Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective:To evaluate the effect of combining contralateral high-frequency transcranial magnetic stimulation (rTMS) with biofeedback-controlled empty swallowing training on dysphagia among stroke survivors.Methods:Eighty dysphagic stroke survivors were divided at random into a control group, a biofeedback group, an rTMS group and a combined treatment group, each of 20. In addition to routine dysphagia rehabilitation, the biofeedback group and the rTMS group received empty swallowing training based on biofeedback or high-frequency rTMS applied to the healthy motor cortex as appropriate. The combined treatment group was given both. The treatment was administered once daily, 5 days a week for 3 consecutive weeks. Before and after the treatment, all of the subjects′ swallowing was evaluated using the penetration aspiration scale (PAS), functional oral intake scale (FOIS) and a standardized swallowing assessment (SSA). The latency and amplitude of the mylohyoid muscle′s motor evoked potentials (MEPs) were also recorded before and after the treatment.Results:After the treatment, significant improvement was observed in the average PAS, FOIS and SSA scores as well as in the latency and amplitude of the MEPs in the four groups. The average results in the combined treatment group were significantly better than in the other 3 groups. The latency of the mylohyoid muscle′s MEP was significantly shorter in the combined group than in the control and biofeedback groups on average, while the amplitude was significantly greater than in the control group.Conclusion:Combining contralateral high frequency rTMS with empty swallowing training based on biofeedback can better improve the swallowing of dysphagic stroke survivors.

AIM:To investigate the effects of sodium selenite(SS)on viability,migration and angiogenesis of human non-small-cell lung cancer(NSCLC)H520 and A549 cells.METHODS:The H520 cells,A549 cells,and hu-man umbilical vein endothelial cells(HUVEC)were divided into control group(0 μmol/L SS),low dose group(5 μmol/L SS),middle dose group(10 μmol/L SS),and high dose group(20 μmol/L SS).Cell viability was assessed using the CCK-8 assay,and the half-maximal inhibitory concentration(IC50)was calculated.Cell migration and invasion abilities were determined through wound healing and Transwell assays.The regulatory effects of SS on angiogenesis,vasculogenic mimicry and"mosaic"vascular formation between HUVEC and NSCLC cells were detected using vessel forming assays.The expression of vascular endothelial growth factor(VEGF)in the supernatant of lung cancer cells in each group was de-tected using chemiluminescence.RT-qPCR was used to assess the mRNA expression of VEGF,vascular endothelial growth factor receptor 2(VEGFR2)and angiotensin II(Ang II).Western blot was used to examine the protein levels of VEGF,p-PI3K,and p-Akt in H520 and A549 cells.RESULTS:The IC50 values of SS to HUVEC,A549 cells and H520 cells for 48 h were 6.762,9.003 and 7.356 μmol/L,respectively.Compared with control group,the wound healing rate was significantly decreased in each group treated with SS for 48 h(P<0.01).In HUVEC,the number of migrating cells in middle dose and high dose groups decreased(P<0.01),whereas in lung cancer cells,the number of migrating cells in each group decreased after SS treatment(P<0.01).The mRNA expression levels of VEGF,VEGFR2 and Ang II were lower in high-dose SS group than those in control group(P<0.05 or P<0.01).In H520 cells,compared with control group,the protein levels of VEGF,p-PI3K and p-Akt in SS treatment groups were significantly decreased(P<0.05 or P<0.01).CONCLUSION:Sodium selenite inhibits the viability and migration of HUVEC,H520 cells and A549 cells,and inhibits the formation of vasculogenic mimicry and mosaic vessels in NSCLC cells.This mechanism may be related to the inhibition of PI3K-Akt signaling pathway activation and regulation of VEGF.

