drug resistance of bacteria. Of the Gram-negative bacteria, Acinetobacter baumannii had a resistance rate of lower than 30.0% to colistin, tigacyclinei, minocycline, a resistance rate of 30.0%-50.0% to amikacin and tobramycin, a resistance rate of over 70.0% to cefotetan, ceftazidime, cefepime, cefoperazone/sulbactam, piperacillin/tazobactam, meropenem, imipenem, ciprofloxacin, cotrimoxazole, levofloxacin. Klebsiella pneumoniae showed a resistance rate of lower than 30.0% to ceftazidime/avibactam, colistin, tigacyclinei and a resistance rate of more than 70.0% to other tested antibiotics. Pseudomonas aeruginosa showed a resistance rate of more than 50.0% to meropenem, imipenem, levofloxacin and a resistance rate of lower than 50.0% to other tested antibiotics. Stenotrophomonas maltophilia showed a resistance rate of lower than 30.0% to cotrimoxazole, levofloxacin, minocycline. Klebsiella oxytoca showed a resistance rate of more than 50.0% to piperacillin/tazobactam, cefoperazone/sulbactam and a resistance rate of lower than 50.0% to other tested antibiotics. The resistance rate of Escherichia coli to amikacin, tobramycin, ceftazidime/avibactam, colistin, and tigecycline was less than 30.0%, and the resistance rate to other tested antibiotics was more than 50.0%. Of the Gram-positive bacteria, Staphylococcus aureus showed a resistance rate of 0 to tigacyclinei, vancomycin, teicoplanin, linezolid, a resistance rate of lower than 50.0% to gentamicin and ciprofloxacin, and a resistance rate of more than 50.0% to erythromycin, penicillin G, ampicillin, tetracycline, levofloxacin. Staphylococcus showed a resistance rate of more than 50.0% to erythromycin, penicillin G, oxacillin, and a resistance rate of 0 to other tested antibiotics. (3) Risk factors of bacterial infection in patients undergoing liver transplantation for liver failure. Results of multivariate analysis showed that preoperative model for end-stage liver disease score ≥30 was an independent risk factor for bacterial infection in patients undergoing liver transplantation for liver failure ( odds ratio=6.440, 95% confidence interval as 2.155-19.248, P<0.05). Conclusions:The incidence of bacterial infection in patients undergoing liver transplantation for liver failure is high, with the most common sites of respiratory tract and abdomen. The pathogenic bacteria are mainly Gram-negative bacteria, which show an extensive and high drug resistance. Preoperative model for end-stage liver disease score ≥30 was an independent risk factor for bacterial infection in patients undergoing liver transplantation for liver failure.

Objective:To evaluate the effect of exosomes derived from bone mesenchymal stem cells (BMSCs-EXO) on the postoperative cognitive function and silent infomation regulator 1 (SIRT1)/ nuclear factor kappa B (NF-κB) signaling pathway in aged mice.Methods:BMSCs-EXO were isolated by differential centrifugation method and then identified. Twenty healthy male C57BL/6 aged mice, aged 18 months, weighing 35-40 g, were divided into 4 groups ( n=5 each) using a random number table method: sham operation group (Sham group), operation group (O group), BMSCs-EXO group and EX527 (SIRT1 inhibitor)group. The abdomen regions were shaved for sterilization without exploratory laparotomy in Sham group. Exploratory laparotomy was performed in O group. BMSCs-EXO 50 μg was injected through the tail vein at 1 h before surgery in BMSCs-EXO group. EX527 5 mg/kg was intraperitoneally injected daily at 1-3 days before surgery, and BMSCs-EXO 50 μg was injected through the tail vein at 1 h before surgery in EX527 group. Morris water maze test was used to evaluate the learning and memory ability for 5 consecutive days staring from the 1st day after surgery. Mice were sacrificed at 1 h after the end of Morris water maze test on day 5 after surgery, and the hippocampal tissues were collected for observation of the pathological changes of hippocampal CA1 region and for determination of the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1β mRNA (quantitative real-time polymerase chain reaction) and SIRT1 and NF-κB p65 (by Western blot). Results:Compared with Sham group, the escape latency was significantly prolonged, the times of original platform crossing were decreased, the swimming time spent in the original platform quadrant was shortened, the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1β mRNA was up-regulated, the SIRT1 expression was down-regulated, the NF-κB p65 expression was up-regulated ( P<0.05), and the pathological changes of hippocampal tissues in CA1 region were found in O group. Compared with O group, the escape latency was significantly shortened, the times of original platform crossing were increased, the swimming time spent in the original platform quadrant was prolonged, the expression of TNF-α, IL-6 and IL-1β mRNA was down-regulated, the expression of SIRT1 was up-regulated, the expression of NF-κB p65 was down-regulated ( P<0.05), and the pathological changes of hippocampal tissues in CA1 region were significantly attenuated in BMSCs-EXO group ( P<0.05). Compared with BMSCs-EXO group, the escape latency was significantly prolonged, the times of original platform crossing were decreased, the swimming time spent in the original platform quadrant was shortened, the expression of TNF-α, IL-6 and IL-1β mRNA was up-regulated, the SIRT1 expression was down-regulated, the NF-κB p65 expression was up-regulated ( P<0.05), and the pathological changes of hippocampal tissues in CA1 region were accentuated in EX527 group. Conclusions:BMSCs-EXO can improve the postoperative cognitive function in aged mice, and the mechanism may be associated with the activation of SIRT1/NF-κB signaling pathway.

