[Risk Factors and a Prediction Model for Frequent Acute Exacerbations of Chronic Obstructive Pulmonary Disease].

Objective To identify the risk factors of patients with frequent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and construct a prediction model based on the clinical data,providing a theoretical basis for the clinical prevention and treatment. Methods A total of 25 638 COPD patients admitted to the Department of Respiratory and Critical Care Medicine,the Third People's Hospital of Chengdu from January 1,2013 to May 1,2023 were selected.Among them,11 315 patients were included according to the inclusion and exclusion criteria,and their clinical characteristics were analyzed.Multivariate Logistic regression was carried out to identify the risk factors for frequent AECOPD.A nomogram model was utilized to quantify the risk of acute exacerbation,and the performance of the prediction model was assessed based on the area under the receiver operating characteristic (ROC) curve. Results In the patients with frequent AECOPD,male percentage (P<0.001),age (P<0.001),urban residence (P<0.001),smoking (P<0.001),length of stay (P<0.001),total cost (P<0.001),antibiotic cost (P<0.001),diabetes (P=0.003),respiratory failure (P<0.001),heart disease (P<0.001),application of systemic glucocorticoids (P<0.001),white blood cell count (P<0.001),neutrophil percentage (P<0.001),C-reactive protein (P<0.001),total cholesterol (P<0.001),and brain natriuretic peptide (BNP) (P<0.001) were all higher than those in the patients with infrequent AECOPD.Multivariate Logistic regression analysis revealed that age,urban residence,smoking,diabetes,heart disease,Pseudomonas aeruginosa infection,application of systemic glucocorticoids,antibiotics,respiratory failure,and elevated white blood cell count,total cholesterol,and BNP were independent risk factors for hospitalization due to frequent AECOPD.A nomogram model of hospitalization due to frequent AECOPD was constructed according to risk factors.The ROC curve was established to evaluate the performance of the model,which showed the area under the ROC curve of 0.899 (95%CI=0.892-0.905),the sensitivity of 85.30%,and the specificity of 79.80%. Conclusion Frequent AECOPD is associated with smoking,heart disease,application of systemic glucocorticoids,Pseudomonas aeruginosa infection,age,low body mass index,and elevated BNP.Predicting the risks of hospitalization due to frequent AECOPD by the established model can provide theoretical support for the treatment and risk factor management of the patients.

Clinical and pathological analyses of 14 cases of angiomatoid fibrous histiocytoma.

Angiomatoid fibrous histiocytoma (AFH) is a soft tissue tumor of uncertain differentiation. Although its prognosis is good, its diagnosis and differential diagnosis remain a challenge, particularly for tumors with an atypical morphology. We evaluated the clinicopathological characteristics of 14 AFH cases and examined the key factors in its diagnosis or differential diagnosis. The cohort comprised 6 men and 8 women aged 9-65 years (average age: 31.2 years). Most of the tumors (11/14, 79%) were located in soft tissues, whereas 3/14 (21%) were located in the lung (1 case) and brain (2 cases). Tumor cells were spindle-shaped to epithelioid, with a visible fibrous capsule (9/14, 64%), hemorrhagic gap (9/14, 64%), lymphocyte sleeve (7/14, 50%), necrosis (3/14, 21%), and infiltrative boundary (4/14, 29%). The tumors expressed desmin (10/14, 71%) and exhibited low levels of Ki-67. 13 cases (93%) displayed ESWSR1 gene rearrangement. At follow-up, 1 case (7%) experienced local tumor recurrence. AFH is a rare intermediate tumor. Its pathological diagnosis requires a comprehensive analysis of histological, immunophenotypic, and molecular genetic features to avoid misdiagnosis. Our study has further enriched the histological features of AFH, emphasizing the importance of differential diagnosis and providing a reference for clinical practice.

Osthole, an ingredient from Cnidium monnieri, reduces the pyroptosis and apoptosis in bronchial epithelial cells.

Osthole is the prominent active ingredient isolated from Cnidium. The role of osthole in chronic obstructive pulmonary disease (COPD) was investigated herein. Bronchial epithelial 16HBE cells were exposed to cigarette smoke extract (CSE) to generate injury models. The concentration of CSE had an inverse correlation with cell viability. Osthole suppressed inflammation, oxidative stress, apoptosis, and pyroptosis in 16HBE cells, along with a decrease in RIPK2 level. RIPK2 overexpression reversed the effects of osthole on the abovementioned aspects. This study found that the osthole could reduce RIPK2 level, inhibit pyroptosis, and alleviate the damage in 16HBE cells under CSE stimulation.

