ObjectiveTo investigate the effect and mechanism of Polygonatum neutral polysaccharides from sibiricum （PSP-NP） on colon injury in mice with chronic obstructive pulmonary disease （COPD）. MethodsMale C57BL/6J mice were randomly divided into a control group， a COPD model group， and a PSP-NP group. The COPD model was established using smoke exposure combined with intranasal LPS administration. The PSP-NP group was simultaneously treated daily with 200 mg/kg of PSP-NP via intragastric gavage， while the other groups received an equal volume of saline. HE staining was used to observe the pathological changes in the colon. ELISA was employed to detect the levels of LPS in serum and the expressions of ZO-1， Occludin， IL-6， and TNF-α in colon tissue. UPLC-MS was used to detect the types and contents of bile acids in colonic content， and to screen for differential bile acids. Differential microbial flora were identified using 16S rRNA gene sequencing， and correlation analysis was conducted with differential bile acids. PSP-NP was combined with the differential bile acids cholic acid （CA）， and deoxycholic acid （DCA） in vitro to analyze the binding capacity of PSP-NP for CA and DCA. PSP-NP was applied to NCM460 normal colonic epithelial cells cultured in CA and DCA. Cell migration ability was assessed using the scratch assay， and the mRNA expression levels of inflammatory cytokines TNF-α， IL-6， and NF-κB were measured by RT-qPCR. ResultsPSP-NP effectively improved colonic damage in COPD model mice， enhanced mechanical barrier function， alleviated inflammatory response， and regulated abnormal changes in colonic flora and bile acid metabolism. Correlation analysis further revealed that PSP-NP regulated colonic bile acid metabolism and reduced the redundancy of secondary bile acids by increasing the relative abundance of Bacteroidota， Verrucomicrobiota， Bacteroides， and Akkermansia， while decreasing the relative abundance of Lactobacillus and Bifidobacterium. Notably， in vitro binding assays demonstrated that PSP-NP bound to differential bile acids DCA and CA， with the strongest binding capacity for DCA at 58.2%. In cellular functional studies， DCA inhibited the migration ability of colonic epithelial cells NCM460 and significantly increased the relative mRNA expression levels of inflammatory factors TNF-α， IL-6， and NF-κB. Importantly， co-treatment with PSP-NP significantly ameliorated the impact of DCA on NCM460 cells. ConclusionsPSP-NP may significantly improve colonic damage in COPD model mice. The mechanism may involve the regulation of colonic bile acid metabolism and bile acid profiles through both microbial modulation and direct binding， thereby reducing the damage caused by secondary bile acids such as DCA to colonic epithelial cells.

Flavoprotein monooxygenases(FPMOs) and cytochrome P450(CYP450) oxygenases are pivotal monooxygenases in nature, catalyzing crucial redox reactions in diverse biological processes and contributing to the synthesis of highly complex natural products. While CYP450 enzymes have been extensively reported and studied, numerous FPMOs have also been discovered in past research endeavors, yet their classification, catalytic reactions, and catalytic mechanisms remain to be systematically analyzed. This paper comprehensively reviews the latest advancements in FPMOs research, initiating with a classification based on sequence similarities and distinct structural features. It delves into the catalytic characteristics of three subfamilies(FMO, BVMO, and NMO) within Class B FPMOs of plants, which are integral to biosynthetic pathways of natural products. Class B FPMOs encompass two canonical Rossmann fold motifs(FAD-binding GxGxxG and NADPH-binding GxGxxA), along with a central FMO recognition motif FxGxxxHxxxF/Y/W. These enzymes play a key role in regulating various metabolic routes and precisely modulate plant growth and development. Furthermore, the review summarizes the applications of Class B FPMOs of plants, showcasing through concrete examples their potential in synthesizing natural products such as auxins, indigo, and cyanogenic glycosides. These insights will broaden and deepen our understanding of FPMOs, fostering their transition from fundamental research to practical applications. More optimized biosynthetic pathways can be devised by leveraging FPMOs, conducive to the development of novel strategies and tools for agriculture, plant protection, natural product biosynthesis, and synthetic biology.
Biological Products/metabolism* ; Mixed Function Oxygenases/chemistry* ; Flavoproteins/chemistry* ; Plants/metabolism* ; Plant Proteins/chemistry* ; Cytochrome P-450 Enzyme System/genetics*

