Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

The deficiency in immunogenicity and the presence of immunosuppression within the tumor microenvironment significantly hindered the efficacy of immunotherapy. Consequently, a nanoformulation containing metal sulfide of FeS and GSDMD plasmid (NP_FeS/GD) had been developed to effectively augment antitumor immune responses through dual activation of immunogenic PANoptosis and ferroptosis, as well as reprogramming immunosuppressive effects via H₂S amplification. The bioactive NP_FeS/GD exhibited controlled release of GSDMD plasmid, H₂S, and Fe²⁺ in response to the tumor microenvironment. Fe²⁺, H₂S, and the expression of GSDMD protein could effectively elicit highly immunogenic PANoptosis and ferroptosis. Furthermore, releasing H₂S could mitigate the overexpression of indoleamine 2,3-dioxygenase1 (IDO1) induced by immunogenic PANoptotic and ferroptotic cell death and disrupt the activity of IDO1. Consequently, NP_FeS/GD effectively triggered the antitumor innate and adaptive immune responses through induction of PANoptotic and ferroptotic cell death and reshaped the tumor immunosuppressive microenvironment to enhance antitumor immunotherapy for metastasis inhibition. This study unveiled the significant potential of immunogenic PANoptosis and ferroptosis in H₂S gas therapy for enhancing tumor immunotherapy, offering novel insights and ideas for the rational design of nanomedicine to enhance tumor immunogenicity while reprogramming the tumor immunosuppressive microenvironment.

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.

ObjectiveTo establish a modified BISAP scoring system， and to investigate the value of the BISAP scoring system versus the modified BISAP scoring system in assessing the severity and condition of acute pancreatitis （AP）. MethodsFor the establishment of the new scoring system， a retrospective analysis was performed for the clinical data of 1 033 patients with AP who were admitted to Third Xiangya hospital of central South University from January 2019 to December 2021， and according to the revised Atlanta classification， they were divided into mild acute pancreatitis （MAP） group with 827 patients and severe acute pancreatitis （SAP） group with 206 patients. The two groups were compared in terms of clinical features， laboratory markers， and imaging data. A binary logistic regression analysis was performed for the statistically significant indicators to screen for the independent risk factors for SAP. The receiver operating characteristic （ROC） curve was used to obtain the optimal cut－off value corresponding to the maximum Youden index for each independent risk factor， and a score of 0 or 1 was assigned depending on different situations， which was integrated into the BISAP scoring system to establish a modified BISAP scoring system. For the validation of the new scoring system， a retrospective analysis was performed for the clinical data of 473 patients with AP who were admitted to Third Xiangya hospital of central South University from January 2017 to December 2018. BISAP score and modified BISAP score were determined for each patient， and the area under the ROC curve （AUC） was used to compare the value of the two scoring systems in predicting the severity and prognosis of AP. The chi－square test or the Fisher’s exact test was used for comparison of categorical data between two groups， and the independent－samples t test and the Mann－Whitney U test were used for comparison of continuous data between two groups. ResultsFor the establishment of the new scoring system， there were significant differences between the MAP group and the SAP group in mode of admission， length of hospital stay， ICU admission rate， number of deaths， underlying diseases， and incidence rate of complications （all P<0.05）. The binary logistic regression analysis showed that body temperature， neutrophil－to－lymphocyte ratio （NLR）， C－reactive protein （CRP）， albumin， triglycerides， D－dimer， fibrinogen， and MCTSI score were independent risk factors for SAP （all P<0.05）. The ROC curve analysis showed that CRP （AUC=0.921）， NLR （AUC=0.798）， D－dimer （AUC=0.768）， and MCTSI score （AUC=0.931） had a good predictive value for SAP， and the combination of these four indicators had an AUC of 0.976 and showed a significantly higher diagnostic efficiency than each indicator alone or the combination of two or three indicators （all P<0.05）. For the validation of the new scoring system， a total of 473 patients were enrolled， with 408 in the MAP group and 65 in the SAP group， and there were significant differences between the two groups in mode of admission， length of hospital stay， ICU admission rate， number of deaths， and incidence rate of complications （all P<0.05）. The modified BISAP score was better than the BISAP score in predicting SAP （AUC： 0.972 vs 0.887， P<0.05）， with an optimal cut－off value of >3 points. The modified BISAP score also had a relatively high value in predicting the mortality of AP patients （AUC=0.910）， but there was no significant difference between the modified BISAP score and the BISAP scoring system （AUC： 0.910 vs 0.896， P=0.707）. ConclusionThe modified BISAP score is better than the BISAP score in predicting the severity of AP and has a relatively high value in predicting the mortality of AP patients， giving a more accurate， objective， and early assessment of the condition of AP patients.

Purpose: This retrospective study aimed to re-evaluate the effect of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). Materials and Methods: A total of 498 patients who received neoadjuvant chemotherapy (NCT) combined with concurrent chemoradiotherapy (CCRT) or IMRT were retrospectively reviewed. The distribution of baseline characteristics was balanced using propensity score matching. Additionally, the results of NCT+IMRT and NCT+CCRT were compared using Kaplan-Meier survival analysis, and differences in survival rates were analyzed using the log rank test. Results: There were no significant differences in overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and local progression-free survival (LRFS) between the two groups. Patients were further categorized into risk subgroups based on pretreatment Epstein-Barr virus (EBV) DNA cutoff values using receiver operating characteristic curve analysis. There were no statistically significant differences in OS, PFS, DMFS, and LRFS between patients who received NCT+CCRT and NCT+IMRT in the high-risk group. In the low-risk group, although there were no differences between NCT+CCRT and NCT+IMRT in OS, PFS, and LRFS, patients who received NCT+CCRT had better DMFS than those who received NCT+IMRT. Conclusion Pretreatment EBV DNA level can be used to individualize concurrent chemotherapy for patients with locally advanced NPC. Patients with low pretreatment EBV DNA levels may benefit from concurrent chemotherapy, whereas those with high levels may not. Other treatment modalities need to be explored for high-risk patients to improve their prognosis.