Evaluated expression of CELSR3 in oral squamous cell carcinoma is associated with perineural invasion and poor prognosis.

OBJECTIVE: The objective of this study was to evaluate CELSR3 expression and explore its potential mechanism in oral squamous cell carcinoma. STUDY DESIGN: CELSR3 mRNA expression was analyzed using The Cancer Genome Atlas (TCGA) database. CELSR3 protein expression in 135 surgical oral squamous cell carcinoma specimens was observed by immunohistochemical staining. Staining results were used to investigate the association between CELSR3 expression and clinicopathologic characteristics and prognosis. Bioinformatics analyses were used to explore the potential mechanism of CELSR3 in head and neck squamous cell carcinoma. RESULTS: CELSR3 mRNA expression was upregulated in patients with head and neck squamous cell carcinoma in the TCGA head and neck squamous cell carcinoma data set. Increased CELSR3 protein expression was associated with perineural invasion and poor clinical outcomes in patients with oral squamous cell carcinoma. Bioinformatics analyses revealed that CELSR3 is involvement in axonogenesis, neuron migration, and cell-cell adhesion, all of which are involved in the process of perineural invasion. CONCLUSION: CELSR3 may play a pro-oncogenic role in oral squamous cell carcinoma and can predict perineural invasion and poor survival. CELSR3 may be involved in oral squamous cell carcinoma progression by modulating perineural invasion.

Exosomal microRNA-15a from ACHN cells aggravates clear cell renal cell carcinoma via the BTG2/PI3K/AKT axis.

Accumulating studies have indicated that exosomal microRNAs (miRNAs/miRs) can mediate clear cell renal cell carcinoma (ccRCC) at the early stage, but the mechanisms remain to be specified. Here, we investigated the mechanism of exosomal miR-15a in ccRCC. After successful isolation of exosomes from RCC cells, we found that miR-15a was upregulated in ccRCC cells. Moreover, upregulation of miR-15a by pre-miR-15a promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition of ccRCC cells. A luciferase assay revealed that B-cell translocation gene 2 (BTG2) was a target gene of miR-15a and negatively correlated with miR-15a expression. BTG2 was poorly expressed in ccRCC, which reduced the proliferation of ccRCC cells. In addition, overexpression of BTG2 could reverse the promotive effects of miR-15a on ccRCC. Furthermore, BTG2 reduced PI3K/AKT pathway activity. Our results collectively indicated that exosomal miR-15a from RCC cells accelerated cell viability by downregulating BTG2 and promoting the activity of the PI3K/AKT signaling pathway. We demonstrated a novel mechanism by which exosomal miR-15a exerted pro-proliferatory effects on ccRCC, highlighting the potential of exosomal miR-15a as a target for ccRCC prognosis.

[Explore antioxidant quality markers of Hippophae tibetana based on "dry-method + wet-method" technology].

The cross combination of dry-method(network pharmacology analysis) and wet-method(high-resolution mass spectro-metry with antioxidation experiment) was used to predict antioxidant quality markers(Q-markers) of Hippophae tibetana. Ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) was developed to rapidly separate and identify the chemical constituents in H. tibetana. Then in DPPH free radicals and superoxide anion scavenging experiment, the antioxidant activity of the four different polar parts with extracts of petroleumether, ethyl acetate, n-butanol and water was evaluated. Network pharmacology method was used for functional enrichment and pathway analysis to screen antioxidant-related components and preliminarily explain the mechanism of action. On this basis, multi-source information was integrated to predict the antioxidant Q-markers. The results showed that 51 components in H. tibetana were identified, including 18 flavonoids, 14 terpenoids, 6 alkaloids, 4 coumarins and phenylpropanoids, 3 volatile components and 2 polyphenols. The antioxidant capacity of different fractions: ethyl acetate > n-butanol > water > petroleum ether. The medicine mainly acted on PI3 K-Akt and FoxO signaling pathways to perform antioxidant effects through flavonoids such as quercetin, luteolin and kaempferol. According to the results of dry-method and wet-method, quercetin, luteolin and kaempferol, the representatives of poly-hydroxy flavone, may be the antioxidant Q-markers of H. tibetana. In this study, with the antioxidant Q-markers of H. tibetana as an example, an investigation model of predicting Q-marker was discussed based on the ternary system of composition, function and informatics, providing a scientific basis for the establishment of quality evaluation standards for H. tibetana.

