ABSTRACT
Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in-depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT-PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA-induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti-lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine-mediated anti-tumor therapy.
Subject(s)
Artemisinins , Lung Neoplasms , Mitochondria , Mitochondrial Precursor Protein Import Complex Proteins , Pyroptosis , Lung Neoplasms/drug therapy , Artemisinins/pharmacology , Humans , Mitochondria/drug effects , Mitochondria/metabolism , Pyroptosis/drug effects , Mice , Animals , Cell Line, Tumor , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , DNA, Mitochondrial , A549 Cells , Signal Transduction/drug effects , Mice, Inbred BALB CABSTRACT
In our previous study, target drug delivery and treatment of malignant tumors have been achieved by using platelets as carriers loading nano-chemotherapeutic agents (ND-DOX). However, drug release from ND-DOX-loaded platelets is dependent on negative platelet activation by tumor cells, whose activation is not significant enough for the resulting drug release to take an effective anti-tumor effect. Exploring strategies to proactively manipulate the controlled release of drug-laden platelets is imperative. The present study innovatively revealed that photodynamic action can activate platelets in a spatiotemporally controlled manner. Consequently, based on the previous study, platelets were used to load iron oxide-polyglycerol-doxorubicin-chlorin e6 composites (IO-PG-DOX-Ce6), wherein the laser-triggered drug release ability and anti-tumor capability were demonstrated. The findings suggested that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability. Importantly and interestingly, drug-loaded platelets were significantly activated by laser irradiation, characterized by intracellular ROS accumulation and up-regulation of CD62p. Additionally, scanning electron microscopy (SEM) and hydrated particle size results also showed a significant aggregation response of laser irradiated-drug-loaded platelets. Further transmission electron microscopy (TEM) measurements indicated that the activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells. Finally, the co-culture model of drug-loaded platelets and tumor cells proved that laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells. Overall, the present study discovers a drug-loaded platelets delivery using photodynamic effect, enabling laser-controlled intelligent drug delivery and anti-tumor therapy, which provides a novel and feasible approach for clinical application of cytopharmaceuticals.
What is the context?1. Platelets were applied to load IO-PG-DOX-Ce6, wherein the laser-triggered drug release and anti-tumor effect were investigated in vitro.2. The findings indicated that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability, which may attribute to the activation of autophagy in platelets.3. IO-PG-DOX-Ce6-loaded platelets could be significantly activated by laser irradiation (690 nm).4. Activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells5. The co-culture model of drug-loaded platelets and tumor cells proved that the laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells.What is new?1. Platelets could be utilized as the vehicle to load photosensitizer-loaded-nano-drug.2. Photodynamic action can activate platelets in a spatiotemporally controlled manner, which could be a tool to regulate the activation of platelets.3. The laser-triggered activation of drug-loaded platelets allows for target release of cargo.4. The limitation of the current research is that only in vitro experiments were carried out to demonstrate our conclusions.What is impact?The present work provides a novel and feasible approach for the clinical application of cytopharmaceuticals.
Subject(s)
Nanoparticles , Neoplasms , Photochemotherapy , Humans , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Photochemotherapy/methods , Drug Delivery Systems/methods , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Neoplasms/drug therapy , LasersABSTRACT
BACKGROUND: Chemodynamic therapy (CDT) relying on intracellular iron ions and H2O2 is a promising therapeutic strategy due to its tumor selectivity, which is limited by the not enough metal ions or H2O2 supply of tumor microenvironment. Herein, we presented an efficient CDT strategy based on Chinese herbal monomer-dihydroartemisinin (DHA) as a substitute for the H2O2 and recruiter of iron ions to amplify greatly the reactive oxygen species (ROS) generation for synergetic CDT-ferroptosis therapy. RESULTS: The DHA@MIL-101 nanoreactor was prepared and characterized firstly. This nanoreactor degraded under the acid tumor microenvironment, thereby releasing DHA and iron ions. Subsequent experiments demonstrated DHA@MIL-101 significantly increased intracellular iron ions through collapsed nanoreactor and recruitment effect of DHA, further generating ROS thereupon. Meanwhile, ROS production introduced ferroptosis by depleting glutathione (GSH), inactivating glutathione peroxidase 4 (GPX4), leading to lipid peroxide (LPO) accumulation. Furthermore, DHA also acted as an efficient ferroptosis molecular amplifier by direct inhibiting GPX4. The resulting ROS and LPO caused DNA and mitochondria damage to induce apoptosis of malignant cells. Finally, in vivo outcomes evidenced that DHA@MIL-101 nanoreactor exhibited prominent anti-cancer efficacy with minimal systemic toxicity. CONCLUSION: In summary, DHA@MIL-101 nanoreactor boosts CDT and ferroptosis for synergistic cancer therapy by molecular amplifier DHA. This work provides a novel and effective approach for synergistic CDT-ferroptosis with Chinese herbal monomer-DHA and Nanomedicine.
