Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, its therapeutic potential and mechanisms against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we evaluated the in vivo neuroprotective effects of indobufen through both pretreatment and posttreatment regimens in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In vitro, human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were employed to investigate the relationship between indobufen and the pyroptosis-associated NF-κB/Caspase-1/GSDMD pathway. The pharmacodynamic tests revealed that indobufen ameliorated I/R injury by decreasing the level of thromboxane B2 (TXB2), infarct size, brain edema and neurological impairment in rats and rescuing cell pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by regulating the NF-κB/Caspase-1/GSDMD pathway. Overall, these studies indicate that indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

This study employed bioinformatics to screen the feature genes related to efferocytosis in diabetic kidney disease(DKD) and explores traditional Chinese medicine(TCM) regulating these feature genes. The GSE96804 and GSE30528 datasets were integrated as the training set, and the intersection of differentially expressed genes and efferocytosis-related genes(ERGs) was identified as DKD-ERGs. Subsequently, correlation analysis, protein-protein interaction(PPI) network construction, enrichment analysis, and immune infiltration analysis were performed. Consensus clustering was conducted on DKD patients based on the expression levels of DKD-ERGs, and the expression levels, immune infiltration characteristics, and gene set variations between different subtypes were explored. Eight machine learning models were constructed and their prediction performance was evaluated. The best-performing model was evaluated by nomograms, calibration curves, and external datasets, followed by the identification of efferocytosis-related feature genes associated with DKD. Finally, potential TCMs that can regulate these feature genes were predicted. The results showed that the training set contained 640 differentially expressed genes, and after intersecting with ERGs, 12 DKD-ERGs were obtained, which demonstrated mutual regulation and immune modulation effects. Consensus clustering divided DKD into two subtypes, C1 and C2. The support vector machine(SVM) model had the best performance, predicting that growth arrest-specific protein 6(GAS6), S100 calcium-binding protein A9(S100A9), C-X3-C motif chemokine ligand 1(CX3CL1), 5'-nucleotidase(NT5E), and interleukin 33(IL33) were the feature genes of DKD. Potential TCMs with therapeutic effects included Astragali Radix, Trionycis Carapax, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma, which mainly function to clear heat, replenish deficiency, activate blood, resolve stasis, and promote urination and drain dampness. Molecular docking revealed that the key components of these TCMs, including β-sitosterol, quercetin, and sitosterol, exhibited good binding activity with the five target genes. These results indicated that efferocytosis played a crucial role in the development and progression of DKD. The feature genes closely related to both DKD and efferocytosis, such as GAS6, S100A9, CX3CL1, NT5E, and IL33, were identified. TCMs such as Astragali Radix, Trionycis Carapa, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma may provide a new therapeutic strategy for DKD by regulating efferocytosis.
Humans ; Computational Biology ; Diabetic Nephropathies/physiopathology* ; Protein Interaction Maps ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Phagocytosis/genetics* ; Efferocytosis

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Objective:To analyze the differences in endoscopic and pathological features in autoimmune gastritis (AIG) patients with and without Helicobacter pylori ( HP) infection, and to explore the effects of HP on the clinical manifestations and disease development in AIG patients. Methods:From January 2022 to April 2024, 174 AIG patients who visited Beijing Hospital and met the 2022 AIG diagnostic criteria established by Japanese Gastroenterological Endoscopy Society were enrolled and divided into the HP-infected group (including current and previous infection, 77 cases) and the HP-unifected group (97 cases). The general clinical data, laboratory examinations endoscopic findings, and pathological characteristics of the two groups were analyzed. Independent sample t-test and chi-square test were used for statistical analyses. Results:The vitamin B 12 level of HP-infected group was higher than that of HP-unifected group ((573.81±460.77) ng/L vs. (411.86±335.00) ng/L), and the difference was statistically significant ( t=-2.57, P=0.011). The average red blood cell volume of HP-infected group was lower than that of HP-unifected group ((87.30±8.86) fL vs. (98.50±49.82) fL), and the difference was statistically significant ( t=2.16, P=0.033). The proportion of intestinal metaplasia in gastric fundus in HP-infected group was lower than that in HP-unifected group (50.6% (39/77) vs. 73.2% (71/97)), and the difference was statistically significant ( χ2=9.38, P=0.002). Conclusion:HP infection in AIG patients may delay the malabsorption of vitamin B 12 and the occurrence of intestinal metaplasia in gastric fundus.

BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

This study aimed to compare the ameliorative effects of Lycii Fructus and Chrysanthemi Flos at different ratios on retinal damage in mice and to elucidate the underlying mechanisms. A retinal injury model was established by intraperitoneal injection of sodium iodate(NaIO_3) solution. The mice were divided into the following groups: blank group, model group, positive drug(AREDS 2) group, low-and high-dose groups of Lycii Fructus and Chrysanthemi Flos at 1∶1, low-and high-dose groups at 3∶1, and low-and high-dose groups at 1∶3. Administration was carried out 15 days after modeling. The visual acuity of the mice was assessed using the black-and-white box test. The fundus was observed using an optical coherence tomography device, and retinal thickness was measured. HE staining was used to observe the morphology and pathological changes of the retina. The levels of oxidative factors in serum and ocular tissues were measured using assay kits. The levels of inflammatory factors in serum and ocular tissues were detected by enzyme-linked immunosorbent assay(ELISA), and the expression of Nrf2, HO-1, and NF-κB proteins in ocular tissues was analyzed by Western blot. The results showed that after administration of Lycii Fructus and Chrysanthemi Flos at different ratios, the model group showed improved retinal thinning and disordered arrangement of retinal layers, elevated content of SOD and GSH in the serum and ocular tissues, and reduced levels of MDA, TNF-α, IL-1β, and IL-6. Lycii Fructus and Chrysanthemi Flos at 1∶1 and 1∶3 showed better improvement effects. The combination significantly upregulated the expression levels of Nrf2 and HO-1 and downregulated the expression of NF-κB p65. These results indicate that Lycii Fructus and Chrysanthemi Flos at different ratios can improve retinal damage, reduce oxidative stress, and alleviate inflammation in both the body and ocular tissues of mice. The mechanism may be related to the regulation of the Nrf2/HO-1 and NF-κB signaling pathways in ocular tissues. These findings provide a theoretical basis for the clinical application of Lycii Fructus and Chrysanthemi Flos in the treatment of dry age-related macular degeneration.
Animals ; Mice ; Retina/injuries* ; Male ; Lycium/chemistry* ; Drugs, Chinese Herbal/administration & dosage* ; Chrysanthemum/chemistry* ; NF-kappa B/genetics* ; Humans ; Retinal Diseases/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress/drug effects* ; Flowers/chemistry* ; Heme Oxygenase-1/genetics*

Foodborne illnesses caused by Salmonella pose significant threats to worldwide public health safety.In this study,a rapid method for screening viable Salmonella in oyster sauce and milk was developed by utilizing an electronic microbial growth analyzer(EMGA).Target food samples were diluted 10-fold with RVS broth and loaded into test tubes.Test tubes were positioned in the EMGA to determine the bacterial growth curves and the time required to reach the maximum growth rate(Tmgr).Using Salmonella typhimurium(S.typhimurium)asan model species,there was linear relationship between the logarithmic value of viable bacterial concentration(lgC)and Tmgr over the range of 5×101-5×106 CFU/mL,with a detection limit of 10 CFU/mL.For oyster sauce,the regression equation was Tmgr(min)=-80.775lg[C/(CFU/mL)]+754.96(R2=0.9907),and the recovery rates of S.typhimurium ranged from 95.2%to 119.8%,with relative standard deviations(RSD)ranging from 3.5%to 16.3%.For milk,the regression equation was Tmgr(min)=-71.922 lg[C/(CFU/mL)]+618.65(R2=0.9985),with recovery rates ranging from 98.4%to 110.6%and RSD ranging from 6.4%to 12.8%.The EMGA method required only one portable instrument,and involving only three manual steps,i.e.,dilution,transfer,and insertion.When S.typhimurium contamination reached 106 CFU/mL,the total time consumption,from the unwrapping of samples to the readout of bacterial concentration,was no more than 7 h.When applied to detection of actual oyster sauce and milk samples,the new method demonstrated strong consistency with plate counting results in positive detection rates.This method was superior to the plate counting method,which was generally considered as a gold standard,in terms of accuracy,precision,simplicity and efficiency,representing a promising alternative for the on-site screening and quantification of viable Salmonella in oyster sauce and milk products.