To investigate the pharmacological substances basis and anti-vitiligo mechanism of Carum carvi L. (caraway) fruits, chemical and blood-absorbed components were identified using mass spectrometry combined with literature study and database analysis. A “blood-absorbed components–target genes–pathways” network was constructed through network pharmacology. The pharmacological effects of Carum carvi L. extract and its key blood-absorbed component, acacetin, were validated in vitro. 72 chemical components were identified in the extract, with 11 prototype blood-absorbed components and 26 metabolites being detected in the plasma of SD rats. 14 key active components and 24 key targets were predicted. In vitro experiments demonstrated that acacetin at 10 μmol/L exhibited melanogenesis-promoting and tyrosinase-activating effects compared with the positive control, significantly upregulating the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (tyrosinase, TYR). This study comprehensively analyzes the chemical and blood-absorbed components of Carum carvi L. and elucidates its pharmacological substances basis, which provides a theoretical foundation for the anti-vitiligo effects of acacetin.

Osteonecrosis of the femoral head(ONFH)is a common orthopedic disease,and hip preservation surgery has high clinical value in the early stages of ONFH,especially for young and middle-aged patients.However,the repair of ONFH is heterogeneous,leading to inter-individual variations in the efficacy of hip preservation.Currently,the existing tissue-engineered scaffolds in the field of hip preservation are uncontrollable after implantation,making it difficult to achieve precise repair.Smart responsive materials have good biocompatibility and self-feedback capability.By combining them with therapeutic drugs to construct stimulus-responsive drug delivery systems,new possibilities are provided for the precise repair of ONFH.This paper reviews the research progress of smart responsive materials at home and abroad.Based on the response principles of various materials and the repair characteristics of ONFH,the application prospects of various smart responsive materials such as reactive oxygen species-responsive,fluid shear stress-responsive,and light/magnetic-responsive materials are discussed and prospected in the field of precise repair for ONFH,providing new ideas for the precise treatment of ONFH.

Objective To analyze the influence of drainage volume on prognosis of acute hydrocephalus(AHC)after aneurysmal subarachnoid hemorrhage(aSAH)by continuous lumbar drainage.Methods A retrospective trial was conducted on 82 AHC patients after aSAH admitted to the First Affiliated Hospital of Chongqing Medical University between January 2017 and January 2022.In 6 months after discharge,modified Rankin Scale(mRS)score was used to evaluate the prognostic outcomes.Univariate and multivariate logistic regression analyses were performed on demographic factors,severity of subarachnoid hemorrhage(SAH)at admission,medical history,cerebral vasospasm,and lumbar drainage data.Then a nomogram prediction model was constructed.Results Univariate analysis found that World Federation of Neurosurgical Societies(WFNS)score,Hunt-Hess grade,modified Fisher grade,time for continuous lumbar drainage,shunt dependence,cerebral vasospasm,and drainage volume were factors affecting the prognosis of the patients.Then logistic regression analysis revealed that high WFNS score(OR:3.25,95％CI:1.11～9.48),high modified Fisher grade(OR:3.66,95％CI:1.08～12.35),shunt dependence(OR:15.56,95％CI:1.22～198.57),and cerebral vasospasm(OR:22.24,95％CI:3.08～160.68)were independent predictors for mRS score,while volume of continuous lumbar drainage(OR:0.57,95％CI:0.40～0.82)was an independent protective factor.ROC curve analysis indicated a good predictive performance of the model(AUC=0.898,95％CI:0.935～0.861).Internal validation through Bootstrap method demonstrated excellent discriminatory ability of the model(C-index=0.950,95％CI:0.904～0.996;adjusted C-index:0.934).Conclusion Increased volume of lumbar drainage is an independent protective factor for poor prognosis following aSAH and can improve the prognosis of SAH patients.