Subject(s)
Ferroptosis , Neoplasms , Artemisinins , Cell Line, Tumor , Glutathione , Humans , Hydrogen Peroxide , Iron , Nanomedicine , Neoplasms/drug therapy , Reactive Oxygen Species/metabolism , Tumor MicroenvironmentABSTRACT
Immunotherapy that activates the host immune system to reverse immunosuppression has emerged as a new generation of cancer treatment in both preclinical studies and clinical trials. Although immunotherapy has shown significant achievements in the treatment of various cancers, it faces challenges that limit its further evolution such as poor permeation and modest responsiveness. The development of nanoparticle drug delivery system has provided an opportunity to overcome these drawbacks and to achieve optimized immunotherapy. Based on the research of our group, we here introduce the new strategies being employed using nanoscale intelligent drug delivery systems to enhance the effects of cancer immunotherapy. We also provide a perspective on the further possible application of nanoparticles in more effective antitumor immunotherapy.
Subject(s)
Immunosuppressive Agents/therapeutic use , Immunotherapy , Neoplasms/therapy , Humans , Immunosuppression Therapy , Immunosuppressive Agents/immunology , Neoplasms/immunology , Neoplasms/pathology , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunologyABSTRACT
AIM: To explore changes in anxiety and work stress among new nurses in the first year of a 2-year residency programme. BACKGROUND: Few studies have examined the anxiety and work stress of new nurses in a residency programme. METHODS: This longitudinal study examined levels of anxiety and work stress among newly employed nurses over 1 year at 1 week and 1, 2, 3, 6, 9 and 12 months. Participants were purposively sampled from a medical centre in Taiwan. The Beck Anxiety Inventory and the Nurse Stress Checklist were used to measure anxiety and stress, respectively. RESULTS: The nurses (N = 200) generally perceived mild levels of anxiety and moderate work stress. However, anxiety and stress peaked at the first and second months. Levels stabilized by the sixth month. General ward nurses perceived higher stress levels than did those in emergency or operating rooms. CONCLUSIONS: Stress and work anxiety for new nurses peaked at 1-2 months of employment. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers, preceptors and educators must work together with newly employed nurses in individualized learning and support, doing so to improve the transition experience and reduce levels of work stress and anxiety.
Subject(s)
Internship and Residency , Nurses , Anxiety/etiology , Humans , Longitudinal Studies , TaiwanABSTRACT
BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths primarily due to chemoresistance. Somatic mutation of TP53 (36%) and epidermal growth factor receptor (EGFR; > 30%) are major contributors to cisplatin (CDDP) resistance. Substantial evidence suggests the elevated levels of reactive oxygen species (ROS) is a key determinant in cancer. The elevated ROS can affect the cellular responses to chemotherapeutic treatments. Although the role of EGFR in PI3K/Akt signaling cascade in NSCLC is extensively studied, the molecular link between EGFR and p53 and the role of ROS in pathogenesis of NSCLC are limitedly addressed. In this study, we investigated the role of p53 in regulation of ROS production and EGFR signaling, and the chemosensitivity of NSCLC. METHODS: In multiple NSCLC cell lines with varied p53 and EGFR status, we compared and examined the protein contents involved in EGFR-Akt-P53 signaling loop (EGFR, P-EGFR, Akt, P-Akt, p53, P-p53) by Western blot. Apoptosis was determined based on nuclear morphological assessment using Hoechst 33258 staining. Cellular ROS levels were measured by dichlorofluorescin diacetate (DCFDA) staining followed by flow cytometry analysis. RESULTS: We have demonstrated for the first time that activation of p53 sensitizes chemoresistant NSCLC cells to CDDP by down-regulating EGFR signaling pathway and promoting intracellular ROS production. Likewise, blocking EGFR/PI3K/AKT signaling with PI3K inhibitor elicited a similar response. Our findings suggest that CDDP-induced apoptosis in chemosensitive NSCLC cells involves p53 activation, leading to suppressed EGFR signaling and ROS production. In contrast, in chemoresistant NSCLC, activated Akt promotes EGFR signaling by the positive feedback loop and suppresses CDDP-induced ROS production and apoptosis. CONCLUSION: Collectively, our study reveals that the interaction of the p53 and Akt feedback loops determine the fate of NSCLC cells and their CDDP sensitivity.
