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.

Purpose To investigate the value of T2WI MR-based radiomics nomogram for predicting deep stromal invasion of cervical cancer preoperatively.Materials and Methods Retrospective analysis of 164 consecutive patients with early-stage cervical cancer with postoperative pathological findings and preoperative MR images admitted to two medical centers in the Affiliated Hospital of Southwest Medical University(first center)and the Huaihe Hospital of Henan University(second center)from May 2018 to August 2022.The data in the first center(n=1 14)and the second center(n=50)were divided into the training and validation cohorts,respectively.To segment T2WI images in the 3D Slicer software and to extract image features in the python software.The radiomic features were selected in the training cohort.Based on the selected features,support vector machine prediction model was constructed.Univariate Logistic regression was used to select clinicopathological risk factors,then,multi-variate Logistic regression combined with radiomics score was used to construct radiomics nomogram,diagnostic performance of the radiomics model,clinical prediction model and radiomics nomogram model were assessed by receiver operating characteristic analysis.The predictive efficacy of the different models were compared.Results The 12 radiomics features were selected out.The FIGO staging and radiomics score were included in the multifactor Logistic regression to build the radiomics nomogram for predicting deep stromal invasion.The results showed that the predictive performance for the radiomics nomogram model was better than the clinical prediction model(in validation cohort:area under the curve was 0.845 vs.0.717;Z=2.728,P=0.006).Conclusion Radiomics nomogram based on T2WI is of high value for predicting deep stromal invasion of cervical cancer preoperatively.

Neuropathic pain (NP) is a common complication following spinal cord injury, with an incidence rate ranging from 38% to 70%. NP typically presents as sensation of burning, electric shocks, tingling or squeezing pain resulting from somatosensory nerve damage, which exerts a negative impact on patients′ physical and psychological well-being. After spinal cord injury, glial cells are activated to induce inflammatory cascade. Accordingly, various inflammatory mediators that may disrupt the neuronal function are released to promote abnormally increased neuronal excitability and pain signal transduction. Additionally, spinal cord injury can disrupt the release of neurotransmitters and neurotrophic factors, alter ion channel activity, and thereby impair the normal pain regulatory mechanisms and further increase pain perception. The interaction of these mechanisms contributes to the occurrence and persistence of NP after spinal cord injury. However, the precise pathogenesis of NP remains incompletely elucidated, making its therapeutic efficacy uncertain and clinical management difficult. It is of great significance to thoroughly understand the underlying pathophysiological mechanisms of NP following spinal cord injury for its treatment. For this reason, the authors reviewed the research progress on the characteristics and pathophysiological mechanisms of NP following spinal cord injury, aiming to serve as a reference for further research and development of more effective targeted therapies and management strategies.