Objective:To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT.Methods:Nineteen patients with IFR after allo-HSCT at Peking University People’s Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) .Results:Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10–59) years. The median IFR onset time was 68 (9–880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation ( P=0.021) , hemorrhagic cystitis after transplantation ( P=0.012) , delayed platelet engraftment ( P=0.008) , and lower transplant mononuclear cell count ( P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively ( P<0.01) . Conclusion:Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an independent risk factor for colorectal cancer (CRC), and the patients with CRC and T2DM have worse survival. The human gut microbiota (GM) is linked to the development of CRC and T2DM, respectively. However, the GM characteristics in patients with CRC and T2DM remain unclear. METHODS: We performed fecal metagenomic and targeted metabolomics studies on 36 samples from CRC patients with T2DM (DCRC group, n = 12), CRC patients without diabetes (CRC group, n = 12), and healthy controls (Health group, n = 12). We analyzed the fecal microbiomes, characterized the composition and function based on the metagenomics of DCRC patients, and detected the short-chain fatty acids (SCFAs) and bile acids (BAs) levels in all fecal samples. Finally, we performed a correlation analysis of the differential bacteria and metabolites between different groups. RESULTS: Compared with the CRC group, LefSe analysis showed that there is a specific GM community in DCRC group, including an increased abundance of Eggerthella , Hungatella , Peptostreptococcus , and Parvimonas , and decreased Butyricicoccus , Lactobacillus , and Paraprevotella . The metabolomics analysis results revealed that the butyric acid level was lower but the deoxycholic acid and 12-keto-lithocholic acid levels were higher in the DCRC group than other groups ( P < 0.05). The correlation analysis showed that the dominant bacterial abundance in the DCRC group ( Parvimonas , Desulfurispora , Sebaldella , and Veillonellales , among others) was negatively correlated with butyric acid, hyodeoxycholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, chenodeoxycholic acid, cholic acid and glycocholate. However, the abundance of mostly inferior bacteria was positively correlated with these metabolic acid levels, including Faecalibacterium , Thermococci , and Cellulophaga . CONCLUSIONS Unique fecal microbiome signatures exist in CRC patients with T2DM compared to those with non-diabetic CRC. Alterations in GM composition and SCFAs and secondary BAs levels may promote CRC development.
Humans ; Gastrointestinal Microbiome/genetics* ; Diabetes Mellitus, Type 2 ; Microbiota ; Bacteria/genetics* ; Fatty Acids, Volatile ; Colorectal Neoplasms/metabolism* ; Butyrates ; Feces/microbiology*

Klebsiella pneumoniae can cause a variety of infectious diseases, especially in immunocompromised population. The emergence of multidrug-resistant hypervirulent Klebsiella pneumoniae has greatly limited the choice of treatment for Klebsiella pneumoniae infection, and the exploration of new treatment strategies is imminent. In the process of infection, there is a complex interaction between the programmed cell death of host cells and the invasion of Klebsiella pneumoniae. This paper mainly reviewed the research progress in several mechanisms of programmed cell death such as pyroptosis, apoptosis, necroptosis and autophagy caused by Klebsiella pneumoniae.

Objective:To evaluate the effect of sitagliptin on the expression of airway mucin 5AC (MUC5AC) in mice with endotoxin-induced lung injury.Methods:Thirty-six healthy male SPF C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), endotoxin-induced lung injury group (group L), and endotoxin-induced lung injury+ sitagliptin group (group S). Lipopolysaccharide (LPS) 3 mg/kg was intratracheally infused to prepare endotoxin-induced lung injury model in L and S groups, while the equal volume of normal saline was given instead in group C. Sitagliptin 100 mg/kg was intraperitoneally injected at 1 h before LPS infusion in group S, and normal saline was intraperitoneally injected at 1 h before endotracheal infusion in C and L groups. The arterial blood samples from femoral artery were taken at 24 h of LPS or normal saline infusion for measurement of PaO 2 and glucose levels.The mice were then sacrificed, and broncho-alveolar lavage fluid (BALF) and lung tissues were collected for determination of the concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α)in serum and BALF (by enzyme-linked immunosorbent assay), wet/dry weight ratio (W/D ratio), expression of MUC5AC (by immunohistochemistry and immunohistochemical comprehensive score), and expression of MUC5AC mRNA in lung tissues (by quantitative real-time polymerase chain reaction) and for examination of the pathological changes of lung tissues (using haematoxylin and eosin staining) which were scored. Results:Compared with group C, PaO 2 was significantly decreased, the glucose levels, W/D ratio and lung injury score were increased, the concentrations of IL-6, IL-1β and TNF-α in serum and BALF were increased, and the expression of MUC5AC mRNA in lung tissues was up-regulated in L and S groups( P<0.05). Compared with group L, PaO 2 was significantly increased, the glucose levels, W/D ratio and lung injury score were decreased, the concentrations of IL-6, IL-1β and TNF-α in serum and BALF were decreased, and the expression of MUC5AC mRNA in lung tissues was down-regulated in group S( P<0.05). Conclusions:The mechanism by which sitagliptin alleviates endotoxin-induced lung injury is related to down-regulation of MUC5AC expression in mice.