Objective:To explore the perioperative safety and postoperative efficacy of prophylactic jejunal nutrition tube placement during early gastric body cancer pylorus-preserving gastrectomy (PPG).Methods:The clinical data of 29 gastric cancer patients treated by Beijing Friendship Hospital, Capital Medical University from January 2018 to December 2024 were retrospectively analyzed. There were 17 males (58.6%) and 12 females (41.4%), aged from 43 to 74 years, with an average age of (58.9 ± 8.3) years, and an average body mass index (BMI) of (24.3 ± 3.0) kg/m 2. According to the type of catheterization, all cases were divided into jejunal nutrition tube group ( n=12) and gastric tube group( n=17). The main outcome was the incidence of delayed gastric emptying within one month after surgery in both groups. Statistical analysis was conducted using SPSS26.0 software. Results:Patients in the jejunal feeding tube group resumed oral liquid intake, soft diet and regular diet significantly earlier postoperatively compared to those in the gastric tube group, with statistically significant differences ( P<0.05). Conversely, the time to removal of the tube was significantly earlier in the gastric tube group than in the jejunal feeding tube group ( P<0.05). However, the proportion of patients requiring reinsertion of a gastric or jejunal feeding tube postoperatively was significantly higher in the gastric tube group (7 cases) compared to the jejunal feeding tube group (0 case) ( P<0.05). In the jejunal feeding tube group, there were 4 cases occurred DGE, in the gastric tube group, there were 8 cases occurred DGE. There were no statistically significant differences between the two groups in either the overall incidence of DGE or the distribution of DGE severity grades. On postoperative 7th day , the Gastric Outlet Obstruction Scoring System (GOOSS) grade was significantly better in the jejunal feeding tube group than in the gastric tube group ( P<0.05), and all patients in the jejunal feeding tube group had resumed liquid intake, compared to only 58.8% in the gastric tube group. Conclusions:Compared with gastric tube placement, intraoperative prophylactic jejunal feeding tube placement for PPG has significant advantages in perioperative safety and postoperative recovery, but large-sample prospective studies are still needed for further verification.

Objective To explore the neuro-protective effect of remimazolam(Rem)on traumatic brain injury(TBI)in rat models.Methods A TBI rat model was constructed.The rats were randomly divided into control group,traumatic brain injury group(TBI group),low-dose and high-dose remimazolam groups(Rem-L,Rem-H groups),and high-dose remimazolam+Jagged1 group(Rem-H+Jagged1 group),with 12 rats in each.All rats were evaluated for neurological deficits.The serum level of inflammatory factors like tumor necrosis factor α(TNF-α)and interleukin-1β(IL-1β)were detected by ELISA.HE staining microscopy was used to observe the changes of brain histopathology.The expression of glial fibrillary acidic protein(GFAP)and ionized calcium-binding adaptation molecule 1(IBA1)were detected by immunohistochemistry.Western blot was applied to detect the ex-pression of Notch,Notch 1 intracellular domain(NICD)and Hes-1 protein in the brain tissue.Results Compared with the control group,the TBI group showed a larger area of brain tissue defect and edema,with more activated glial cells and fragmented,concentrated and deeply stained neuronal nuclei,indistinct nucleoli,deeply stained cy-toplasm,and partial neuronal necrosis The neurological deficit score was higher,level of TNF-α and IL-1β and the expression of GFAP,IBA1,Notch,NICD,and Hes-1 all elevated(P＜0.05).Remazolam reduced brain tissue defect area,alleviated edema,inhibited glial cell activation and neuronal apoptosis,and reduced nerve function deficit score,the level of TNF-α and IL-1β,and the expression of GFAP,IBA1,Notch,NICD and Hes-1(P＜0.05).Jagged1 could aggravate brain tissue injury,increase neural function deficit score,levels of TNF-α and IL-1β and expressions of GFAP,IBA1,Notch,NICD and Hes-1(P＜0.05).Conclusions Remimazolam may have neuroprotective effects as shown by TBI rat models,and the underlying mechanism is potentially related to the inhibition of the Notch/Hes-1 signaling pathway.