Objective To investigate the expression of ALKBH3-AS1 in peripheral blood CD4+T cells of patients with systemic lupus erythematosus(SLE)and its correlation with T helper cell 17/regulatory T cells(Th17/Treg)and disease activity.Methods A total of 60 patients diagnosed with SLE in Leshan Hospital of Traditional Chinese Medicine from July 2020 to March 2024 were retrospectively collected.According to SLEDAI score,they were divided into active group(n=33,SLEDAI ≥ 10 score)and stable group(n=27,SLEDAI＜10 score).At the same time,52 healthy subjects were selected as control group.The general data of three groups were collected and peripheral blood mononuclear cell(PBMC)was obtained by centrifugation in peripheral blood.CD4+T cells were isolated by immunomagnetic beads,and Th17/Treg ratio was detected by flow cytometry.The relative expression levels of ALKBH3-AS1 and retinoid-related orphan receptor γ t(ROR γ t)in CD4+T cells were detected by fluorescence quantitative PCR.The contents of transforming growth factor(TGF)-β and interleukin(IL)-17 in serum were determined by enzyme-linked immunosorbent assay(ELISA).The levels of C3 and C4 were determined by rate scattering immunoturbidimetry.Pearson analyzed the correlation between ALKBH3-AS1,Th17 and various clinical indicators in SLE patients.Logistic regression analysis of the influencing factors in patients with severe SLE showed that the difference was statistically significant.Results Hb,ALB,ALKBH3-AS1 mRNA,CD4+T,complement C3 and C4 in the control group were significantly higher than those in SLE group(t/Z=3.245,-11.169,-12.675,-17.829,-15.240,-19.212),RDW,TGF-β,RORγ t,Th17/Treg,IL-17,and CRP in the control group were lower than that in SLE group(t/Z=4.206,10.054,19.869,37.942,50.463,3.115),and the differences were statistically significant(all P＜0.05).ALB,ALKBH3-AS1 mRNA,CD4+T in the active group were significantly lower than those in the stable group(t/Z=-8.918,-2.483,-11.694),CRP,TGF-β,RORγt,Th17/Treg,and IL-17 were significantly higher than those in the stable group(t/Z=3.121,5.671,1.787,14.720,12.044),and the differences were statistically significant(all P＜0.05).Pearson analysis showed that ALKBH3-AS1 was positively correlated with CD4+T(r=0.663),and negatively correlated with Th17/Treg,IL-17,TGF-β,ROR γ t,SLED AIindex(r=-0.687,-0.715,-0.705,-0.678,-0.671),Th17/Treg was negatively correlated with CD4+T(r=-0.817),and positively correlated with IL-17,TGF-β,ROR γ t,SLED AI index with statistical significance(r=0.687,0.767,0.598,0.704).Logistics regression analysis,showed that increased CD4+T[OR(95％CI):0.715(0.304～0.904)]proportion and up-regulated ALKBH3-AS1[OR(95％CI):0.654(0.320～0.987)]expression were protective factors affecting disease activity in SLE patients.The contents of TGF-β[OR(95％CI):1.487(1.120～1.814)]and IL-17[OR(95％CI):1.294(1.217～1.887)]were up-regulated,the proportion of Th17/Treg[OR(95％)CI:1.674(1.361～1.679)]was up-regulated,and the relative expression of ROR γ t[OR(95％)CI:1.547(1.252～1.941)]was increased as risk factors affecting disease activity in SLE patients.Conclusion The down-regulated expression of ALKBH3-AS1 and up-regulated expression of TGF-β,ROR γ t and IL-17 in CD4+T cells of SLE patients are all correlated with disease activity,and can be potential biomarkers for diagnosis,disease activity and efficacy evaluation in SLE patients.

BACKGROUND:Extracellular vesicles can regulate insulin resistance and control inflammatory response by participating in intercellular communication,while repairing skeletal muscles and promoting skeletal muscle regeneration,which is expected to be a novel treatment modality for sarcopenic obesity. OBJECTIVE:To review the biogenesis of extracellular vesicles,their biological functions,their relationship with sarcopenic obesity,and recent advances in the pathogenesis,diagnosis,and treatment of sarcopenic obesity. METHODS:The first author performed a computer search of PubMed,Embase,CNKI and other databases for relevant studies involving extracellular vesicle in sarcopenic obesity.The search keywords were"extracellular vesicle,exosome,sarcopenic obesity,obese sarcopenia,skeletal muscle regeneration,skeletal muscle mass regulation"in English and Chinese,respectively.The search period was from June 2022 to November 2022.After screening,87 articles were included for further review. RESULTS AND CONCLUSION:Extracellular vesicles are important vectors of bidirectional cell communication and participate in the regulation of normal physiological and pathological processes through autocrine,paracrine and endocrine ways.Sarcopenic obesity is a complex multi-factor disease.Extracellular vesicles are involved in the occurrence and development of sarcopenic obesity mainly by regulating the inflammatory response of skeletal muscle and the homeostasis of muscle cells.Cytokines secreted by adipose tissue and skeletal muscle are released into the extracellular circulation through extracellular vesicle encapsulation and interact with each other to promote skeletal muscle insulin resistance and lipogenesis,which is the main pathophysiology of skeletal muscle atrophy in sarcopenic obesity.Extracellular vesicles not only promote the development of sarcopenic obesity by providing specific pathogenic markers,but also are a valuable diagnostic indicator of sarcopenic obesity.Release of extracellular vesicles from skeletal muscle during exercise enhances metabolic response and promotes skeletal muscle regeneration.Extracellular vesicles can not only be used as therapeutic targets for sarcopenic obesity but also be used to treat sarcopenic obesity by loading drugs to effectively improve drug bioavailability.