Background Programmed necrosis is closely related to the occurrence and development of neurodegenerative diseases, but whether lead causes programmed cell necrosis has not been reported. Objective This experiment is designed to probe into the function of programmed necrosis and the effect of its inhibitor on lead-induced microglia (BV2 cell) injury. Methods The BV2 cells at logarithmic growth phase were treated with 0, 1, 5, 10, 25, 50, 100, and 200 μmol·L⁻¹ lead acetate for 12, 24, 36, and 48 h, respectively, and methylthiazolyldiphenyl-tetrazolium bromide (MTT) was used to determine cell viability. After treatment with 0, 25, 50, and 100 μmol·L⁻¹ lead acetate for 24 h, enzyme-linked immunosorbent assay, Western blotting, and flow cytometry were used to determine the expressions of tumor necrosis factor-α (TNF-α), receptor-interacting protein kinase 3 (RIPK3), receptor-interacting protein kinase 1 (RIPK1), and mixed lineage kinase domain-like protein (MLKL) in the cells, and the effect of RIPK1 inhibitor Nec-1 pretreatment on lead-induced BV2 cell injury . Results The BV2 cell viability decreased with higher lead concentration (r_{12 h}=−0.995, r_{24 h}=−0.984, r_{36 h}=−0.983, r_{48 h}=−0.981, all P<0.01) and time extension (only for 5 μmol·L⁻¹ lead acetate, r=−0.994, P<0.01). Compared with the control group, the BV2 cell viability decreased at the same exposure time when the concentration of lead was above 10 μmol·L⁻¹ (P<0.01). Compared with the control group, the expressions of RIPK1 and MLKL were increased in the 25, 50, and 100 μmol·L⁻¹ lead groups (P<0.05 or 0.01), accompanied by an increase in the contents of inflammatory cytokine TNF-α, especially in the 100 μmol·L⁻¹ lead group, the increment was the highest (P<0.01). The expression levels of p-RIPK1 and p-MLKL in BV2 cells were both increased when the concentration of lead acetate was above 50 μmol·L⁻¹ (P<0.01). In addition, pretreatment with Nec-1 increased the cell viability rate and decreased the necrosis and late apoptosis rate of BV2 cells exposed to lead compared with corresponding lead exposure groups (P<0.05). Conclusions Lead can reduce BV2 cell viability, increase necrosis rate, and up-regulate the expressions of RIPK1, RIPK3, amd MLKL, and the phosphorylation levels of RIPK1 and MLKL. The RIPK1 inhibitor Nec-1 has an intervention effect on lead-induced damage in BV2 cells, indicating that programmed necrosis may play a role in lead neurotoxicity.

Tumor microenvironment has been widely utilized for advanced drug delivery in recent years, among which hypoxia-responsive drug delivery systems have become the research hotspot. Although hypoxia-responsive micelles or polymersomes have been successfully developed, a type of hypoxia-degradable nanogel has rarely been reported and the advantages of hypoxia-degradable nanogel over other kinds of degradable nanogels in tumor drug delivery remain unclear. Herein, we reported the synthesis of a novel hypoxia-responsive crosslinker and the fabrication of a hypoxia-degradable zwitterionic poly(phosphorylcholine)-based (

With the spread of novel coronavirus pneumonia (NCP) in December 2019, the management and rehabilitation of elderly patients with hip fractures and protection of medical staff face new challenges, and need to be adjusted appropriately under this very circumstances. Hip fractures in the elderly account for more than half of osteoporotic fractures. Expert group formulate this consensus so as to make better decision against this epidemic and protect patients' families and medical staff. This consensus elaborates not only epidemic condition of NCP, but also general principles of medical admission, treatment and protection for both medical staff and patients, in order to provide some reference and promote the standardization of clinical diagnosis and treatment of elderly patients with hip fractures under the condition of NCP.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

Alkali-salinity exerts severe osmotic, ionic, and high-pH stresses to plants. To under-stand the alkali-salinity responsive mechanisms underlying photosynthetic modulation and reactive oxygen species (ROS) homeostasis, physiological and diverse quantitative proteomics analyses of alkaligrass (Puccinellia tenuiflora) under Na2CO3 stress were conducted. In addition, Western blot,real-time PCR, and transgenic techniques were applied to validate the proteomic results and test the functions of the Na2CO3-responsive proteins. A total of 104 and 102 Na2CO3-responsive proteins were identified in leaves and chloroplasts, respectively. In addition, 84 Na2CO3-responsive phospho-proteins were identified, including 56 new phosphorylation sites in 56 phosphoproteins from chloro-plasts, which are crucial for the regulation of photosynthesis, ion transport, signal transduction, and energy homeostasis. A full-length PtFBA encoding an alkaligrass chloroplastic fructose-bisphosphate aldolase (FBA) was overexpressed in wild-type cells of cyanobacterium Synechocystis sp. Strain PCC 6803, leading to enhanced Na2CO3 tolerance. All these results indicate that thermal dissipation, state transition, cyclic electron transport, photorespiration, repair of pho-tosystem (PS) Ⅱ, PSI activity, and ROS homeostasis were altered in response to Na2CO3 stress, which help to improve our understanding of the Na2CO3-responsive mechanisms in halophytes.