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.

ObjectiveTo develop a scientifically rigorous and contextually appropriate instrument for evaluating the health service experience of pulmonary tuberculosis patients in China, to enable systematic assessment of core medical care dimensions, and to provide quantitative evidence for service improvement. MethodsGrounded in the theoretical framework of healthcare accessibility and the clinical care pathway for tuberculosis patients, the tool was developed through a systematic literature review and the Delphi expert consultation method. A multi-stage cluster sampling strategy was employed to survey pulmonary tuberculosis patients who had been receiving treatment for more than two months, aimed to explore the scale’s applicability in real-world settings. Reliability was assessed using Cronbach’s α and split-half reliability coefficients. Validity was evaluated through content validity, structural validity, convergent validity, and discriminant validity. ResultsThe tool was composed of 21 items across four dimensions: awareness, accessibility, affordability, and acceptability of tuberculosis medical care. It demonstrated a Cronbach’s α coefficient of 0.838 and a split-half reliability coefficient of 0.859. Exploratory factor analyses extracted six factors: satisfaction with healthcare services, supportive role of nurses, affordability of treatment costs, doctor-patient communication, waiting time for medical appointments, and transportation cost. The goodness-of-fit index (GFI) and other indices met the recommended standards, with the loading matrix indicating robust structural validity of the tool. The constructed factor model exhibited satisfactory content validity and discriminant validity. ConclusionThe scale for assessing patients’ experiences with tuberculosis-related medical care developed in this study demonstrates good reliability and validity and serves as a practical tool for evaluating patient experiences of tuberculosis medical care in China.

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.

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.

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.

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 summarize the construction and practice of the compulsory postgraduate course "reproductive genetics in gynecology and obstetrics" in Department of Gynecology and Obstetrics, Peking University, and to evaluate the teaching effect of this course.Methods:A total of 139 postgraduates who studied in Department of Obstetrics and Gynecology, Peking University, from 2019 to 2021 were enrolled as subjects, and a syllabus was constructed through a top-level design based on the "biological-psychological-social medicine pattern", with the teaching objectives of reproductive genetics theory, clinical translation, genetic counseling methods, and research advances. The teaching effect was evaluated by analyzing teaching assessment results, teaching evaluation feedback, and teaching achievements. SPSS 26.0 software was used to perform the t-test and the chi-square test. Results:The written test score, usual performance score, and total score of the postgraduate students in 2021 were higher than those in 2019 and 2020 [(73.50±8.19) vs. (70.94±14.90); (68.60±2.82) vs. (68.22±4.58); (90.58±4.18) vs. (89.49±7.60)], with significant differences in written test score and total score ( P<0.05). There was a high degree of satisfaction with the feedback of teaching, and 85.61% (119/139) of the students selected "great satisfaction"; in particular, there were increases in the degree of satisfaction with expanding research ideas and reflecting the advances in this discipline, but with no significant difference. There was a significant increase in the number of published articles. Conclusion:For the active implementation of the course of "Reproductive Genetics in Obstetrics and Gynecology", improving the teaching process in a planned and step-by-step way through a top-level design in advance can help to expand research ideas for future research work among postgraduates in obstetrics and gynecology and promote the sustainable development and improvement of the teaching of the emerging interdisciplinary discipline of reproductive genetics in obstetrics and gynecology.