The αPD-L1 antibody-based immune checkpoint blockade therapy is still limited by the poor clinical response rate as it is mainly utilized to block surface PD-L1 on tumor cells while ignoring abundant PD-L1 exosomes secreted in the environment, causing tumor immune evasion. Here, we proposed an exosome biogenesis inhibition strategy to suppress tumor exosomes secretion from the source, reducing the inhibitory effect on T cells and enhancing chemo-immunotherapy efficacy. We developed sulfafurazole homodimers (SAS) with disulfide linkages, effectively releasing the drug in response to glutathione (GSH) and inhibiting 4T1 tumor-derived exosomes secretion. Subsequently, gemcitabine (Gem) was encapsulated to induce immunogenic cell death (ICD). Consequently, Gem@SAS inhibited the secretion of tumor exosomes by more than 70%, increased proliferation and granzyme B secretion ability of T cells by more than 2 times, and showed superior efficacy in breast cancer treatment as well as lung metastasis of breast cancer.

Background and purpose:Plasmacytoid dendritic cells are one of the key immune cells in the tumor microenvironment(TME),which can directly or indirectly regulate tumor related immune responses and play multiple roles in the development and metastasis of tumors.This study aimed to investigate the correlation between plasmacytoid dendritic cells in lymph nodes and lymph node metastasis in patients with advanced gastric cancer.Methods:Postoperative lymph node tissue specimens and clinicopathological data from advanced gastric cancer patients who underwent D2 radical surgery in the Department of General Surgery at the First Hospital of Dandong were gathered from January 2019 to December 2023.The lymph nodes were grouped based on pTNM staging and the diameter of metastatic lesions.This study was approved by the Medical Ethics Committee of Dandong First Hospital(No.DDSDYYY-LLSC-2025-02-18-019-01),and all patients signed informed consents.Immunohistochemical staining was used to detect the expression levels of CD123-positive plasmacytoid dendritic cells in different lymph node groups,and their correlation with lymph node metastasis in advanced gastric cancer was further analyzed.Results:Of the 116 patients,plasmacytoid dendritic cells infiltrate the lymph node tissues of gastric cancer patients.As tumor differentiation decreased and pT stage,pathological stage,lymphatic/vascular invasion,and perineural invasion increased,the mean number of CD123-positive pDC in metastatic lymph nodes rose significantly(P＜0.05).The number of CD123-positive plasmacytoid dendritic cells was higher in metastatic lymph node-positive tissues than in metastatic lymph node-negative tissues,the number was higher in the macrometastasis group of pN1-3 staging than in the micrometastasis group,and the number was higher in the non-metastatic lymph node group of pN1-3 staging than in the pN0 staging lymph node group(P＜0.05).In lymph node metastasis-positive cases,the number of CD123-positive plasmacytoid dendritic cells was higher in second-station lymph nodes than in first-station lymph nodes(P＜0.05).Conclusion:The infiltration of CD123-positive plasmacytoid dendritic cells in lymph nodes of patients with advanced gastric cancer is closely associated with lymph node metastasis and may serve as a prerequisite for metastatic spread.Understanding the distribution of CD123-positive plasmacytoid dendritic cells in gastric cancer lymph nodes can help further explore their role in the immune microenvironment of gastric cancer.Targeted therapy focusing on CD123-positive plasmacytoid dendritic cells may become a new strategy for the treatment of advanced gastric cancer.

Objective:To construct a data integration platform for oxygen inhalation equipment of suction type,so as to explore its application effect in risk management for the operation of oxygen inhalation equipment of suction type.Methods:The data integration platform for oxygen inhalation equipment of suction type adopted a browser-server(B/S)architecture,with four modules:equipment list,quarterly data confirmation,system settings,and entry for key equipment,which can achieve full-process management for operational risks of oxygen inhalation equipment of suction type.A total of 40 oxygen inhalation equipment of suction type in clinical use of Huashan Hospital of Fudan University from January 2022 to December 2023 were selected.Equipment management from January to December 2022 was set as the pre-application management of the data integration platform of oxygen inhalation equipment of suction type,and the equipment management from January to December 2023 was set as the post-application management of that.The incidence of risk events of equipment,consumed time of emergency management for risk events,standardization scores of equipment management,and control rates for risks of equipment alarm were compared between before and after platform was applied.Results:After the data integration platform was applied,the incidence rates of equipment damage,record loss,and associated infections were respectively 3.85%,4.62%and 6.15%,which were lower than those before it was applied,with statistically significant differences(x2=9.957,11.217,7.386,P<0.05).The consumed times of emergency management for risk events related to safety of equipment power,safety of diagnosis and treatment,biological safety,and radiation safety were respectively(1.02±0.14)h,(1.06±0.15)h,(1.03±0.12)h and(1.15±0.14)h after the data integration platform was applied,all of which were shorter than those before it was applied,with statistically significant differences(t=10.913,9.954,8.917,13.572,P<0.05).The standardization scores of the management for use and operation,disinfection and sterilization,maintenance and upkeep,and fault repair of oxygen inhalation equipment of suction type after the data integration platform was applied were significantly higher than those before it was applied,with statistically significant differences(t=11.787,10.779,10.233,12.561,P<0.05).The average qualification rate of alarm threshold value,and qualification rate of equipment maintenance after the platform was applied were higher than those before it was applied,while the average mute rate of alarm after it was applied was lower than that before it was applied,with statistically significant differences(t=7.064,5.998,15.629,P<0.05).Conclusion:The application of the data integration platform in oxygen inhalation equipment of suction type can improve management capabilities for equipment,and strengthen monitoring and early warning functions for equipment,and reduce operational risks of the equipment after it is applied in the management for oxygen inhalation equipment of suction type.

Objective:To construct a data integration platform for oxygen inhalation equipment of suction type,so as to explore its application effect in risk management for the operation of oxygen inhalation equipment of suction type.Methods:The data integration platform for oxygen inhalation equipment of suction type adopted a browser-server(B/S)architecture,with four modules:equipment list,quarterly data confirmation,system settings,and entry for key equipment,which can achieve full-process management for operational risks of oxygen inhalation equipment of suction type.A total of 40 oxygen inhalation equipment of suction type in clinical use of Huashan Hospital of Fudan University from January 2022 to December 2023 were selected.Equipment management from January to December 2022 was set as the pre-application management of the data integration platform of oxygen inhalation equipment of suction type,and the equipment management from January to December 2023 was set as the post-application management of that.The incidence of risk events of equipment,consumed time of emergency management for risk events,standardization scores of equipment management,and control rates for risks of equipment alarm were compared between before and after platform was applied.Results:After the data integration platform was applied,the incidence rates of equipment damage,record loss,and associated infections were respectively 3.85%,4.62%and 6.15%,which were lower than those before it was applied,with statistically significant differences(x2=9.957,11.217,7.386,P<0.05).The consumed times of emergency management for risk events related to safety of equipment power,safety of diagnosis and treatment,biological safety,and radiation safety were respectively(1.02±0.14)h,(1.06±0.15)h,(1.03±0.12)h and(1.15±0.14)h after the data integration platform was applied,all of which were shorter than those before it was applied,with statistically significant differences(t=10.913,9.954,8.917,13.572,P<0.05).The standardization scores of the management for use and operation,disinfection and sterilization,maintenance and upkeep,and fault repair of oxygen inhalation equipment of suction type after the data integration platform was applied were significantly higher than those before it was applied,with statistically significant differences(t=11.787,10.779,10.233,12.561,P<0.05).The average qualification rate of alarm threshold value,and qualification rate of equipment maintenance after the platform was applied were higher than those before it was applied,while the average mute rate of alarm after it was applied was lower than that before it was applied,with statistically significant differences(t=7.064,5.998,15.629,P<0.05).Conclusion:The application of the data integration platform in oxygen inhalation equipment of suction type can improve management capabilities for equipment,and strengthen monitoring and early warning functions for equipment,and reduce operational risks of the equipment after it is applied in the management for oxygen inhalation equipment of suction type.

Background and purpose:Plasmacytoid dendritic cells are one of the key immune cells in the tumor microenvironment(TME),which can directly or indirectly regulate tumor related immune responses and play multiple roles in the development and metastasis of tumors.This study aimed to investigate the correlation between plasmacytoid dendritic cells in lymph nodes and lymph node metastasis in patients with advanced gastric cancer.Methods:Postoperative lymph node tissue specimens and clinicopathological data from advanced gastric cancer patients who underwent D2 radical surgery in the Department of General Surgery at the First Hospital of Dandong were gathered from January 2019 to December 2023.The lymph nodes were grouped based on pTNM staging and the diameter of metastatic lesions.This study was approved by the Medical Ethics Committee of Dandong First Hospital(No.DDSDYYY-LLSC-2025-02-18-019-01),and all patients signed informed consents.Immunohistochemical staining was used to detect the expression levels of CD123-positive plasmacytoid dendritic cells in different lymph node groups,and their correlation with lymph node metastasis in advanced gastric cancer was further analyzed.Results:Of the 116 patients,plasmacytoid dendritic cells infiltrate the lymph node tissues of gastric cancer patients.As tumor differentiation decreased and pT stage,pathological stage,lymphatic/vascular invasion,and perineural invasion increased,the mean number of CD123-positive pDC in metastatic lymph nodes rose significantly(P＜0.05).The number of CD123-positive plasmacytoid dendritic cells was higher in metastatic lymph node-positive tissues than in metastatic lymph node-negative tissues,the number was higher in the macrometastasis group of pN1-3 staging than in the micrometastasis group,and the number was higher in the non-metastatic lymph node group of pN1-3 staging than in the pN0 staging lymph node group(P＜0.05).In lymph node metastasis-positive cases,the number of CD123-positive plasmacytoid dendritic cells was higher in second-station lymph nodes than in first-station lymph nodes(P＜0.05).Conclusion:The infiltration of CD123-positive plasmacytoid dendritic cells in lymph nodes of patients with advanced gastric cancer is closely associated with lymph node metastasis and may serve as a prerequisite for metastatic spread.Understanding the distribution of CD123-positive plasmacytoid dendritic cells in gastric cancer lymph nodes can help further explore their role in the immune microenvironment of gastric cancer.Targeted therapy focusing on CD123-positive plasmacytoid dendritic cells may become a new strategy for the treatment of advanced gastric cancer.

Objective:To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection.Methods:A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study.Results:The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months.Conclusions:MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Objective To investigate the effects of long-term administration of tacrolimus(also known as FK506)on the pain-related behaviors in mice and to study the underlying mechanism of pain induced by FK506 via measuring the effect of FK506 on the synaptic expression and phosphorylation of alpha-amino-3-hyroxy-5-methyl-4-isoxazolepropionic acid(AMPA)receptor in the spinal cord dorsal horn of mice.Methods 1)A total of 24 mice were evenly and randomly assigned to two groups,a FK506 group and a Saline group.The FK506 group was given daily intraperitoneal injection of FK506 and the Saline group received normal saline.Both groups received injection once a day for 7 days in a row.Some of the mice(n=6 in each group)were monitored for the changes in the paw withdrawal threshold(PWT),the paw withdrawal latency(PWL),and the spontaneous pain behaviors to establish the pain model.The other mice(n=6 in each group)of each group underwent isolation of the dorsal horn when obvious pain symptoms were induced on day 7 of injection.Then,immunoblotting was performed to determine the synaptic expression and phosphorylation levels of GluA1 and GluA2 subunits of AMPA receptors.2)The mice were randomly divided into two groups,FK506+calcineurin(CaN)group and FK506+Saline group(n=6 in each group).After the pain model was constructed,the mice were given intrathecal injection of recombinant CaN(also know as 33 U)or normal saline.Then,60 minutes later,the PWT and the PWL of the mice were measured to investigate the role of CaN in FK506-induced pain.3)Another18 mice were selected.The mice were randomly and evenly assigned to three groups,a control group(receiving intraperitoneal injection of normal saline followed by intrathecal injection of normal saline),FK506+Saline group(receiving intraperitoneal injection of FK506 followed by intrathecal injection of normal saline)and FK506+CaN group(receiving intraperitoneal injection of FK506 followed by intrathecal injection of CaN).Then,60 minutes later,the spinal cords were isolated and subjected to immunoblotting assay to determine the role of CaN in FK506-induced AMPA receptor modification.Results 1)After 7 consecutive days of intraperitoneal injection of FK506,the PWT and PWL of mice dropped significantly,reaching on day 7 as low as 22.3%±0.05%and 66.6%±0.05%of the control group,respectively(P<0.01).The FK506-treated mice displayed evident spontaneous pain behavior,presenting significantly increased licking activities(P<0.01).These results indicated that FK506-induced pain model was successfully established.Immunoblotting assay showed that the total expressions of GluA1 and GluA2 subunits in the spinal dorsal horn of the FK506 group remained unchanged in comparison with those of the Saline group.However,FK506 specifically induced an increase in the synaptic expression of GluA1.In addition,the phosphorylation levels of GluA1 at Ser845 and Ser831 in FK506-treated mice were significantly increased in comparison with those of the control group(P<0.05).2)Compared with those of the mice in the FK506+Saline group,the PWT and the PWL of mice in the FK506+CaN group were significantly increased(P<0.05).3)Compared with those of the FK506+Saline group,the synaptic expression of GluA1 were decreased in FK506+CaN group(P<0.01)and the phosphorylation levels of GluA1 at Ser845 and Ser831 were significantly downregulated(P<0.001).Conclusion The hyper-expression and hyperphosphorylation of GluA1 subunit in the spinal cord dorsal horn resulting from CaN inhibition contributes to the FK506-induced pain syndrome.FK506 induces the synaptic hyper-expression and hyperphosphorylation of GluA1 in the dorsal horn of the spinal cord through CaN inhibition,thereby inducing pain.

Fibrosis is one of the key factors that lead to the immune exclusion of solid tumors. Although degradation of fiber is a promising strategy, its application was still bottlenecked by the side effects of causing metastasis, resulting in the failure of immunotherapy. Here, we developed an antimetastatic polymer (HPA) for the delivery of chemo-drug and antifibrotic siPAI-1 to form the nano-permeator. Nano-permeator shrank after protonation and deeply penetrated into the tumor core to down-regulate the expression of PAI-1 for antifibrosis, and further promoted the sustained infiltration and activation of T cells for killing tumor cells. Moreover, metastasis after fiber elimination was prevented by multivalent CXCR4 antagonistic HPA to reduce the attraction of CXCL12 secreted by distant organs. The administration of stroma-alleviated immunotherapy increased the infiltration of CD8⁺ T cells to 52.5% in tumor tissues, inhibiting nearly 90% metastasis by HPA in distant organs. The nano-permeator reveals the mechanism and correlation between antifibrosis and antimetastasis and was believed to be the optimizing immunotherapy for solid fibrotic tumors.

Objective:To evaluate the clinical performance of direct antimicrobial susceptibility test in blood culture-positive broth, and to provide a basis for optimizing the antibiotic use strategy in clinical bloodstream infection.Methods:A retrospective analysis was conducted on 780 blood culture-positive samples collected in Peking University People′s Hospital from May 2017 to December 2021. The direct antimicrobial susceptibility test was performed by disk diffusion method on blood culture-positive broth. The antimicrobial susceptibility breakpoints were in accordance with Clinical and Laboratory Standards Institute (CLSI) M100 S32 edition document.Results:In this study, a total of 331 strains of Gram-negative bacteria (139 strains of Escherichia coli, 79 strains of Klebsiella pneumoniae, 35 strains of Pseudomonas aeruginosa, 21 strains of Acinetobacter baumannii) and 396 strains of Gram-positive cocci (25 strains of Staphylococcus aureus, 316 strains of coagulase-negative staphylococci, 47 strains of Enterococcussp.) were collected, after excluding 53 cases with two or more isolates. Compared with the routine antimicrobial susceptibility test (AST), the rates of category agreement (CA), major error (ME), and very major error (VME) of Gram-negative bacteria were 86.0% (1368/1 591), 8.7% (139/1 591), and 0.5% (8/1 591), respectively. On the other hand, the CA%, ME%, and VME% of Gram-positive cocci were 89.2% (960/1 076), 7.5% (81/1 076), and 1% (11/1 076), respectively. Regarding the individual antimicrobial agents, the CA% of Escherichia coli was 16/17 for imipenem, 90.1% (109/121) for meropenem, and 70.8% (85/120) for cefepime. For Klebsiella pneumoniae, the CA% of was 10/13 for imipenem, 80.9% (55/68) for meropenem, and 80.3% (53/66) for cefepime. The CA% of meropenem in Pseudomonas aeruginosa and Acinetobacter baumannii were 96.0% (24/25) and 16/16. The CA% of linezolid and cefoxitin in Staphylococcus aureus were 100% (25/25) and 100% (24/24), respectively. The CA% of linezolid, cefoxitin and gentamicin in coagulase-negative staphylococci were 98.9% (269/272), 94.5% (277/293) and 71.6% (194/271) respectively. Finally, for Enterococcus sp., the CA% of vancomycin and ampicillin were 91.5% (43/47) and 94.7% (36/38), respectively. Conclusion:Compared with the conventional AST, the blood culture-positive broth direct AST exhibited high category agreement and low error rates for both Gram-negative bacteria and Gram-positive cocci, which can serve a rapid alternative for AST in cases of clinical bloodstream infection.