OBJECTIVE To identify the chemical components of Changtong oral liquid （CTOL），and to provide reference for the basic research and secondary development of its pharmacological substances. METHODS UHPLC-Orbitrap HRMS technique was adopted. CTOL sample was separated on a Hypersil Gold column with mobile phase consisted of 0.1% formic acid （containing 5 mmol/L ammonium formate）-acetonitrile （gradient elution）. The eluent was detected in positive and negative ion modes using an electrospray ionization source. The data was processed by Xcalibur 4.3 and Compound Discoverer 3.3 software. The primary and secondary mass spectra data of each compound were collected. The unknown compounds were identified according to the mass spectrometry library of the instrument and the network databases mzCloud，mzVault，etc. Through matching with the pharmacology database and analysis platform of the traditional Chinese medicine system，the chemical components could be attributed to the traditional Chinese medicine. RESULTS Fifty-three chemical components were identified and analyzed from CTOL，such as 24 flavonoids，8 quinones，5 phenylpropanoids，4 sugars and glycosides，5 organic acids，3 amino acids，1 alkaloid，1 phenolic and 2 other compounds. Among them，12 components were derived from Salvia miltiorrhiza，9 from Citrus aurantium，7 from Rheum palmatum，4 from Angelica sinensis，1 from Magnolia officinalis，16 from Glycyrrhiza uralensis，and 4 from many kinds of medicinal materials. CONCLUSIONS CTOL mainly contains flavonoids，quinones and phenylpropanoid compounds，and its chemical components mainly come from G. uralensis，S. miltiorrhiza and C. aurantium.

Recently, the number of severe obesity in China has now ranked first in the world. The amount of metabolic and bariatric surgery in China is increasing year by year, and has made rapid development. As more and more new hospitals, surgical teams, and physicians join the field of metabolic and bariatric surgery, suboptimal operations and managements will inevitably accompany, causing problems and hidden dangers related to bariatric surgery. To a certain extent, this is in line with the law of development, but it does not mean that we can leave it alone and let it develop. In order to ensure the sustainable, healthy and orderly development of metabolic and bariatric surgery in China in the future, the standardized construction and quality improvement have become an urgent task. This paper reviews the current status of standardized construction of metabolic and bariatric surgery at home and abroad, the necessities and paths to quality improvement of standardized construction of metabolic and bariatric surgery in China, in order to put forward some thoughts and arouse extensive discussions for the development of the subject.

Recently, the number of severe obesity in China has now ranked first in the world. The amount of metabolic and bariatric surgery in China is increasing year by year, and has made rapid development. As more and more new hospitals, surgical teams, and physicians join the field of metabolic and bariatric surgery, suboptimal operations and managements will inevitably accompany, causing problems and hidden dangers related to bariatric surgery. To a certain extent, this is in line with the law of development, but it does not mean that we can leave it alone and let it develop. In order to ensure the sustainable, healthy and orderly development of metabolic and bariatric surgery in China in the future, the standardized construction and quality improvement have become an urgent task. This paper reviews the current status of standardized construction of metabolic and bariatric surgery at home and abroad, the necessities and paths to quality improvement of standardized construction of metabolic and bariatric surgery in China, in order to put forward some thoughts and arouse extensive discussions for the development of the subject.