The Anatomy of the Temporal and Zygomatic Branches of the Facial Nerve: Application to Crow's Feet Wrinkles.

BACKGROUND: Advances in the understanding of wrinkling crow's feet while improving the safety and efficacy of botulinum toxin type A injection has pointed to drug dispersion in the lateral orbital wrinkles as a cause of adverse events of botulinum toxin type A injection. The purpose of this study is to identify the distribution of temporal and zygomatic branches of facial nerve in the orbicularis oculi muscles. METHODS: Anatomical dissection of cadavers was performed in 31 cadavers, 13 females and 18 males, with ages ranging from 20 to 60 years, which of all had been embalmed by 10% formalin solution. The facial nerve was identified within subcutaneous tissue close periorbital region and both traced proximal and distal. Its temporal branch, zygomatic branch, facial and muscular entrance were located and accurately measured relative to established surface landmarks. RESULTS: Dissection of the facial nerve revealed 2 to 6 entrances of the temporal branch into the orbicularis oculi and 1 to 5 entrances of the zygomatic branch into the orbicularis oculi. Concerning the measurements of neural entering points, distance and angle from orbicularis oculi muscle to lateral ocular angle, a distribution map of its muscular entrance and their patterns of distribution were constructed. According to the dense area of the coordinate map, there were 3 points determined as the muscular entrance points to established surface landmarks. CONCLUSIONS: An anatomical dissection of cadavers was performed to identify the distribution of temporal and zygomatic branches of the facial nerve in the orbicularis oculi. According to the dense area of the coordinate map, the surface landmarks of 3 points were established as the muscular entrance of the facial nerve (MEF).

Differences in the therapeutic effects of high-intensity focused ultrasound (HIFU) ablation on uterine fibroids with different shear wave velocity (SWV): a study of histopathological characteristics.

OBJECTIVE: To explore correlations between the therapeutic effect of high intensity focused ultrasound (HIFU) and histopathological characteristics of uterine fibroids with different Shear Wave Velocity (SWV) values. METHODS: A retrospective study was conducted on 36 women (43 fibroids) who had undergone high intensity focused ultrasound (HIFU) uterine fibroids ablation between January 2019 and January 2020. Preoperative fibroids tissue sections were obtained for histopathological examination. The pathological sections were stained with Masson-trichrome, and were observed and imaged under a Low-power microscope (4 × 10), while the smooth muscle cell (SMC) and collagen fiber content were semi-quantitatively measured. Preoperative fibroid SWV was measured using the Virtual Touch tissue quantification (VTQ) technique. Within one month after HIFU ablation, all patients had undergone a pelvic cavity MRI examination, which measured the size, volume, and non-perfused volume (NPV) of the fibroids. The formula: the ablation rate = NPV/target fibroid volume × 100% was used to calculate the ablation rate of the uterine fibroids. Correlation analysis of SWV values, HIFU ablation rate, along with the smooth muscle cell (SMC) and collagen fiber content, were conducted using the Spearman's correlation test. RESULTS: The collagen fiber and SMC content of the preoperative fibroids were 32.09 ± 15.90%/view and 37.61 ± 15.32%/view, respectively. Preoperative fibroid SWV value was 3.56 ± 0.71 m/s. Preoperative fibroid SWV was negatively correlated with SMC content (r = -0.445, p = 0.003), but positively correlated with collagen fiber content (r = 0.454, p = 0.002). The ablation rate was negatively correlated with collagen fiber content (r = -0.377, p = 0.013), but positively correlated with SMC content (r = 0.402, p = 0.007). CONCLUSION: Differences in histopathological characteristics may be important factors that induce differences in the therapeutic effects of HIFU ablation on uterine fibroids with different SWV values.

Gnaq Protects PC12 Cells from Oxidative Damage by Activation of Nrf2 and Inhibition of NF-kB.