Objective To investigate the chemical composition from the flowers of Callerya speciosa,and reveal the metabolites difference at different flowering periods based on metabolomics technology.Methods The primary and secondary metabolites,volatile chemical components in flowers of C.speciosa were analyzed combined by GC-MS and UPLC-Q-Exactive MS.Principal component analysis(PCA),orthogonal partial least squares-discriminant analysis(OPLS-DA),and hierarchical cluster analysis(HCA)were performed to identify differential metabolites.Results A total of 332 compounds were identified by UPLC-Q-Exactive MS,mainly including secondary metabolites such as flavonoids,triterpenoids,phenylpropanoids.A total of 297 compounds were identified by GC-MS,mainly including primary metabolites and volatile chemical components,such as organic acids,amino acids,saccharides,heterocycles,alcohols.The PCA analysis demonstrated that the metabolites of the four flowering periods were divided into two groups:bud,initial bloom and blooming periods clustered into one group,while wilting period clustered into the other group,the main differences were filtered and identified as flavonoids and triterpenoids,organic acids,respectively.Compared to the upright type,the flowers of vine type contained more characteristic flavonoids as differential metabolites during the bud,initial bloom and blooming periods,and some flavonoids decrease gradually with the development of flowering.Conclusion The results indicated that the flowers of C.speciosa possessed abundant active flavonoid metabolites for further utilization,and the best harvest stage is initial bloom,the best harvest plant is vine type.This study provides a scientific basis for the scientific development and rational use of the flowers of C.speciosa.

Osteoporosis seriously threatens the living quality of people, especially the elderly, and causes a huge economic burden to society. In the past, bisphosphonates, denosumab and other first-line drugs were used in the treatment of osteoporosis. However, these drugs can only inhibit bone resorption, but can not promote bone formation. Studies have shown that mesenchymal stem cells (MSCs) can be used to treat osteoporosis, however, it has some defects and deficiencies, such as genetic instability, limited cell survival and increased risk of cancer. However, mesenchymal stem cell-derived exosomes (MSCs-Exos) can regulate the differentiation and proliferation of osteoblasts by mediating wingless and int-1 (Wnt)/β-catenin and mitogen-activated protein kinase (MAPK) signaling pathways, promote bone regeneration, and thus has an impact on osteoporosis. In this paper, preclinical studies on MSCs and MSCs-Exos in the treatment of osteoporosis in recent years were reviewed, in order to provide a new idea for the treatment of osteoporosis.

OBJECTIVE: To investigate the effect of β-arrestin1 overexpression on tumor progression in a NCG mouse model bearing T-cell acute lymphocytic leukemia (T-ALL) Molt-4 cell xenograft. METHODS: Molt-4 cells were tagged with firefly-luciferase (F-Luc) by lentiviral infection, and fluorescence intensity of the cells was detected using a luminescence detector. Molt-4 cell lines with β-arrestin1 overexpression or knockdown were constructed by lentivirus infection and injected the tail vein in sub-lethal irradiated NCG mice. Body weight changes and survival time of the xenografted mice were observed, and the progression of T-ALL in the mice was evaluated using an fluorescence imaging system. Sixteen days after xenografting, the mice were euthanatized and tumor cell infiltration was observed in the slices of the liver and spleen. RESULTS: We successfully tagged Molt-4 cells with F-Luc and overexpressed or knocked down β-arrestin1 in the tagged cells. Bioluminescent imaging showed obvious luminescence catalyzed by F-Luc in Molt-4 cells. After injection of Molt-4-Luc cells into irradiated NCG mice, a gradual enhancement of luminescence in the xenografted mice was observed over time, while the body weight of the mice decreased. Compared with the control mice, the mice xenografted with β-arrestin1-overexpressing Molt-4 cells had significantly prolonged survival time ( < 0.001), while the survival time of the mice xenografted with Molt-4 cells with β- arrestin1 knockdown was significantly shortened ( < 0.001). Histological examination revealed fewer infiltrating tumor cells in the liver and spleen of the mice xenografted with β-arrestin1-overexpressing Molt-4 cells in comparison with the mice bearing parental Molt-4 cell xenografts. CONCLUSIONS β-arrestin1 overexpression suppresses tumor progression in mice bearing Molt-4 cell xenograft.
Animals ; Disease Progression ; Heterografts ; Humans ; Mice ; T-Lymphocytes ; Transplantation, Heterologous ; beta-Arrestin 1

