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.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the effect and mechanism of macrophage colony stimulating factor(M-CSF)on myocardial function after acute myocardial infarction(AMI)in mice by regulating cardiac macrophages.Methods Fifty C57mice were randomly di-vided into Sham Group(n=10,sham operation group),MI Group(n=20,AMI model was prepared,and normal saline was injected in-traderitoneally)and MM Group { n=20,AMI model was prepared,and M-CSF reagent[500μg/(kg·d)]was injected intraderitoneal-ly}.At the end of the experiment,after completing a cardiac ultrasound,the myocardial tissue was collected,interleukin-4(IL-4),interleukin-6(IL-6),monocyte ehemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),interferon-α(IFN-α),atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),Collagen Ⅰ and Collagen Ⅲ were detected by enzyme-linked immunosorbent assay(ELISA),the apoptosis-related proteins Bax,C-caspase-3,caspase-3,nuclear transcription facter(NF)-κB p65,transduction and activator of transcription 3(STAT3),transduction and activator of transcription 6(STAT6)were detected by Western blot assay,and the neovascularization markers in MI peripheral area were determined by immunohis-tochemistry,the expression levels of M1-type macrophages and M2-type macrophages were detected by flow cytometry.Results The left ventricular size and left ventricular ejection fraction(LVEF)were significantly improved in MM Group when compared with the MI Group,and the indexex of myocardial inflammation,hypertrophy,apoptosis,and fibrosis decreased significantly(P＜0.05).The expres-sion of neovascularization mardker CD31 was significantly up-regulated in MM Group.The expression of M2macrophage in MM group was significantly higher than when compared with the MI group,while the level of M1 macrophage was lower(P＜0.05).The expression of NF-κB p65 in MI group was statistically higher than that in the Sham group and MM group,while the levels of STAT3 and STAT6 were higher in the MM group than in the MI group(P＜0.05).Conclusion M-CSF can inhibit inflammatory response,reduce myo-cardial fibrosis,hypertrophy and apoptosis,promote angiogenesis,inhibit M1-type macrophages and up-regulate the expression of M2-type macrophages to promote myocardial tissue repair and improve ventricular structural remodeling,in which NF-κB/STAT signa-ling pathway plays an important role.

Objective:To investigate the epidemiological characteristics of human respiratory syncytial virus (HRSV) in patients with Severe Acute Respiratory Infection (SARI) in Tianjin from 2015 to 2020.Methods:The study data were obtained from the Third Center Hospital of Tianjin, a designated sentinel hospital, from 2015 to 2020, with 1 597 SARI patients enrolled in this study. The clinical specimens of the research participants were subjected to respiratory multi-pathogen testing. HRSV-positive specimens were subtyped to analyze the differences in HRSV detection rates among cases of different age groups and periods and their mixed infection situations.Results:A total of 1 597 nasopharyngeal swabs were collected, with an HRSV detection rate of 4.20%. Among 67 HRSV-positive specimens, there were 19 pure HRSV-A nucleic acid-positive specimens, 19 pure HRSV-B nucleic acid-positive specimens and 29 mixed HRSV-A and HRSV-B nucleic acid-positive specimens. The difference in HRSV detection rate among different age groups was statistically significant ( P<0.05), and the HRSV detection rate in children under five years old was higher than that in other age groups. From 2016 to 2020, the detection rate of HRSV showed an increasing trend year by year. The HRSV detection rate of SARI cases was highest in the winter season, at 7.15%. There were 10 (14.93%) mixed positive cases for HRSV and other viruses, of which four were mixed positive for HRSV and influenza A. Conclusion:The incidence of HRSV in Tianjin exhibits an increasing trend from 2016 to 2020, peaking during the winter season, with children under five years old constituting a high-risk demographic for HRSV infection.

Objective:To investigate the epidemiological characteristics of human respiratory syncytial virus (HRSV) in patients with Severe Acute Respiratory Infection (SARI) in Tianjin from 2015 to 2020.Methods:The study data were obtained from the Third Center Hospital of Tianjin, a designated sentinel hospital, from 2015 to 2020, with 1 597 SARI patients enrolled in this study. The clinical specimens of the research participants were subjected to respiratory multi-pathogen testing. HRSV-positive specimens were subtyped to analyze the differences in HRSV detection rates among cases of different age groups and periods and their mixed infection situations.Results:A total of 1 597 nasopharyngeal swabs were collected, with an HRSV detection rate of 4.20%. Among 67 HRSV-positive specimens, there were 19 pure HRSV-A nucleic acid-positive specimens, 19 pure HRSV-B nucleic acid-positive specimens and 29 mixed HRSV-A and HRSV-B nucleic acid-positive specimens. The difference in HRSV detection rate among different age groups was statistically significant ( P<0.05), and the HRSV detection rate in children under five years old was higher than that in other age groups. From 2016 to 2020, the detection rate of HRSV showed an increasing trend year by year. The HRSV detection rate of SARI cases was highest in the winter season, at 7.15%. There were 10 (14.93%) mixed positive cases for HRSV and other viruses, of which four were mixed positive for HRSV and influenza A. Conclusion:The incidence of HRSV in Tianjin exhibits an increasing trend from 2016 to 2020, peaking during the winter season, with children under five years old constituting a high-risk demographic for HRSV infection.

Respiratory virus infections spread quickly, and some diseases are even more likely to cause a global epidemic. In order to explore how better to carry out surveillance of viral respiratory infectious diseases, the author searched the surveillance situation of key viral respiratory infectious diseases in America, Europe, and China, et al., then put forward several suggestions such as strengthening application of information technology, broaden monitoring channels, building early monitoring and early warning mechanisms.

Influenza imposes a significant disease burden on society and individuals annually, and influenza vaccination is considered a significant public health measure to prevent influenza and reduce influenza-related severe disease and death. The low influenza vaccination rate in China is partly due to certain factors affecting the willingness and behavior of individuals to receive them. Scientific research and targeted interventions on these factors can effectively improve the vaccination situation. Commonly used individual-level theoretical models for influenza vaccination behavior include the health belief model, protection motivation theory, and theory of planned behavior. This study reviews theoretical models commonly employed in researching influenza vaccination willingness and behavior. An overview of these practical applications and challenges models is presented to provide references for relevant research and intervention programs in China.

Objective To investigate the predictive value of preoperative fibrinogen/albumin ratio (FAR) and systemic immune inflammation index (SII) on the postoperative prognosis of patients with pancreatic ductal adenocarcinoma. Methods An ROC curve was used in determining the best cutoff values of FAR and SII and then grouped. The Cox proportional hazards model was used in analyzing the prognostic factors of radical pancreatic cancer surgery, and then a Nomogram prognostic model was established. C-index, AUC, and calibration curve were used in evaluating the discrimination and calibration ability of the Nomogram. DCA curves were used in assessing the clinical validity of the Nomograms. Results The optimal cutoff values for preoperative FAR and SII were 0.095 and 532.945, respectively. FAR≥ 0.095, SII≥ 532.945, CA199≥ 450.9 U/ml, maximum tumor diameter≥ 4 cm, and the absence of postoperative chemotherapy were independent risk factors for the poor prognosis of pancreatic cancer (P<0.05). The discrimination ability, calibration ability, and clinical effectiveness of Nomogram prognostic model were better than those of the TNM staging system. Conclusion The constructed Nomogram prognostic model has higher accuracy and level of discrimination and more clinical benefits than the TNM staging prognostic model.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone