This article summarizes the nursing care of a pediatric patient with melioidosis complicated by septic shock.Key nursing interventions included:to arrange the sequence of drugs reasonably to ensure the safety of the combined use of multiple drugs;systemic anti-infection treatment combined with special treatment of locally infected skin promotes wound healing;in view of the characteristics of the bacteria causing melioidosis,strict isolation and long-term monitoring measures for hospital infection control should be formulated;to enhance the disease coping ability of the child and parents and alleviate negative emotions.After 100 days of intensive treatment and meticulous nursing care,the patient's condition improved,and the discharge was achieved.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To evaluate the effect of exogenous short-chain fatty acids (SCFAs) preconditioning on the expression of zonula occludens-1 (ZO-1) in lung tissues of rats undergoing extracorporeal circulation (ECC).Methods:Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 320-420 g, were divided into sham operation group (S group), ECC group (E group) and SCFAs group, with 12 rats in each group. Seven days before the ECC, short-chain fatty acids dissolved in 2 ml of normal saline was given by gavage daily in SCFAs group, while the equal volume of normal saline was given by gavage in S group and E group. On the 8th day, E group and SCFAs group underwent arteriovenous catheterization and ECC for 1 h, while S group only underwent catheterization without ECC. Lung tissues were collected to observe the pathological results and detect the expression of ZO-1 (by Western blot), and the wet/dry lung weight ratio was calculated.Results:Compared with S group, the wet/dry lung weight ratio was significantly increased ( P<0.05), the expression of ZO-1 protein in lung tissue was down-regulated ( P<0.05), and the pathological damage of lung tissues was aggravated in E group and SCFAs group. Compared with E group, the wet/dry lung weight ratio was significantly decreased, the expression of ZO-1 protein in lung tissues was up-regulated ( P<0.05), and the pathological damage of lung tissues was significantly alleviated in SCFAs group. Conclusions:The mechanism by which SCFAs preconditioning attenuates lung injury may be related to up-regulation of ZO-1 expression in lung tissues of rats undergoing ECC.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To evaluate the effect of exogenous short-chain fatty acids (SCFAs) preconditioning on the expression of zonula occludens-1 (ZO-1) in lung tissues of rats undergoing extracorporeal circulation (ECC).Methods:Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 320-420 g, were divided into sham operation group (S group), ECC group (E group) and SCFAs group, with 12 rats in each group. Seven days before the ECC, short-chain fatty acids dissolved in 2 ml of normal saline was given by gavage daily in SCFAs group, while the equal volume of normal saline was given by gavage in S group and E group. On the 8th day, E group and SCFAs group underwent arteriovenous catheterization and ECC for 1 h, while S group only underwent catheterization without ECC. Lung tissues were collected to observe the pathological results and detect the expression of ZO-1 (by Western blot), and the wet/dry lung weight ratio was calculated.Results:Compared with S group, the wet/dry lung weight ratio was significantly increased ( P<0.05), the expression of ZO-1 protein in lung tissue was down-regulated ( P<0.05), and the pathological damage of lung tissues was aggravated in E group and SCFAs group. Compared with E group, the wet/dry lung weight ratio was significantly decreased, the expression of ZO-1 protein in lung tissues was up-regulated ( P<0.05), and the pathological damage of lung tissues was significantly alleviated in SCFAs group. Conclusions:The mechanism by which SCFAs preconditioning attenuates lung injury may be related to up-regulation of ZO-1 expression in lung tissues of rats undergoing ECC.

This article summarizes the nursing care of a pediatric patient with melioidosis complicated by septic shock.Key nursing interventions included:to arrange the sequence of drugs reasonably to ensure the safety of the combined use of multiple drugs;systemic anti-infection treatment combined with special treatment of locally infected skin promotes wound healing;in view of the characteristics of the bacteria causing melioidosis,strict isolation and long-term monitoring measures for hospital infection control should be formulated;to enhance the disease coping ability of the child and parents and alleviate negative emotions.After 100 days of intensive treatment and meticulous nursing care,the patient's condition improved,and the discharge was achieved.

Objective:To analyze the comprehensive blood inflammation index of the patients with stage I pneumoconiosis complicated with pulmonary infection, and to explore its value in predicting the patients' disease.Methods:In September 2023, 83 patients with stage I pneumoconiosis who were treated in Tianjin Occupational Diseases Precaution and Therapeutic Hospital from November 2021 to August 2023 were selected and divided into non-infected group (56 cases) and infected group (27 cases) according to whether they were combined with lung infection. Workers with a history of dust exposure but diagnosed without pneumoconiosis during the same period were selected as the control group (65 cases) . By referring to medical records and collecting clinical data such as gender, age, occupational history, past medical history, hematology testing, the differences in the comprehensive blood inflammation indexes among the three groups were compared, ROC curve was drawn, and the relationship between comprehensive blood inflammation indexes and stage I pneumoconiosis and its combined lung infection was analyzed.Results:There were significtant differences in the number of neutrophils (N) , the number of lymphocytes (L) , the number of monocytes (M) , C-reactive protein (CRP) , the neutrophil to lymphocyte ratio (NLR) , the monocyte to lymphocyte ratio (MLR) , the platelet to lymphocyte ratio (PLR) , the systemic immune-inflammatory index (SII) , the systemic inflammation response index (SIRI) , the aggregate index of systemic inflammation (AISI) , the derived neutrophil to lymphocyte ratio (dNLR) , the neutrophil to lymphocyte and platelet ratio (NLPR) , and the C-reactive protein to lymphocyte ratio (CLR) ( P<0.05) . Compared with the control group, MLR, SIRI and AISI in the non-infected group were significantly increased ( P<0.05) . NLR, MLR, PLR, SII, SIRI, AISI, dNLR, NLPR, CLR were significantly increased ( P<0.05) . Compared with the non-infected group, NLR, PLR, SII, SIRI, AISI, dNLR, NLPR and CLR were significantly increased in the infected group ( P<0.05) . ROC analysis showed that NLR, MLR, PLR, SII, SIRI and AISI had a certain predictive capability for stage I pneumoconiosis ( P<0.05) , among which MLR had the highest efficacy, with an AUC of 0.791 (95% CI: 0.710-0.873) , the cut-off value was 0.18, the sensitivity was 71.4%, and the specificity was 78.5%. NLR, MLR, PLR, SII, SIRI, AISI, dNLR, NLPR and CLR all had a certain predictive capability forstage I pneumoconiosis combined lung infection ( P<0.05) , among which CLR had the highest efficacy, with an AUC of 0.904 (95% CI: 0.824~0.985) , the cut-off value was 5.33, sensitivity was 77.8%, specificity was 98.2%. Conclusion:The comprehensive blood inflammation index may be an auxiliary predictor of stage I pneumoconiosis and its combined lung infections.

This study was performed to investigate the inhibitory effects of Xuebijing injection(XBJ)on lipopolysaccharide(LPS)-induced inflammatory signals on EA.hy926 vascular endothelial cells and the underlying mechanism,and to provide a theoretical basis for the treatment of sepsis with XBJ.WST-1 assay was used to detect the effects of XBJ on the cell viability;Western blot analysis was performed to detect the protein expression levels of IκBα,p-p65,p-ERK,p-JNK,p-p38,p-AMAD17 in cell lysates and the content of sTLR4 fragment in the concentrated culture supernatants.ADAM17 sheddase activity in cells was detected by using a commercial available kit.Data showed that all of the TLR4-mediated inflammatory signals were significantly inhibited by the treatment of XBJ(P＜0.01).ADAM17 phosphorylation and shedding activity were induced by XBJ treatment,simultaneously the sTLR4 contents in the culture media were increased.XBJ-induced shedding of TLR4 was suppressed by the preteatment of 10 μmol/L TAPI-1(an ADAM17 inhibitor).Taken together,XBJ can induce the shedding of TLR4 from cell membrane by up-regulating ADAM17 shedding activity,thereby inhibiting the activation of TLR4-mediated intracellular inflammatory signals in EA.hy926 cells.

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2^f/fLyz2-Cre^+/- mice. Synovial inflammation and M1 polarization were improved in GRK2^f/fLyz2-Cre^+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1⁺ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.