ABSTRACT
Studies show that Paracoccus denitrificans can denitrify nitrogen sources under aerobic conditions. However, the lack of data on its genome sequence has restricted molecular studies and practical applications. In this study, the complete genome of P. denitrificans ATCC 19367 was sequenced and its nitrogen metabolism properties were characterized. The size of the whole genome is 5 242 327 bp, with two chromosomes and one plasmid. The average G + C content is 66.8%, and it contains 5308 protein-coding genes, 54 tRNA genes, and nine rRNA operons. Among the protein-coding genes, 71.35% could be assigned to the Gene Ontology (GO) pathway, 86.66% to the Clusters of Orthologous Groups (COG) pathway, and 50.57% to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Comparative genome analysis between P. denitrificans ATCC 19367 and P. denitrificans PD1222 revealed that there are 428 genes specific to ATCC 19367 and 4738 core genes. Furthermore, the expression of genes related to denitrification, biofilm formation, and nitrogen metabolism (nar, nir, and nor) by P. denitrificans ATCC 19367 under aerobic conditions was affected by incubation time and shaking speed. This study elucidates the genomic background of P. denitrificans ATCC 19367 and suggests the possibility of controlling nitrogen pollution in the environment by using this bacterium.
Subject(s)
Denitrification , Paracoccus denitrificans/genetics , Whole Genome Sequencing , Base Sequence , Genome, Bacterial , Paracoccus denitrificans/metabolismABSTRACT
BACKGROUND: Pneumatic injections of non-cross-linked hyaluronic acid are effective in skin rejuvenation, however, the associated biophysical parameters and appearance have not been evaluated. OBJECTIVES: To determine the changes in skin biophysical parameters after facial pneumatic injections of non-cross-linked hyaluronic acid. PATIENTS AND METHODS: Twenty-eight healthy female volunteers received pneumatic injections of non-cross-linked hyaluronic acid into the face for consecutive 5 weeks. Skin biophysical parameter assessment and clinical evaluation were performed using the CK Multi-Probe Adapter and Visia system. Five of the volunteers also underwent retroauricular skin biopsy before and after the last treatment. The skin tissues were all stained with Masson-trichrome, Verhoeff-van Gieson stain, and hematoxylin-eosin to evaluate the changes in collagen, elastic fibers, and the epidermis, before and after the last treatment. RESULTS: Transepidermal water loss was significantly lower in week 4 (18.46 ± 4.70 g/h/m2) than at the baseline (22.03 ± 7.15 g/h/m2, p < 0.05). Skin texture was better in week 4 (599.29 ± 354.32) than at the baseline (668.43 ± 342.55, p < 0.05). Skin pores also improved significantly at week 4 (934.07 ± 458.78) compared to the baseline (1024.57 ± 415.31, p < 0.05). Skin wrinkles were improved at the 3-month follow-up (29.29 ± 11.11) compared to the baseline (35.83 ± 16.05, p < 0.05). CONCLUSION: Pneumatic injections of non-cross-linked hyaluronic acid improved skin TEWL, texture, pores, and wrinkles.
Subject(s)
Cosmetic Techniques/instrumentation , Hyaluronic Acid/therapeutic use , Skin Aging , Adult , Aged , Collagen/drug effects , Cosmetic Techniques/adverse effects , Elastic Tissue/drug effects , Epidermis/drug effects , Female , Humans , Hyaluronic Acid/administration & dosage , Injections, Jet , Middle Aged , Patient Satisfaction , Rejuvenation , Single-Blind MethodABSTRACT
BACKGROUND: Paragonimiasis is a typical food-borne zoonotic disease. Hosts acquire Paragonimus infection through the ingestion of raw or undercooked crayfish and crab. The clinical manifestations of the disease are varied, and it is often misdiagnosed or missed. The diagnosis of paragonimiasis should be considered comprehensively. Praziquantel is the first choice for treatment, and albendazole can be used in combination with repeated courses in severe cases. CASE SUMMARY: We report a case of liver paragonimiasis that was misdiagnosed as an abscess. The patient presented with fatigue and poor appetite for 2 months, and was diagnosed with liver abscess in the local hospital. After 6 months, the patient visited our hospital because of recurrent abdominal pain and was diagnosed with liver paragonimiasis based on epidemiological history, clinical presentations, and laboratory findings. He was treated with praziquantel (25 mg/kg) three times a day for 3 days; however, the symptoms still presented after treatment. He was treated with oral praziquantel and albendazole for one further course. Follow-up suggested that the treatment was effective and the symptoms improved. CONCLUSION: The combination of albendazole and praziquantel may improve the therapeutic efficacy of paragonimiasis.