Objective To analyze the risk factors and survival status of Epstein-Barr virus(EBV)infection in pa-tients with aplastic anemia(AA)after haploid allogeneic hematopoietic stem cell transplantation(Haplo-HSCT).Methods Clinical data of 78 AA patients who underwent Haplo-HSCT in the hematology department of a hospital from January 1,2019 to October 31,2022 were analyzed retrospectively.The occurrence and onset time of EBV viremia,EBV-related diseases(EBV diseases),and post-transplant lymphoproliferative disorders(PTLD)were ob-served,risk factors and survival status were analyzed.Results Among the 78 patients,38 were males and 40 were females,with a median age of 33(9-56)years old;53 patients experienced EBV reactivation,with a total inci-dence of 67.9％,and the median time for EBV reactivation was 33(13,416)days after transplantation.Among pa-tients with EBV reactivation,49 cases(62.8％)were simple EBV viremia,2 cases(2.6％)were possible EBV di-seases,and 2 cases(2.6％)were already confirmed EBV diseases(PTLD).Univariate analysis showed that age 1＜40 years old at the time of transplantation,umbilical cord blood infusion,occurrence of acute graft-versus-host disease(aGVHD)after transplantation,and concurrent cytomegalovirus(CMV)infection were independent risk fac-tors for EBV reactivation in AA patients after Haplo-HSCT.Multivariate analysis showed that concurrent CMV in-fection was an independent risk factor for EBV reactivation in A A patients after Haplo-HSCT(P=0.048).Ritu-ximab intervention before stem cell reinfusion was a factor affecting the duration of EBV reactivation(P＜0.05).The mortality of EBV viremia,EBV diseases,and PTLD alone were 8.2％,50.0％,and 100％,respectively.The 2-year overall survival rate of patients with and without EBV reactivation were 85.3％,and 90.7％,respectively,difference was not statistically significant(P=0.897).However,patients treated with rituximab had 2-year lower survival rate than those who did not use it,with a statistically significant difference(P=0.046).Conclusion EBV reactivation is one of the serious complications in AA patients after Haplo-HSCT,which affects the prognosis and survival of patients.

Objective:To explore the role of interleukin-18 (IL-18) in the pathogenesis of dermatomyositis (DM) associated with positive anti-melanoma differentiation-associated gene 5 antibodies(MDA5-DM).Methods:Twenty-eight cases of MDA5-DM in the department of rheumatology and immunology, the first hospital of Nanjing medical university and the first affiliated hospital od Wannan medical colledge from August 2018 to December 2011 were included in this study, comprising 15 cases with combined rapidly progressive interstitial pneumonia (RPILD) and 13 cases without RPILD (nonRPILD). Additionally, 28 cases of antisynthetase syndrome (ASS) and 28 healthy volunteers (HC) were included for comparison. Clinical, laboratory, and imaging data were collected for both the DM and ASS groups. Serum IL-18 levels were measured using ELISA. Independent t test, Mann-whitney U test, χ2 test and Fisher′s exact probability method were used for analysis. Results:Significant differences were observed in LDH, hydroxybutyrate dehydrogenase (HBDH), ESR, CRP, serum ferritin (SFE), and IL-18 levels between the MDA5-DM group, the ASS group and the HC group ( F=46.65, 43.19, 31.28, 23.94, 30.94, 49.44, all P<0.001). Additionally, lymphocyte counts and hemoglobin levels differed significantly among the three groups( F=35.26, P<0.001; F=18.59, P<0.001). MDA5-DM patients exhibited higher incidences of Gottron′s sign, helitrope rash, periungual erythema, skin ulcers, and RPILD compared to ASS patients ( χ2=20.96, P<0.001; χ2=5.85, P=0.016; χ2=13.69, P<0.001; χ2=9.16, P=0.002; χ2=4.79, P=0.029). However, the incidence of mechanic′s hand was lower in MDA5-DM patients ( χ2=3.90, P=0.048). The level of IL-18 significantly decreased in MDA5-DM after treatment[(104.28(71.96,151.10)pg/ml vs. 78.30(56.20, 94.80)pg/ml, =2.27, P=0.023)]. Similar reductions were observed in the ASS group[(72.30(61.39, 95.94)pg/ml vs. 45.30(29.00,84.10)pg/ml, Z=2.691, P=0.007]. The IL-18 level changes in the MDA5-DM combined with RPILD group were not statistically significant [99.49 (77.65, 130.87)pg/ml vs. 89.40(54.80, 120.20)pg/ml, Z=0.65, P=0.515]. In the MDA5-DM survival group, IL-18 levels decreased significantly after treatment [59.45(53.58, 81.63)pg/ml vs. 106.37(83.62, 152.07)pg/ml, Z=2.80, P=0.005], while the changes in the IL-18 levels of patients in the MDA5-DM death group were not statistically significant [99.49(56.70, 140.15)pg/ml vs. 94.80(71.40, 155.45)pg/ml, Z=1.75, P=0.080]. Conclusion:MDA5-DM patients are different from the ASS patients in clinical manifestations and indicators involved in laboratory tests. The expression level of IL-18 tends to increase during the active phase of MDA5-DM and ASS, and decrease with remission of the disease. MDA5-DM may play an important role in the pathogenesis, and persistent high level of IL-18 is responsible for RPILD and death of MDA5-DM. Sustained high level of IL-18 can be used as a potential biomarker for the estimating development of MDA5-DM into RPILD.

