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Lappanolides A-N (1-14), 14 undescribed sesquiterpenoids, along with 23 known ones (15-37), were isolated from the roots of Saussurea costus, which were primarily categorized into eudesmane, guaiane, and germacrane types. Lappanolide A (1) possessed an unprecedented pseudo-disesquiterpenoids. Their structures and absolute configurations were established using physical data analyses (HRESIMS, IR, 1D and 2D NMR) and ECD calculations. All isolated compounds were tested for anti-hepatitis B virus (anti-HBV) activity. Ten compounds (1, 9, 11, 12, 19, 22, 28, 29, 31, and 36) exhibited activities against HBsAg secretions as determined by ELISA assay, with IC50 values ranging from 5.2 to 45.7 µM. In particular, compounds 28 and 29 showed inhibition of HBsAg secretion with IC50 values of 5.28 and 5.30 µM, and CC50 values of 9.85 and 6.37 µM, respectively, though they all exhibited low selectivity. Several compounds displayed cytotoxicity in the MTT assay. Among them, compound 28 was the most notable and was chosen for further study using flow cytometry. The result showed that it significantly induced HepG2 cell arrest in the S phase and induced apoptosis.
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Antivirales , Virus de la Hepatitis B , Saussurea , Sesquiterpenos , Saussurea/química , Humanos , Virus de la Hepatitis B/efectos de los fármacos , Antivirales/farmacología , Antivirales/química , Antivirales/aislamiento & purificación , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Células Hep G2 , Estructura Molecular , Antígenos de Superficie de la Hepatitis B/metabolismo , Antígenos de Superficie de la Hepatitis B/efectos de los fármacos , Relación Estructura-Actividad , Raíces de Plantas/química , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Apoptosis/efectos de los fármacosRESUMEN
Phototherapy promotes anti-tumor immunity by inducing immunogenic cell death (ICD), However, the accompanying inflammatory responses also trigger immunosuppression, attenuating the efficacy of photo-immunotherapy. Herein, they co-assembled a cell-membrane targeting chimeric peptide C16-Cypate-RRKK-PEG8-COOH (CCP) and anti-inflammatory diclofenac (DA) to develop a nanodrug (CCP@DA) that both enhances the immune effect of phototherapy and weakens the inflammation-mediated immunosuppression. CCP@DA achieves cell membrane-targeting photodynamic and photothermal synergistic therapies to damage programmed death ligand 1 (PD-L1) and induce a strong ICD to activate anti-tumor response. Simultaneously, the released DA inhibits the cycoperoxidase-2 (COX-2)/prostaglandin E2 (PGE2) pathway in tumor cells to inhibit pro-tumor inflammation and further down-regulate PD-L1 expression to relieve the immunosuppressive microenvironment. CCP@DA significantly inhibited tumor growth and inflammation both in vitro and in vivo, while maintaining a potent anti-tumor immune response. Additionally, it exhibits excellent anti-metastatic capabilities and prolongs mouse survival time with a single dose and low levels of near-infrared (NIR) light exposure. This work provides a valuable strategy to control the therapy-induced inflammation for high-efficiency photoimmunotherapy.