Objective:To investigate the efficacy and safety of intracavernous sinus spring coil+Onyx gel embolization combined with proximal spring coil occlusion of the ophthalmic vein in cavernous sinus-dural arteriovenous fistula (CS-DAVF).Methods:Thirty-seven patients with CS-DAVF accepted intracavernous sinus spring coil+Onyx gel embolization combined with proximal spring coil occlusion of ophthalmic vein in Department of Radiology and Interventional Medicine, First Affiliated Hospital of Zhengzhou University were selected. The clinical data and therapeutic efficacy of these patients were retrospectively analyzed.Results:All 37 patients had different degrees of ocular symptoms at the time of treatment: 31 (83.8 %) had conjunctival congestion, 16 (43.2 %) had exophthalmos, and 14 (37.8 %) had obvious periorbital vascular murmur. Endovascular intervention was performed in all patients via venous routes, including inferior petrous sinus approach ( n=34), ophthalmic vein approach ( n=2), and facial vein approach ( n=1). Immediate postoperative DSA showed that 31 patients had complete occlusion of the fistula, and 6 patients had near-total occlusion (disappeared drainage of the thickened ophthalmic vein or obviously slowed down drainage). Thirty-five patients had ocular oedema of varied degrees and then gradually reduced (lasting for 1-2 weeks), and all the ocular congestion and vascular murmurs disappeared before discharging from the hospital. Four patients had postoperative palsy of the motor and abducens nerves, which improved significantly after 1-5 months; 1 patient had diplopia in combination with abducens nerve palsy; all symptoms alleviated after 2 months of nutritional nerve medication. Follow up in Outpatient Clinic or telephone was performed for (12.1±4.4) months, ranged for 6.5-21.3 months; symptoms of ocular congestion and edema disappeared in all patients at the last follow-up. Followed-up DSA at 6 months showed no recurrence of CS-DAVF. Conclusion:Intracavernous sinus spring coil+Onyx gel embolisation combined with proximal spring coil occlusion of the ophthalmic vein is safe and effective in CS-DAVF.

Objective To investigate the effect of galectin-1 preconditioning on pyroptosis of venti-lator-induced lung injury(VILI)in mice.Methods Thirty clean grade healthy male C57BL/6 mice,aged 6-8 weeks,weighing 22-30 g,were divided into three groups by random number table method:control group(group C),VILI group(group V),and galectin-1+VILI group(group G),10 mice in each group.After endotracheal intubation,group C kept spontaneous breathing for 4 hours,groups V and G kept me-chanical ventilation for 4 hours.One hour before endotracheal intubation,groups C and V were intraperito-neally injected with normal saline 0.75 ml,and group G was intraperitoneally injected with galectin-1 3 μg.Arterial blood was collected before endotracheal intubation and after spontaneous respiration or ventilation to detect PaO2.Then mice were sacrificed and bronchoalveolar lavage fluid(BALF)was collected.Concentra-tions of IL-1β and IL-18 in BALF were detected by ELISA.Lung tissue was collected for determination of the wet weight/dry weight ratio(W/D).The expression of GSDMD,caspase-1,and caspase-11 mRNA and protein in lung tissues were detected by qRT-PCR and Western blot.Pathological changes of the lungs were observed and scored by HE staining.Results Compared with group C,PaO2 were significantly decreased,W/D,concentrations of IL-1β and IL-18 in BALF,mRNA and protein expressions of GSDMD,caspase-1 and caspase-11,and lung injury score were significantly increased in groups V and G(P＜0.05).Com-pared with group V,PaO2 was significantly increased,W/D,concentrations of IL-1β and IL-18 in BALF,mRNA and protein expressions of GSDMD,caspase-1,and caspase-11,and lung injury score were signifi-cantly decreased in group G(P＜0.05).Conclusion Galectin-1 can increase PaO2 in mice and reduce IL-1β and IL-18 concentration,mRNA expression and protein content of classical non-classical pyroptosis pathway related genes,and reduce VILI in mice.

Objective This paper summarizes the research progress of biosynthesis and pharmacological effects of podophyllotoxin drugs,in order to provide reference for the wide application of these drugs.Methods The plant source,chemical structure,action mechanism and synthesis pathway of podophyllotoxin drugs were summarized.The pharmacological and toxicological characteristics and mechanisms of these drugs were discussed,and the research progress of new dosage forms of podophyllotoxin drugs was reviewed.Results Podophyllotoxin and its derivatives are important chemical constituents in the plants of the podophyllum,such as Dysosma versipellis,Diphylleia sinensis,Sinopodophyllum hexandrum.This kind of drug has few natural sources and can be artificially produced through chemical and biosynthetic pathways.Podophyllotoxin drugs have pharmacological effects such as anti-inflammatory,anti-tumor and anti-virus,but their toxic effects need to be paid attention to.Drugs can be transported by carriers to reduce toxicity and increase effect.Conclusion Podophyllotoxin drugs have broad clinical application prospects,and will be further studied and applied in the fields of anti-inflammatory,anti-tumor and anti-virus in the future.