Objective:To establish a set of artificial intelligence (AI) verification rules for blood routine analysis.Methods:Blood routine analysis data of 18 474 hospitalized patients from the First Hospital of Jilin University during August 1st to 31st, 2019, were collected as training group for establishment of the AI verification rules,and the corresponding patient age, microscopic examination results, and clinical diagnosis information were collected. 92 laboratory parameters, including blood analysis report parameters, research parameters and alarm information, were used as candidate conditions for AI audit rules; manual verification combining microscopy was considered as standard, marked whether it was passed or blocked. Using decision tree algorithm, AI audit rules are initially established through high-intensity, multi-round and five-fold cross-validation and AI verification rules were optimized by setting important mandatory cases. The performance of AI verification rules was evaluated by comparing the false negative rate, precision rate, recall rate, F1 score, and pass rate with that of the current autoverification rules using Chi-square test. Another cohort of blood routine analysis data of 12 475 hospitalized patients in the First Hospital of Jilin University during November 1sr to 31st, 2023, were collected as validation group for validation of AI verification rules, which underwent simulated verification via the preliminary AI rules, thus performance of AI rules were analyzed by the above indicators. Results:AI verification rules consist of 15 rules and 17 parameters and do distinguish numeric and morphological abnormalities. Compared with auto-verification rules, the true positive rate, the false positive rate, the true negative rate, the false negative rate, the pass rate, the accuracy, the precision rate, the recall rate and F1 score of AI rules in training group were 22.7%, 1.6%, 74.5%, 1.3%, 75.7%, 97.2%, 93.5%, 94.7%, 94.1, respectively.All of them were better than auto-verification rules, and the difference was statistically significant ( P<0.001), and with no important case missed. In validation group, the true positive rate, the false positive rate, the true negative rate, the false negative rate, the pass rate, the accuracy, the precision rate, the recall rate and F1 score were 19.2%, 8.2%, 70.1%, 2.5%, 72.6%, 89.2%, 70.0%, 88.3%, 78.1, respectively, Compared with the auto-verification rules, The false negative rate was lower, the false positive rate and the recall rate were slightly higher, and the difference was statistically significant ( P<0.001). Conclusion:A set of the AI verification rules are established and verified by using decision tree algorithm of machine learning, which can identify, intercept and prompt abnormal results stably, and is moresimple, highly efficient and more accurate in the report of blood analysis test results compared with auto-vefication.

ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma （HCC） and its relationship with prognosis， clinical stage and immune infiltration. MethodsIn this study， TCGA， GTEx， TIMER2.0， HPA database and qRT-PCR， western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages； Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC； the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC； the STRING database was used to detect the protein binding with FANCI； the TCGA and GTEx databases were used for GO and KEGG enrichment analysis； Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues， the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated （P<0.001）； and HCC patients with high expression of FANCI had poor prognosis （P<0.001）； the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4⁺ T cells， the number of Th2 cells and the expression of immune checkpoints， and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group （P<0.01）； GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity； Cell experiments showed that knockdown of FANCI could inhibit the proliferation， invasion and migration of HCC （P<0.05）. ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues， which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport， and is associated with poor prognosis. The proliferation， invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.

This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1β, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.
Animals ; Rats ; Caspase 1/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Interleukin-18 ; Blood Glucose ; Pyroptosis ; Tumor Necrosis Factor-alpha ; Diabetes Complications ; Vascular Diseases ; Inflammasomes ; Cholesterol ; Lipids ; Diabetes Mellitus