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Antígeno B7-H1 , Ciclooxigenasa 2 , Dinoprostona , Inmunoterapia , Inflamación , Animales , Antígeno B7-H1/metabolismo , Ratones , Dinoprostona/metabolismo , Inmunoterapia/métodos , Ciclooxigenasa 2/metabolismo , Línea Celular Tumoral , Humanos , Diclofenaco/farmacología , Diclofenaco/administración & dosificación , Fototerapia/métodos , Nanopartículas/química , Regulación hacia Abajo/efectos de los fármacos , Fotoquimioterapia/métodosRESUMEN
OBJECTIVE: Azvudine is an effective treatment for patients infected with common COVID-19. However, physicians have reported a series of adverse reactions, including multiple cases of liver injury, caused by azvudine in clinical practice. This study assessed the incidence, clinical features, and associated risk factors of liver injury induced by azvudine in real-world settings, offering guidance for safe clinical use. MATERIALS AND METHODS: This study utilized the Chinese Hospital Pharmacovigilance System (CHPS) to retrospectively analyze the treatment of COVID-19 patients with azvudine at Changsha Central Hospital from December 19, 2022, to June 6, 2023. A case-control study was conducted to analyze the occurrence of azvudine-induced liver injury in COVID-19 patients who triggered a CHPS alert compared to normal COVID-19 patients. RESULTS: Among the total of 2,141 COVID-19 patients, 31 (1.45%) developed azvudine-induced liver injury, which is classified as an occasional adverse reaction. Liver injury was observed in 93.55% of patients between days 4 and 12 of the azvudine treatment, with elevated transaminases as the primary clinical manifestation. Univariate and binary logistic regression analyses indicated that low albumin levels and co-administration of low-molecular-weight heparin were statistically significant risk factors (p < 0.05). CONCLUSION: This study represents the first investigation of azvudine-induced liver injury and high-risk patients using the CHPS. The findings provide valuable insights to promote the safety of anti-COVID-19 drugs, serving as an important reference for future drug safety measures.
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Azidas , COVID-19 , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Desoxicitidina/análogos & derivados , Humanos , Heparina de Bajo-Peso-Molecular/efectos adversos , Farmacovigilancia , Estudios Retrospectivos , Estudios de Casos y Controles , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/tratamiento farmacológico , Estudios Prospectivos , Factores de Riesgo , AlbúminasRESUMEN
Objective To investigate the clinical value of Yishen Gujing Kangyan Prescription(with the actions of benefiting the kidneys,consolidating essence and anti-inflammatory,mainly composed of Imperatae Rhizoma,Codonopsis Radix,Corni Fructus,Moutan Cortex,Lycii Fructus,Cuscutae Semen,Dioscoreae Rhizoma,honey-roasted Astragali Radix,Poria,Rehmanniae Radix Praeparata,etc.)in the treatment of lupus nephritis(LN)of qi and yin deficiency type.Methods A total of 116 patients with LN of qi and yin deficiency type were randomly divided into observation group and control group,58 cases in each group.The control group was given conventional western medicine treatment,and the observation group was treated with the combination of Yishen Gujing Kangyan Prescription on the basis of treatment for the control group.Both groups were treated for a period of 6 months.The changes of traditional Chinese medicine(TCM)syndrome scores,renal function parameters,immune function indicators,serum interleukin 18(IL-18),homocysteine(Hcy),transforming growth factor β1(TGF-β1),cystatin C(Cys C)levels in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and the negative-conversion of anti-double-stranded DNA(ds-DNA)antibody were compared between the two groups.Results(1)After 6 months of treatment,the total effective rate of the observation group was 94.83%(55/58),and that of the control group was 75.86%(44/58).The intergroup comparison showed that the therapeutic effect of the observation group was significantly superior to that of the control group(χ2 = 5.453,P<0.05).(2)After treatment,the scores of primary symptoms(edema,fatigue)and secondary symptoms(lumbar and knee soreness,loose stools)in the two groups were lower than those before treatment(P<0.05),and the effect on lowering the scores in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the levels of renal function parameters of blood urea nitrogen(BUN),serum creatinine(Scr),and 24-hour urine protein quantification of the two groups were all lower than those before treatment(P<0.05),and the effect on lowering renal function parameters in the observation group was significantly superior to that in the control group(P<0.01).(4)After treatment,serum IL-18,TGF-β1,Hcy and Cys C levels of the two groups of patients were all reduced compared with those before treatment(P<0.05),and the effect on lowering the levels of inflammatory factors and fibrosis parameters in the observation group was significantly superior to that in the control group(P<0.01).(5)After treatment,the levels of immune function indicators of T cell subsets CD4+,CD4+/CD8+ and complement C3 in the two groups were increased compared with those before treatment(P<0.05),and the increase in the observation group was significantly superior to that in the control group,and the differences were all statistically significant(P<0.05 or P<0.01).(6)The negative-conversion rate of anti-ds-DNA antibody in the observation group was 77.59%(45/58),which was significantly higher than that in the control group(55.17%,32/58),and the difference was statistically significant between the two groups(P<0.05).Conclusion For the treatment of patients with LN of qi and yin deficiency type,Yishen Gujing Kangyan Prescription exerts synergistic effect on reducing inflammatory response,regulating immune function,promoting the recovery of renal function,and enhancing clinical efficacy.
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Linezolid combined with rifampicin has shown excellent clinical outcomes against infection by multi-resistant Gram-positive bacteria. However, several studies have indicated that rifampicin reduces the plasma concentration of linezolid in patients with severe infection. Linezolid has been recommended for the treatment of patients with multidrug-resistant or extensively drug-resistant tuberculosis. However, studies on the interaction between linezolid and rifampicin in patients suffering from tuberculosis with infection are lacking. We evaluated the interaction between linezolid and rifampicin based on therapeutic drug monitoring (TDM). A retrospective analysis was undertaken for patients with tuberculosis and infection who were treated with linezolid and undergoing TDM. Patients were divided into the linezolid group and linezolid + rifampicin group. Data on demographic characteristics, disease, duration of linezolid therapy, and the plasma concentration of linezolid were used for statistical analyses. Eighty-eight patients with tuberculosis and infection were assessed. Values for the peak (Cmax) and trough (Cmin) concentrations of linezolid in plasma were available for 42 and 46 cases, respectively. Patients in the linezolid group had a significantly higher Cmax [15.76 (8.07-26.06) vs. 13.18 (7.48-23.64) mg/L, p = 0.048] and Cmin [8.38 (3.06-16.53) vs. 4.27 (0.45-10.47), p = 0.005] than those in the linezolid + rifampicin group. The plasma concentration of linezolid increased obviously in two patients after rifampicin discontinuation. However, the total efficiency and prevalence of hematologic adverse reactions were not significantly different in the linezolid group and linezolid + rifampin group. The plasma concentration of linezolid decreased upon combination with rifampicin, suggesting that TDM may aid avoidance of subtherapeutic levels of linezolid upon co-treatment with rifampicin.
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Inflammatory cytokines are known to be involved in acute ischemic stroke (AIS), while the relationship of multiple inflammatory cytokines with mental disorders in AIS is less reported. This research intended to explore the longitudinal variation of common inflammatory cytokines and their correlation with anxiety, depression, and cognitive impairment in AIS patients. Six inflammatory cytokines were detected by enzyme-linked immunosorbent assay among 175 AIS patients at admission (baseline) and on the day (D)1, D3, and D7 after admission. Anxiety, depression, and cognition were evaluated using the Hospital Anxiety and Depression Scale and Mini-Mental State Examination at discharge, respectively. Anxiety, depression, and cognitive impairment rates were 32.6, 39.4, and 19.4%, respectively. Tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, and IL-17A increased from baseline to D1, then decreased from D1 to D7 (all P<0.001), while IL-10 presented an opposite trend (P<0.001). Interestingly, TNF-α on D1 and D3, IL-6 on D3, IL-8 on D3 and D7, and IL-17A on D1, D3, and D7 correlated with higher anxiety rate (all P<0.05). TNF-α on D1, D3, and D7, IL-8 at baseline, D1, D3, and D7, IL-17A on D1 and D7 correlated with increased depression rate (all P<0.05). In addition, IL-1ß on D1 and IL-17 at baseline, D1, D3, and D7 correlated with elevated cognitive-impairment rate (all P<0.05). Inflammatory cytokines were dysregulated after disease onset, and their longitudinal change correlated with psychological issues in AIS patients.
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Disfunción Cognitiva , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Citocinas , Interleucina-17 , Factor de Necrosis Tumoral alfa , Depresión/etiología , Interleucina-6 , Interleucina-8 , Ansiedad , Disfunción Cognitiva/etiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/psicologíaRESUMEN
BACKGROUND: Patients with chronic kidney disease (CKD) undergoing coronary angiography (CAG) are at high risk of contrast-associated acute kidney injury (CA-AKI) and mortality. Therefore, there is a clinical need to explore safe, convenient, and effective strategies for preventing CA-AKI. OBJECTIVES: This study sought to assess whether simplified rapid hydration is noninferior to standard hydration for CA-AKI prevention in patients with CKD. METHODS: This multicenter, open-label, randomized controlled study was conducted across 21 teaching hospitals and included 1,002 patients with CKD. Patients were randomized to either simplified hydration (SH) (SH group, with normal saline from 1 hour before to 4 hours after CAG at a rate of 3 mL/kg/h) or standard hydration (control group, with normal saline 12 hours before and 12 hours after CAG at a rate of 1 mL/kg/h). The primary endpoint of CA-AKI was a ≥25% or 0.5-mg/dL rise in serum creatinine from baseline within 48 to 72 hours. RESULTS: CA-AKI occurred in 29 of 466 (6.2%) patients in the SH group and in 38 of 455 (8.4%) patients in the control group (relative risk: 0.8; 95% CI: 0.5-1.2; P = 0.216). In addition, the risk of acute heart failure and 1-year major adverse cardiovascular events did not differ significantly between the groups. However, the median hydration duration was significantly shorter in the SH group than in the control group (6 vs 25 hours; P < 0.001). CONCLUSIONS: In CKD patients undergoing CAG, SH is noninferior to standard hydration in preventing CA-AKI with a shorter hydration duration.
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Lesión Renal Aguda , Insuficiencia Renal Crónica , Humanos , Angiografía Coronaria/efectos adversos , Solución Salina , Resultado del Tratamiento , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/prevención & control , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnósticoRESUMEN
OBJECTIVE: The hypersensitivity of the kidney makes it susceptible to hypoxia injury. The involvement of neutrophil extracellular traps (NETs) in renal injury resulting from hypobaric hypoxia (HH) has not been reported. In this study, we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism. METHODS: A total of 24 SD male rats were divided into three groups (n=8 each): normal control group, hypoxia group and hypoxia+pyrrolidine dithiocarbamate (PDTC) group. Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters (oxygen partial pressure about 6.9 kPa) for 7 days. PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days. Pathological changes of the rat renal tissues were observed under a light microscope; the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cell-free DNA (cf-DNA) and reactive oxygen species (ROS) were measured; the expression levels of myeloperoxidase (MPO), citrullinated histone H3 (cit-H3), B-cell lymphoma 2 (Bcl-2), Bax, nuclear factor kappa B (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in rat renal tissues were detected by qRT-qPCR and Western blotting; the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining. RESULTS: After hypoxia, the expression of NF-κB protein in renal tissues was significantly increased, the levels of SCr, BUN, cf-DNA and ROS in serum were significantly increased, the formation of NETs in renal tissues was significantly increased, and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues. When PDTC was used to inhibit NF-κB activation, NETs formation in renal tissue was significantly decreased, the expression level of Bcl-2 in renal tissues was significantly increased, the expression level of Bax was significantly decreased, and renal injury was significantly alleviated. CONCLUSION: HH induces the formation of NETs through the NF-κB signaling pathway, and it promotes apoptosis and aggravates renal injury by decreasing Bcl-2 and increasing Bax expression.