ABSTRACT
OBJECTIVE: To evaluate the clinical and prognostic value of prothrombin time (PT) and activated partial thromboplastin time (APTT) in newly diagnosed patients with multiple myeloma (MM). METHODS: The clinical data of 116 newly diagnosed MM patients in the Second Hospital and Third Hospital of Shanxi Medical University from October 2014 to March 2022 were analyzed retrospectively, and the patients were divided into two groups: normal PT and APTT group and prolonged PT or APTT group. The differences in sex, age, classification, staging, bleeding events, laboratory indicators [including hemoglobin (Hb), platelet count (PLT), serum calcium, serum albumin (ALB), lactate dehydrogenase (LDH), serum creatinine and ß2-microglobulin], and cytogenetic characteristics between the two groups of patients were compared. The effect of prolonged PT or APTT on survival of patients with MM was analyzed. RESULTS: Compared with patients in normal PT and APTT group, patients in prolonged PT or APTT group were more likely to experience bleeding events (χ2=5.087, P =0.024), with lower ALB levels (χ2=4.962, P =0.026) and PLT levels (χ2=4.309, P =0.038), and higher serum calcium levels (χ2=5.056, P =0.025). The positive rates of del17p, del13q and 1q21+ in prolonged PT or APTT group were higher than those in normal PT and APTT group, but the difference was not statistically significant (P >0.05). K-M survival analysis showed that the prolonged PT or APTT group had a shorter median progression-free survival (PFS) (P =0.032) and overall survival (OS) (P =0.032). Multivariate Cox analysis showed that prolonged PT or APTT (HR=2.116, 95%CI :1.025-4.372, P =0.043) and age ≥65 years (HR=2.403, 95%CI : 1.195-4.836, P =0.014) were independent risk factor for OS in newly diagnosed MM patients. However, prolonged PT or APTT had no significant effect on PFS of newly diagnosed MM patients (HR=1.162, 95%CI : 0.666-2.026, P =0.597). CONCLUSION: Newly diagnosed MM patients with prolonged PT or APTT have worse clinical indicators, shorter PFS and OS. Prolonged PT or APTT is an independent risk factor for OS in MM patients.
Subject(s)
Multiple Myeloma , Prothrombin Time , Humans , Multiple Myeloma/blood , Multiple Myeloma/diagnosis , Partial Thromboplastin Time , Prognosis , Retrospective Studies , Male , Female , Middle AgedABSTRACT
OBJECTIVE: Photodynamic therapy (PDT) primarily treats skin diseases or cancer by generating reactive oxygen species (ROS) to damage cellular DNA, yet drug resistance limits its application. To tackle this problem, the present study was carried out to improve the efficacy of chlorin e6 (Ce6)-PDT using Cepharanthine (CEP) as well as to reveal the potential molecular mechanism. MATERIALS AND METHODS: Lewis lung cancer cell line (LLC) was utilized as the cancer cell model. chlorin e6 (Ce6) acted as the photosensitizer to induce PDT. The in vitro anti-cancer efficacy was measured by CCK-8, Annexin-V/PI staining, and migration assay. The Ce6 uptake was observed using flow cytometry and confocal microscopy. The ROS generation was detected by the DCFH-DA probe. The analysis of MutT Homolog 1 (MTH1) expression, correlation, and prognosis in databases was conducted by bioinformatic. The MTH1 expression was detected through western blots (WB). DNA damage was assayed by WB, immunofluorescent staining, and comet assay. RESULTS: Ce6-PDT showed robust resistance in lung cancer cells under certain conditions, as evidenced by the unchanged cell viability and apoptosis. The subsequent findings confirmed that the uptake of Ce6 and MTH1 expression was enhanced, but ROS generation with laser irradiation was not increased in LLC, which indicated that the ROS scavenge may be the critical reason for resistance. Surprisingly, bioinformatic and in vitro experiments identified that MTH1, which could prevent the DNA from damage of ROS, was highly expressed in lung cancer and thereby led to the poor prognosis and could be further up-regulated by Ce6 PDT. CEP exhibited a dose-dependent suppressive effect on the lung cancer cells. Further investigations presented that CEP treatment boosted ROS production, thereby resulting in DNA double-strand breakage (DDSB) with activation of MTH1, indicating that CEP facilitated Ce6-PDT-mediated DNA damage. Finally, the combination of CEP and Ce6-PDT exhibited prominent ROS accumulation, MTH1 inhibition, and anti-lung cancer efficacy, which had synergistic pro-DNA damage properties. CONCLUSION: Collectively, highly expressed MTH1 and the failure of ROS generation lead to PDT resistance in lung cancer cells. CEP facilitates ROS generation of PDT, thereby promoting vigorous DNA damage, inactivating MTH1, alleviating PDT resistance, and ameliorating the anti-cancer efficacy of Ce6-PDT, provides a novel approach for augmented PDT.