Objective To understand colonization of pathogens in nasal vestibular of health care workers (HCWs) in intensive care unit (ICU),and provide evidence for strengthening the prevention and control of healthcare-associated infection (HAI)in ICU.Methods On may 2015,colonization status of pathogens in nasal vestibular of uninfected HCWs in ICU were actively screened,bacterial culture,isolation and identification were performed.The surveyed results were analyzed and compared with antimicrobial resistance of pathogens from patients at the same stage.Results A total of 96 HCWs were surveyed,43 pathogenic strains were isolated from different HCWs’na-sal vestibular,isolation rate and carriage rate were both 44.79%.The main pathogenic bacteria was Staphylococcus aureus(n=15,34.88%),followed by Enterobacter aerogenes (n =9,20.93%)and Klebsiella pneumoniae (K . pneumoniae ,n=7,16.28%).There was a high detection rate of pathogens from nasal vestibular of doctors,HCWs who smoked frequently and those who never exercised (all P <0.05).There were 1 strain of imipenem-resistant K . pneumoniae among 43 pathogenic strains.Resistance rate of 7 K .pneumoniae from HCWs to ampicillin/sulbactam, cefazolin,and furantoin were all >50.00%,resistance rates to cefotaxime and imipenem were 28.57% and 14.29%respectively;resistance rates of 11 strains of K .pneumoniae from patients to furantoin was 100.00% during the same stage,but were sensitive to other commonly used antimicrobial agents.Resistance rate of 4 strains of Esche-richia coli (E.coli)to ampicillin was 75.00%,to gentamicin,tobramycin,levofloxacin,ciprofloxacin,and com-pound sulfamethoxazole were all 50.00%,6 strains of E.coli isolated from patients during the same period were found to be resistant to most commonly used antimicrobial agents.Conclusion Colonization rate of pathogens is high in nasal vestibular of HCWs in ICU,active screening and monitoring on colonization of pathogens in HCWs’ nasal vestibular is significant for preventing the occurrence and cross transmission of HAI among HCWs and pa-tients.

Objective To understand the specimen sources,clinical characteristics,and antimicrobial resistance of Burkholderia cepacia (B .cepacia )isolated from infected patients in intensive care unit(ICU),so as to provide reference for guiding rational use of antimicrobial agents.Methods Clinical data of patients with B .cepacia infec-tion in an ICU between 2011 and 2014 were analyzed retrospectively,antimicrobial resistance of strains was ana-lyzed.Results A total of 267 B .cepacia strains were isolated,the major specimen sources were sputum (80.15%, n=214),blood(14.23%,n =38),and urine(3.37%,n =9).Antimicrobial susceptibility testing results revealed that B .cepacia had multiple resistance,and was naturally resistant to multiple clinically used antimicrobial agents, such as ampicillin,cefazolin,ampicillin/sulbactam,nitrofurantoin,and cefuroxime,resistant rates were all 100%;resistant rates to ceftazidime and levofloxacin were 4.12% and 3.00% respectively;resistant rate to compound sulfa-methoxazole had increased tendency(χ2 =5.885,P =0.015).Conclusion Isolation of B .cepacia in ICU increased year by year,antimicrobial resistance is serious,management and targeted monitoring of prevention and control of healthcare-associated infection should be strengthened,antimicrobial agents should be chosen according to antimi-crobial susceptibility testing results.