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Trampas Extracelulares , FN-kappa B , Ratas , Masculino , Animales , FN-kappa B/metabolismo , Trampas Extracelulares/metabolismo , Especies Reactivas de Oxígeno , Proteína X Asociada a bcl-2/genética , Riñón/patología , Transducción de Señal , Hipoxia/patología , ADNRESUMEN
Inflammatory cytokines are known to be involved in acute ischemic stroke (AIS), while the relationship of multiple inflammatory cytokines with mental disorders in AIS is less reported. This research intended to explore the longitudinal variation of common inflammatory cytokines and their correlation with anxiety, depression, and cognitive impairment in AIS patients. Six inflammatory cytokines were detected by enzyme-linked immunosorbent assay among 175 AIS patients at admission (baseline) and on the day (D)1, D3, and D7 after admission. Anxiety, depression, and cognition were evaluated using the Hospital Anxiety and Depression Scale and Mini-Mental State Examination at discharge, respectively. Anxiety, depression, and cognitive impairment rates were 32.6, 39.4, and 19.4%, respectively. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and IL-17A increased from baseline to D1, then decreased from D1 to D7 (all P<0.001), while IL-10 presented an opposite trend (P<0.001). Interestingly, TNF-α on D1 and D3, IL-6 on D3, IL-8 on D3 and D7, and IL-17A on D1, D3, and D7 correlated with higher anxiety rate (all P<0.05). TNF-α on D1, D3, and D7, IL-8 at baseline, D1, D3, and D7, IL-17A on D1 and D7 correlated with increased depression rate (all P<0.05). In addition, IL-1β on D1 and IL-17 at baseline, D1, D3, and D7 correlated with elevated cognitive-impairment rate (all P<0.05). Inflammatory cytokines were dysregulated after disease onset, and their longitudinal change correlated with psychological issues in AIS patients.
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Aim To investigate the effects of daidzeinDD on the proliferation and apoptosis of non-small cell lung cancer cells,with a focus on the possible role of the p53 signaling pathway in this regard. Methods CCK-8 method and flow cytometry were used to detect the effects of soy isoflavone crude extract and DD on the viability and apoptosis of HELF and H1299 cells. Gene microarray was used to detect the changes in gene expression after treatment of H1299 cells with DD. GSEA and differential analysis were used to screen the major pathways and key genes. RT-qPCR and Western blot were performed to verify the differences in mRNA and protein expression of key genesp53 and CASP9 in the major pathways. After p53 inhibitor Pifithrin-α inhibited the expression of p53,the effect of DD on p53 mRNA and protein expression levels was examined,and the proliferative effect on H1299 cells was observed. Results Soy isoflavone crude extract and DD promoted proliferation and inhibited apoptosis of normal lung cells and inhibited proliferation and promoted apoptosis of lung cancer cells. p53 signaling pathway was significantly enriched in the DD-treated groupNES=1.78,P=0.000,and the expressions of p53 and CASP9 genes were found to be significantly up-regulated in the treated group. Compared with the control group,mRNA expression of CASP9 and p53 significantly increased in both HELF and H1299 cells treated with DDP<0.05,and p53 protein expression also increased in HELF cellsP<0.05. After inhibition of p53 expression,DD significantly increased the mRNA expression of p53 in H1299 and HELF cellsP<0.05 and also markedly increased the expression of p53 protein in H1299 cellsP<0.05,and it was observed that DD inhibited the proliferation of lung cancer cells. Conclusions DD inhibits the proliferation and promotes the apoptosis of lung cancer H1299 cells,and the mechanism mainly involves the p53 signaling pathway.
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A representative condensation of acrylonitrile and aryl acetonitrile has been reported for the synthesis of α-amino-ß-cyano cyclohexene. The reaction was carried out mildly in an open environment at room temperature. The scope and versatility of the method have been demonstrated with 20 examples, containing highly active ethynyl groups. Further applications for 4-aminopyrimidine compounds were performed. A mechanism was proposed, involving Michael additions between acrylonitrile and aryl acetonitriles as well as intramolecular condensation.