Objective:The aim of this study was to determine the colonization rate of carbapenem-resistant Enterobacterales (CRE) and identify the proportion and risk factors for bloodstream infection.Methods:This was a retrospective study conducted at the Department of Clinical Laboratory, Peking University People′s Hospital from January 2018 to December 2021. A total of 4 993 patients underwent rectal swab CRE screening for CRE, of which 137 were found to be positive. Clinical and laboratory data of the positive patients were collected, and the following parameters were analyzed: the positive rate of CRE screening in high-risk population, the species of colonized bacteria, antimicrobial resistance and the risk factors of CRE bloodstream infection in colonized patients. Statistical analysis was performed using SPSS 26.0 software. Univariate analysis was conducted using the chi-square (χ 2) test, while multivariate analysis was performed using binary logistic regression. The results were expressed as relative risk (odds ratio, OR) and 95% confidence interval ( CI). A significance level of 0.05 was considered statistically significant. The drug resistance rate of pathogen was analyzed by WHONET 5.6 software. Results:During the study period, a total of 4 991 patients who underwent rectal swab screening were eligible for inclusion, of which 137 patients were screened positive, resulting in a positive rate of 2.7% (137/4 991). The positive rates were higher in the intensive care ward and hematology ward, with rates of 5.5% (27/493) and 3.3% (109/3 321), respectively. A total of 145 colonization strains were isolated from patients with positive CRE screening, including 63 strains of Klebsiella pneumoniae (43.4%, 63/145), 52 strains of Escherichia coli (35.9%, 52/145), 16 strains of Enterobacter cloacae (11.0%, 16/145) and 14 strains of other Enterobacterales (9.7%, 14/145). The metal β-lactamase production type was the main component of CRE positive colonizing bacteria. The antimicrobial resistance of 145 strains to 22 antibacterial agents revealed that amikacin and tigacycline were the most sensitive. Among 137 CRE screening-positive patients, 14 (10.2%, 14/137) developed bloodstream infection. The isolated pathogenic bacteria included 10 Klebsiella pneumoniae strains and 4 Escherichia coli strains, with a predominant serine carbapenemase producing. Notably, the enzyme type and antimicrobial resistance of the bloodstream infection isolates in the same patient were highly consistent with those of the previous screening strains. Comparison was made between patients with positive CRE screening and those with CRE conversion to bloodstream infection. The unifactor analysis revealed significant differences in surgical history, neutropenia, hematopoietic stem cell transplantation, history of antibiotic use before rectal swab screening, screening within 48 hours after admission, and serine carbapenemase production by strains ( P<0.05). The multivariate analysis indicated that surgical history ( OR 24.659, 95% CI 2.540-239.411, P=0.006) and neutropenia ( OR 93.796, 95% CI 6.294-1 397.804, P=0.001) remained significantly associated with the risk of CRE bloodstream infection ( P<0.05). Conclusions:The CRE colonization rate was low in our hospital, but the proportion of patients with positive screening converted to bloodstream infection was high. Surgical history and neutropenia are risk factors for bloodstream infection transmission. Thus, it is essential to enhance monitoring in high-risk areas and susceptible patients.