Subject(s)
Benzodioxoles , Benzylisoquinolines , Lung Neoplasms , Photochemotherapy , Humans , Photosensitizing Agents/therapeutic use , Photochemotherapy/methods , Reactive Oxygen Species/metabolism , Cell Line, Tumor , Lung Neoplasms/drug therapy , DNA Damage , DNAABSTRACT
BACKGROUND: Severe endoplasmic reticulum (ER) stress elicits apoptosis to suppress lung cancer. Our previous research identified that Cepharanthine (CEP), a kind of phytomedicine, possessed powerful anti-cancer efficacy, for which the underlying mechanism was still uncovered. Herein, we investigated how CEP induced ER stress and worked against lung cancer. METHODS: The differential expression genes (DEGs) and enrichment were detected by RNA-sequence. The affinity of CEP and NRF2 was analyzed by cellular thermal shift assay (CETSA) and molecular docking. The function assay of lung cancer cells was measured by western blots, flow cytometry, immunofluorescence staining, and ferroptosis inhibitors. RESULTS: CEP treatment enriched DEGs in ferroptosis and ER stress. Further analysis demonstrated the target was NRF2. In vitro and in vivo experiments showed that CEP induced obvious ferroptosis, as characterized by the elevated iron ions, ROS, COX-2 expression, down-regulation of GPX4, and atrophic mitochondria. Moreover, enhanced Grp78, CHOP expression, ß-amyloid mass, and disappearing parallel stacked structures of ER were observed in CEP group, suggesting ER stress was aroused. CEP exhibited excellent anti-lung cancer efficacy, as evidenced by the increased apoptosis, reduced proliferation, diminished cell stemness, and prominent inhibition of tumor grafts in animal models. Furthermore, the addition of ferroptosis inhibitors weakened CEP-induced ER stress and apoptosis. CONCLUSION: In summary, our findings proved CEP drives ferroptosis through inhibition of NRF2 for induction of robust ER stress, thereby leading to apoptosis and attenuated stemness of lung cancer cells. The current work presents a novel mechanism for the anti-tumor efficacy of the natural compound CEP.
Subject(s)
Benzylisoquinolines , Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress , Ferroptosis , Lung Neoplasms , NF-E2-Related Factor 2 , Benzylisoquinolines/pharmacology , Benzylisoquinolines/therapeutic use , Endoplasmic Reticulum Stress/drug effects , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Ferroptosis/drug effects , Lung Neoplasms/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/genetics , Humans , Animals , Mice , Cell Line, Tumor , Xenograft Model Antitumor Assays , A549 Cells , Gene Expression Regulation, Neoplastic/drug effects , Molecular Docking Simulation , BenzodioxolesABSTRACT
OBJECTIVE: To compare the short-term effect and adverse reaction of venetoclax (VEN) combined with azacitidine (AZA) versus "7+3" regimen in newly diagnosed elder patients with acute myeloid leukemia (AML). METHODS: From January 2021 to January 2022, the clinical data of seventy-nine newly diagnosed elder patients with AML at the Second Hospital of Shanxi Medical University and the Shanxi Bethune Hospital were retrospectively analyzed, including VEN+AZA group (41 cases) and "7+3" group (38 cases). The propensity score matching(PSM) method was used to balance confounding factorsï¼ then responseï¼ overall survival(OS), progressionîfree survival(PFS) and adverse reactions between the two groups were compared. RESULTS: The ORR of VEN+AZA group and "7+3" group was 68% and 84%, respectively, and the CRc was 64% and 72%, respectively, the differents were not statistically significant (P >0.05). In the VEN+AZA group, there were 5 non-remission (NR) patients, 4 with chromosome 7 abnormality (7q-/-7), and 1 with ETV6 gene mutation. Median followed-up time between the two groups was 8 months and 12 months, respectively, and the 6-months OS was 84% vs 92% (P =0.389), while 6-months PFS was 84% vs 92% (P =0.258). The main hematological adverse reactions in two groups were stage â ¢-â £ myelosuppression, and the incidence rate was not statistically different(P >0.05). The median time of neutrophil recovery in two groups was 27(11-70) d, 25(14-61) d ï¼P =0.161ï¼, and platelet recovery was 27(11-75) d, 25(16-50) d ï¼P =0.270ï¼, respectively. The infection rate of VEN+AZA group was lower than that of "7+3" group (56% vs 88%, P =0.012ï¼. The rate of lung infections of two groups was 36% and 64%, respectively, the difference was statistically significant (P =0.048). CONCLUSION: The short-term effect of VEN+AZA group and "7+3" regimens in eldrly AML patients are similarï¼ but the VEN+AZA regimen had a lower incidence of infection. The presence of chromosome 7 abnormalityï¼7q-/-7ï¼ may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.