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In order to understand the interspecific and ecological relationships of Michelia odora (extremely small population) community and strengthen the protection of wild M. odora resources in Junzifeng Nature Reserve, we studied the niche characteristics and interspecific associations of dominant tree species. The results showed that M. odora, Machilus chekiangensis, Schima superba, and Alniphyllum fortunei had obvious niche breadth advantages, which were the constructive species of the community. Among the 190 groups of species pairs among the 20 dominant tree species, 50.5% of species pairs had niche overlap value greater than 0.5. The degree of ecological niche differentiation among species was general. M. odora had large niche overlap with other 19 species, indicating a competitive risk when resources were insufficient. The overall associations of dominant tree species were significantly positive, indicating the community was at the late stage of relatively stable succession. The results ofχ2 test, asso-ciation coefficient, and Pearson correlation coefficient showed that all the significance ratios of interspecific association were lower, and that the independence among species was relatively strong. There was a positive correlation between interspecific association and niche overlap. The M. odora community was relatively mature, with full utilization of resources and stable interspecific relationship. To promote the rejuvenation and create a good habitat of M. odora population, the population size with large overlap with M. odora niche and significant negative association could be appropriately limited, while that with positive interaction could be increased.
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Magnoliaceae , Theaceae , Árboles , Ecosistema , Densidad de PoblaciónRESUMEN
We present a novel optical coherence elastography (OCE) method to characterize mechanical hysteresis of soft tissues based on transient (milliseconds), low-pressure (<20â Pa) non-contact microliter air-pulse stimulation and micrometer-scale sample displacements. The energy dissipation rate (sample hysteresis) was quantified for soft-tissue phantoms (0.8% to 2.0% agar) and beef shank samples under different loading forces and displacement amplitudes. Sample hysteresis was defined as the loss ratio (hysteresis loop area divided by the total loading energy). The loss ratio was primarily driven by the sample unloading response which decreased as loading energy increased. Samples were distinguishable based on their loss ratio responses as a function loading energy or displacement amplitude. Finite element analysis and mechanical testing methods were used to validate these observations. We further performed the OCE measurements on a beef shank tissue sample to distinguish the muscle and connective tissue components based on the displacement and hysteresis features. This novel, noninvasive OCE approach has the potential to differentiate soft tissues by quantifying their viscoelasticity using micron-scale transient tissue displacement dynamics. Focal tissue hysteresis measurements could provide additional clinically useful metrics for guiding disease diagnosis and tissue treatment responses.
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Cellular barriers such as the cell membranes, lysosomes or nuclear pores of tumor cells hinder the drugs delivery and weaken the efficiency of traditional tumor therapies. Targeted destructing tumor cell membranes can quickly destroy cell homeostasis and kill cells without facing intracellular delivery barriers. Herein, we designed a self-delivery phototherapeutic chimeric peptide (CCP) for high efficient cell membrane-targeting combinational low-temperature photothermal therapy (LTPTT) and photodynamic therapy (PDT). The self-assembled CCP nanoparticles display remarkable tumor accumulation after systemic administration without additional carriers, avoiding the carriers related side toxicities. The CCPs are able to generate reactive oxygen species (ROS) and mild heat (<45 °C) locally at cell membrane and quickly induce immunogenic cell death to achieve efficient combinational LTPTT/PDT. The damage-associated molecular patterns released after cell membrane rupture effectively elicit antitumor immunity to eradicate residual tumor cells. With a single dosage and short-term near-infrared (NIR) light irradiation, CCPs significantly inhibit growth and metastasis of tumor, and prolong survival time of tumor-bearing mice. This work presents a unique cell membrane-targeting phototherapy strategy to kill tumor and suppress metastasis in an effective, safe and minimally invasive manner.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Animales , Línea Celular Tumoral , Membrana Celular , Ratones , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Péptidos/uso terapéutico , Fototerapia , TemperaturaRESUMEN
Downregulation of adenosine triphosphate (ATP)-dependent heat shock proteins (HSPs) can significantly reduce the tumorigenicity of cancer cells and overcome heat endurance to achieve high-performance mild temperature (≤45 °C) photothermal therapy (PTT). Herein, we designed and constructed 4T1 cancer cell membrane-coated, lonidamine (LN)-loaded and DL-menthol (DLM)-loaded hollow mesoporous Prussian blue nanoparticles (PBLM@CCM NPs). DLM with mild phase change characteristics served as a plugging agent to avoid early leakage and allow thermally controllable release of LN, which enabled selective intracellular delivery of LN to reduce the HSPs and overcome the heat endurance in PTT by inhibiting the generation of intracellular ATP. The biocompatible PBLM@CCM NPs with good tumor targeting efficiency achieved high-efficiency mild temperature PTT. Meanwhile, PBLM@CCM NPs could allow photoacoustic (PA) imaging and generate heat to promote the phase change of DLM for ultrasound (US) imaging, which is of great value for future clinical translational studies.
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Hipertermia Inducida , Nanopartículas , Neoplasias , Adenosina Trifosfato , Biomimética , Línea Celular Tumoral , Humanos , Hipertermia Inducida/métodos , Imagen Multimodal , Nanopartículas/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Fototerapia/métodos , Terapia Fototérmica , TemperaturaRESUMEN
Background: Whether women have a higher risk of adverse events compared with men following coronary angiography (CAG) and percutaneous coronary intervention (PCI) remains controversial. We aimed to investigate the sex differences in characteristics, treatments and outcomes among patients undergoing CAG and PCI in a large Chinese cohort. Methods: We analyzed patients undergoing CAG and/or PCI in this multi-center registry cohort study Cardiorenal ImprovemeNt II (CIN-II) in 5 Chinese tertiary hospitals from 2007 to 2020. Clinical characteristics, treatment (discharge medication and PCI) and in-hospital outcomes (mortality and major bleeding) were compared between women and men. Results: Totally 141,459 patients underwent CAG (44,362 [31.4%] women), of which 69,345 patients underwent PCI (15,376 [22.2%] women). Women were older (64.4 vs. 60.8 years), had more chronic comorbidities and lower PCI rate for stable coronary artery disease (CAD) than men (52.8 vs. 64.2%). Women received less CAG and PCI procedures. Among women undergoing PCI they received similar discharge medication treatment. In addition, women undergoing PCI had mildly lower rate of major bleeding (0.2 vs. 0.3%, P = 0.033) but higher in-hospital mortality (1.2 vs. 0.8%, P < 0.001). After adjustment, women had a higher risk in the major bleeding (adjusted odds ratio, 2.04 [95% CI: 1.07 to 3.62]), and the in-hospital mortality (adjusted odds ratio, 1.87 [95% CI: 1.36 to 2.56]). Conclusion: Among our Chinese cohort, women are older with more chronic comorbidities, receiving less PCI procedure and similar discharge medication treatment. Women have nearly 90% higher risk of in-hospital mortality and over 1-fold increased risk of major bleeding after PCI compared with men.
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Analysis of corneal tissue natural frequency was recently proposed as a biomarker for corneal biomechanics and has been performed using high-resolution optical coherence tomography (OCT)-based elastography (OCE). However, it remains unknown whether natural frequency analysis can resolve local variations in tissue structure. We measured heterogeneous samples to evaluate the correspondence between natural frequency distributions and regional structural variations. Sub-micrometer sample oscillations were induced point-wise by microliter air pulses (60-85 Pa, 3 ms) and detected correspondingly at each point using a 1,300 nm spectral domain common path OCT system with 0.44 nm phase detection sensitivity. The resulting oscillation frequency features were analyzed via fast Fourier transform and natural frequency was characterized using a single degree of freedom (SDOF) model. Oscillation features at each measurement point showed a complex frequency response with multiple frequency components that corresponded with global structural features; while the variation of frequency magnitude at each location reflected the local sample features. Silicone blocks (255.1 ± 11.0 Hz and 249.0 ± 4.6 Hz) embedded in an agar base (355.6 ± 0.8 Hz and 361.3 ± 5.5 Hz) were clearly distinguishable by natural frequency. In a beef shank sample, central fat and connective tissues had lower natural frequencies (91.7 ± 58.2 Hz) than muscle tissue (left side: 252.6 ± 52.3 Hz; right side: 161.5 ± 35.8 Hz). As a first step, we have shown the possibility of natural frequency OCE methods to characterize global and local features of heterogeneous samples. This method can provide additional information on corneal properties, complementary to current clinical biomechanical assessments, and could become a useful tool for clinical detection of ocular disease and evaluation of medical or surgical treatment outcomes.