Subject(s)
Azacitidine , Leukemia, Myeloid, Acute , Sulfonamides , Aged , Humans , Retrospective Studies , Bridged Bicyclo Compounds, Heterocyclic , Leukemia, Myeloid, Acute/drug therapy , Chromosome Aberrations , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
[This corrects the article DOI: 10.3389/fpsyg.2022.1026317.].
ABSTRACT
OBJECTIVE: To analyze the clinical characteristics of venous thromboembolism (VTE) in patients with multiple myeloma (MM) and to identify the risk factors of VTE in MM patients. METHODS: 179 newly diagnosed MM (NDMM) patients admitted to The Second Hospital of Shanxi Medical University from January 2014 to December 2020 who were followed up for more than 6 months were collected, and they were divided into VTE group and control group according to whether combined with VTE. The clinical and laboratory data were compared between the two groups. Mann-whitney U test was used for inter-group comparison of measurement data, Chi-square test or Fisher's exact test was used for inter-group comparison of count data, and multivariate logistic regression analysis was performed to explore the risk factors of VTE in MM patients. RESULTS: Compared with control group, the serum albumin (ALB) level in VTE group was significantly lower (P =0.033), the fibrinogen (FIB) level was significantly higher (P =0.016), and the proportion of patients with D-dimer≥2 000 ng/ml was significantly higher than that in the control group (26.3% vs 4.4%, P =0.002). There was a significant difference in M-component type between the two groups (P =0.028), and the proportion of IgG type in VTE group was higher. There were no statistically significant differences between two groups in age, sex, body mass index (BMI), the proportions of patients with hypertension, diabetes, coronary heart disease and cerebral infarction, white blood cell (WBC) count, platelet (PLT) count, liver and kidney function, plasma cells ratio in bone marrow, serum globulin (GLO), lactate dehydrogenase (LDH), ß2-microglobulin (ß2-MG) level, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), prothrombin time (PT), activated partial thromboplastin time (APTT), disease stage, thrombosis prevention and the use of immunomodulators (P >0.05). Multivariate logistic regression analysis showed that FIB level (OR=1.578, 95%CI:1.035-2.407, P =0.034), D-dimer≥2 000 ng/ml (OR=5.467, 95%CI:1.265-23.621, P =0.023) and IgG type (OR=4.780, 95%CI: 1.221-18.712, P =0.025) were independent risk factors for VTE in MM patients. CONCLUSION: MM patients are prone to VTE, and FIB level, D-dimer≥2 000 ng/ ml and IgG type are independent risk factors for VTE in MM patients.
Subject(s)
Multiple Myeloma , Venous Thromboembolism , Humans , Multiple Myeloma/complications , Risk Factors , Anticoagulants , Immunoglobulin G , Retrospective StudiesABSTRACT
OBJECTIVE: To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis. METHODS: A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ï¼»66 cases of them were screened by propensity score matching (PSM), as control groupï¼½. The early efficacy and survival between the two groups were compared. RESULTS: The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×109/L, among which 15 cases (68.18%) were >10×109/L, and the median count of platelet (PLT) was 24(4-55)×109/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively. CONCLUSION: Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.