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The instinctive protective stress responses of tumor cells hamper low-temperature photothermal therapy (LTPTT), resulting in tumor recurrence and metastasis. The rapid blood clearance and low-efficiency tumor enrichment of nanomedicines also decrease the efficacy of LTPTT. In this study, we fabricated coassembled photothermal agents (indocyanine green, ICG) and autophagy inhibitors (chloroquine, CQ) and red blood cell and cancer cell hybrid membrane (RCm)-camouflaged ICGCQ@RCm nanoparticles (ICGCQ@RCm NPs) to enhance tumor LTPTT. The ICGCQ@RCm NPs exhibited prolonged blood drug circulation and markedly enhanced drug accumulation in tumor tissues. The ICGCQ@RCm NPs reduced the thermal tolerance of tumor cells to sensitize ICG-mediated LTPTT by inhibiting protective autophagy. The ICGCQ@RCm NPs exerted strong immunogenic cell death (ICD) after efficient LTPTT to activate antitumor immunity. In addition, ICGCQ@RCms optimized the therapeutic efficacy by imaging-guided LTPTT, taking advantage of the near-infrared (NIR) fluorescence of ICG. Consequently, the ICGCQ@RCm NPs effectively inhibited tumors under mild LTPTT, significantly suppressed tumor metastasis and prolonged the survival time of tumor-bearing mice. Furthermore, the ICGCQ@RCm NPs showed high biosafety in vitro and in vivo. The ICGCQ@RCm NPs demonstrated tumor-targeting and imaging-guided autophagy inhibition-sensitized LTPTT using two Food and Drug Administration (FDA)-approved drugs, which have great potential for clinical application.
Asunto(s)
Hipertermia Inducida , Nanopartículas , Animales , Autofagia , Biomimética , Línea Celular Tumoral , Hipertermia Inducida/métodos , Ratones , Nanopartículas/uso terapéutico , Terapia FototérmicaRESUMEN
BACKGROUND: The clinical signs, symptoms, and the etiology of sensitive skin (SS) in general populations have been extensively studied over the last decades, but the characteristics of SS in Xinjiang, particularly the age-related characteristics, still remain unknown. OBJECTIVE: This study aimed to characterize the SS facial skin in normal adolescents of Xinjiang. METHODS: A questionnaire was developed based on SS and given to each participant. The clinical signs, symptoms, associated trigger factors, and DQLI of facial SS were compared in normal young Chinese males versus females. RESULTS: A total of 3584 freshmen were investigated, wherein 83 were diagnoses as self-reported facial SS (2.3%). The prevalence of SS was found to be significantly higher in females than in males. Spicy food, mood change, and skin care products are the major contributors to facial SS (p < 0.01). Moreover, family history and sun exposure are closely related to the onset of SS (p < 0.05). More SS patients were sensitive to emotional factors and had a greater difficulty with shopping or housework, dressing, socializing, or other leisure activities. The main manifestations of SS are flushing, erythema, and dry skin on buccal, frontal, and temporal sputum. The symptoms mainly include skin burning and dry itching, and two or more symptoms at the same time. The absolute value of red area and pores of SS were higher than that of normal skin (p < 0.05). CONCLUSIONS: The prevalence, symptoms, clinical characteristics, and triggering factors of facial SS in normal young of Xinjiang, especially freshmen in the 17-21 age group, were not similar with SS, which might be due to racial and regional differences.