Subject(s)
Leukemia, Myeloid, Acute , Leukemia, Myelomonocytic, Acute , Middle Aged , Humans , Male , Female , Aged , Retrospective Studies , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/diagnosis , Prognosis , Mutation , Receptors, Colony-Stimulating Factor/geneticsABSTRACT
Suppression of the immune microenvironment is an important endogenous contributor to treatment failure in lung cancer. Photodynamic therapy (PDT) is widely used in the treatment of malignant tumors owing to its photo-selectivity and minimal side effects. Some studies have shown the ability of photodynamic action not only to cause photo-cytotoxicity to tumor cells but also to induce immunogenic cell death (ICD). However, the mechanism by which PDT enhances tumor immunogenicity is poorly understood. The present study aimed to explore the immunogenicity effect of PDT on lung cancer and to reveal the underlying mechanism. First, we searched for effective conditions for PDT-induced apoptosis in lung cancer cells. Just as expected, chlorin e6 (Ce6) PDT could enhance the immunogenicity of lung cancer cells alongside the induction of apoptosis, characterized by up-regulation of CRT, HSP90, HMGB1 and MHC-I. Further results showed the generation of ROS by Ce6 PDT under the above conditions, which is an oxidative damaging agent. Simultaneously, PDT induced endoplasmic reticulum (ER) stress in cells, as evidenced by enhanced Tht staining and up-regulated CHOP and GRP78 expression. Moreover, PDT led to DNA damage response (DDR) as well. However, the redox inhibitor NAC abolished the ER stress and DDR caused by PDT. More importantly, NAC also attenuated PDT-induced improvement of immunogenicity in lung cancer. On this basis, the PDT-induced CRT up-regulation was found to be attenuated in response to inhibition of ER stress. In addition, PDT-induced increase in HMGB1 and HSP90 release was blocked by inhibition of DDR. In summary, Ce6 PDT could produce ROS under certain conditions, which leads to ER stress that promotes CRT translocation to the cell membrane, and the resulting DNA damage causes the expression and release of nuclear HMGB1 and HSP90, thereby enhancing the immunogenicity of lung cancer. This current study elucidates the mechanism of PDT in ameliorating the immunogenicity of lung cancer, providing a rationale for PDT in regulating the immune microenvironment for the treatment of malignant tumors.
Subject(s)
HMGB1 Protein , Lung Neoplasms , Photochemotherapy , Humans , Photochemotherapy/methods , Reactive Oxygen Species , Immunogenic Cell Death , Lung Neoplasms/drug therapy , Oxidative Stress , Endoplasmic Reticulum Stress , DNA Damage , Oxidation-Reduction , Cell Line, Tumor , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Tumor MicroenvironmentABSTRACT
BACKGROUND: The immunosuppressive microenvironment of lung cancer serves as an important endogenous contributor to treatment failure. The present study aimed to demonstrate the promotive effect of DHA on immunogenic cell death (ICD) in lung cancer as well as the mechanism. METHODS: The lewis lung cancer cells (LLC), A549 cells and LLC-bearing mice were applied as the lung cancer model. The apoptosis, ferroptosis assay, western blotting, immunofluorescent staining, qPCR, comet assay, flow cytometry, confocal microscopy, transmission electron microscopy and immunohistochemistry were conducted to analyze the functions and the underlying mechanism. RESULTS: An increased apoptosis rate and immunogenicity were detected in DHA-treated LLC and tumor grafts. Further findings showed DHA caused lipid peroxide (LPO) accumulation, thereby initiating ferroptosis. DHA stimulated cellular endoplasmic reticulum (ER) stress and DNA damage simultaneously. However, the ER stress and DNA damage induced by DHA could be abolished by ferroptosis inhibitors, whose immunogenicity enhancement was synchronously attenuated. In contrast, the addition of exogenous iron ions further improved the immunogenicity induced by DHA accompanied by enhanced ER stress and DNA damage. The enhanced immunogenicity could be abated by ER stress and DNA damage inhibitors as well. Finally, DHA activated immunocytes and exhibited excellent anti-cancer efficacy in LLC-bearing mice. CONCLUSIONS: In summary, the current study demonstrates that DHA triggers ferroptosis, facilitating the ICD of lung cancer thereupon. This work reveals for the first time the effect and underlying mechanism by which DHA induces ICD of cancer cells, providing novel insights into the regulation of the immune microenvironment for cancer immunotherapy by Chinese medicine phytopharmaceuticals.
Subject(s)
Carcinoma, Lewis Lung , Ferroptosis , Lung Neoplasms , Animals , Mice , Lung Neoplasms/drug therapy , Carcinoma, Lewis Lung/drug therapy , Endoplasmic Reticulum Stress , Immunotherapy , DNA Damage , Tumor MicroenvironmentABSTRACT
Background: Nurses are in high-pressure, high-load, and high-risk environment for a long time, and their insomnia cannot be ignored. Insomnia not only has a negative impact on the physical and mental health of nurses, but also on the efficiency and quality of nursing work. Objective: The purpose of this study was to investigate the multiple mediating effect of psychological capital, effort-reward ratio, and overcommitment in the relationship between perceived organizational support and insomnia among Chinese nurses. Methods: A cross-sectional study has been carried out in a tertiary grade A hospital in Shandong Province, China from March 2021 to May 2021. The demographic questionnaire, Perceived Organization Support Questionnaire, Psychological Capital Questionnaire, Chinese version Effort-Reward Imbalance, Questionnaire and Athens Insomnia Scale were used for data collection. SPSS PROCESS 3.4 macro program developed by Hayes was used to test the serial multiple mediation. Descriptive analysis, independent-samples t-test, one-way analysis of variance, Pearson's correlation analyses, ordinary least-squares regression, and the bootstrap method were used for data analysis. Results: 658 valid questionnaires were collected (81.2%). Nurses' perceived organizational support was positively correlated with psychological capital (r = 0.455, p < 0.001), and was significantly negatively correlated with effort-reward ratio (r = -0.318, p < 0.001), overcommitment (r = -0.328, p < 0.001), and insomnia (r = -0.358, p < 0.001); Psychological capital was negatively correlated with effort-reward ratio (r = -0.275, p < 0.001), overcommitment (r = -0.339, p < 0.001), and insomnia (r = -0.402, p < 0.001), respectively; effort-reward ratio and overcommitment were significantly positively correlated with insomnia (r = 0.379, p < 0.001; r = 0.466, p < 0.001), respectively. In the model of perceived organizational support-psychological capital-effort-reward ratio-insomnia, the overall mediating effect was -0.080 (95%CI: -0.109 ~ -0.058), and the mediating effect of psychological capital was -0.050, accounting for 34.30% of the total effect; the mediating effect of effort-reward ratio was -0.024, accounting for 16.49% of the total effect; the chain mediating effect of psychological capital and effort-reward ratio was -0.007, accounting for 4.49% of the total effect. In the model of perceived organizational support-psychological capital-overcommitment-insomnia, the overall mediating effect was -0.085 (95%CI: -0.109 ~ -0.064), and the mediating effect of psychological capital was -0.042, accounting for 28.64% of the total effect; the mediating effect of overcommitment was -0.029, accounting for 19.81% of the total effect; the chain mediating effect of psychological capital and overcommitment was -0.015, accounting for 10.14% of the total effect. Conclusion: Perceived organizational support had direct negative influence on insomnia. Psychological capital and effort-reward ratio/overcommitment acted as chained mediating factor could partially relieve insomnia symptoms related to perceived organizational support. It is suggested to improve the level of organizational support and psychological capital of nurses, and reduce the effort-reward imbalance and overcommitment of nurses, so as to effectively decline and deal with nurses' insomnia.
ABSTRACT
Background: Nurses have a high incidence of insomnia. Insomnia not only damages the physical and mental health of nurses, but also reduces their productivity and quality of care, ultimately affecting patient care. Over the past 30 years, a large number of epidemiological surveys have shown that insomnia in nurses is associated with occupational stress. As an external feature of the role of a nurse, occupational stress is difficult to alter in a short period of time. Therefore, it is necessary to discuss the complex mediating variables in the relationship between occupational stress and insomnia in nurses in order to find different ideas to address the problem of insomnia caused by occupational stress. Psychological capital, the positive psychological strength of an individual, has been widely used in previous reports as a mediating variable between occupational stress and adverse psychological problems. Objective: This study aimed to explore the mediating effect of psychological capital on occupational stressors and insomnia among Chinese nurses. Methods: The Strengthening the Reporting of Observational Studies in Epidemiology statement was referred to conduct the study. A cross-sectional stratified sampling method was used to recruit 720 participants from a tertiary hospital in Jinan, Shandong province, located in the east of China, from June to August 2019. Questionnaires were used to obtain data on demographic variables, psychological capital, occupational stressors, and insomnia. Results: The study findings revealed that work settings [department (F = 3.08, p = 0.006), working hours per week (t = -2.03, p = 0.043) and shift work (t = 3.66, p < 0.001)], decision latitude (r = -0.25, p < 0.001), psychological job demand (r = 0.15, p < 0.001), social support (r = -0.31, p < 0.001), and psychological capital (r = -0.40, p < 0.001) were differentially associated with insomnia experiences. This cross-sectional survey showed that psychological capital has significant mediation effects on the relationship between occupational stressors and insomnia. In the model of decision latitude - psychological capital - insomnia, the mediating effect was-0.04 (95%CI: -0.07 ~ -0.02), accounting for 50.0% of the total effect; In the model of job demands - psychological capital - insomnia, the mediating effect was 0.03 (95%CI: 0.01 ~ 0.06), accounting for 25.0% of the total effect; In the model of social support - psychological capital - insomnia, the mediating effect was -0.11 (95%CI: -0.16 ~ -0.07), accounting for 39.0% of the total effect. Conclusion: Psychological capital not only had a direct effect on both occupational stressors and insomnia, but also played mediating roles in relationship between occupational stressors and insomnia. It has been suggested that nurses themselves and nursing managers should improve the psychological capital of nurses by various means to alleviate the effects of occupational stress on nurses' insomnia.