Reactive oxygen species (ROS) are continuously produced as byproducts of aerobic metabolism. Oxidative stress (OS) plays an important role in the occurrence of several neurodegenerative diseases as well as aging because of the accumulation of ROS. Gnaq is a member of G protein α subunits. It has been reported that the expression level of Gnaq in the mouse forebrain cortex was significantly decreased with age in our previous study; therefore, we supposed that Gnaq contributes to attenuate the OS. In this study, we generated a Gnaq-overexpression cell using gene recombinant technique and lentivirus transfection technique in a neuron-like PC12 cell, and investigated whether Gnaq had antioxidant effects in PC12 cells treated with H2O2. The viability of cells, concentration of ROS, Nrf2 nuclear translocation, expression of antioxidant enzymes, activation of NF-κB and apoptosis were compared between Gnaq-PC12 cells and Vector-PC12 cells. Results showed that, compared with Vector-PC12 cells, the antioxidative ability of Gnaq-PC12 cells was significantly improved, while the ROS level in Gnaq-PC12 cells was significantly decreased. Nrf2 nuclear translocation was up-regulated and NF-κB nuclear translocation was down-regulated in Gnaq-PC12 cells after H2O2 treatment. The results suggest that Gnaq plays a crucial role in neuroprotection in PC12 cells. A possible mechanism for this would be that the overexpressed Gnaq enhances the antioxidative effect mediated by Nrf2 signal pathway and inhibits the cellular damaging effect through NF-κB signal pathway.

Design and synthesis of a vanadate-based ratiometric fluorescent probe for sequential recognition of Cu2+ ions and biothiols.

A novel YVO4:Eu3+@CDs core-shell nanomaterial with two main emission peaks at 405 and 617 nm was synthesized through a simple mixing method, in which the carbon quantum dots (CDs) self-assembled with the YVO4:Eu3+ nanoparticle, due to the high affinity of oxygen-containing groups such as -COOH or -OH of CDs to the metal ions on the surface of YVO4:Eu3+. The red fluorescence of YVO4:Eu3+@CDs located at 617 nm can be quenched by Cu2+ ions efficiently, while the blue emission remains invariable; based on this, we construct a ratio fluorescent probe YVO4:Eu3+@CDs for Cu2+ ion detection, in which the blue emission of CDs is selected as the reference signal, and the red emission of YVO4:Eu3+ acts as an output signal. Furthermore, the addition of biothiol recovers the quenched red fluorescence quickly, which can be completed in 18 minutes. Thus, YVO4:Eu3+@CDs can also be used as a 'turn on' ratio fluorescent probe for biothiol rapid detection. Taking l-cysteine (l-Cys) as the model, the fluorescence intensity of the 617 nm peak increases with increasing Cys, and the ratio of F617/F405 is linear to the concentration of Cys in the range of 0.1 µM to 10 µM with a detection limit of 41 nM. Compared with these single wavelength emission biothiol fluorescent probes, an obvious change in the fluorescence color from blue to pink can be conveniently observed by the naked eye under a UV lamp. Meanwhile, this ratiometric probe has also been demonstrated to be used for the visual identification of biothiols in real blood serum samples.

An anterior neurovascular interval approach to coronal shear fractures of the distal humerus: a prospective clinical study with short- to mid-term follow-up.

OBJECT: To explore the treatment effect of the anterior medial neurovascular interval approach to coronal shear fractures of the distal humerus. METHODS: This prospective study included two female patients who were 30-64 years old, with a mean age of 47 years. Fractures were caused by falling from a bicycle. The time between the injury and operation was 1-2 days, with a mean time interval of 1.5 days. Two patients with coronal shear fracture of the distal humerus were treated with open reduction and internal fixation using anterior neurovascular interval approach. RESULTS: There were no intraoperative and postoperative neurological and vascular complications or infections, and the fracture was united. At 12 months after the surgery, the patient returned to work without pain, and with a normal range of motion for elbow and forearm rotation. The X-rays revealed excellent fracture union, no signs of heterotopic ossification, and no traumatic arthritis. According to Mayo's evaluation standards for elbow function, a score of 100 is excellent. CONCLUSIONS: The application of the anterior neurovascular interval approach of the elbow in the treatment of shear fracture of the articular surface of the distal humerus, particularly the trochlea of the humerus, can reduce the stripping of the soft tissue.

An anterior neurovascular interval approach to coronal shear fractures of the distal humerus: a prospective clinical study with short- to mid-term follow-up

SUMMARY OBJECT: To explore the treatment effect of the anterior medial neurovascular interval approach to coronal shear fractures of the distal humerus. METHODS: This prospective study included two female patients who were 30-64 years old, with a mean age of 47 years. Fractures were caused by falling from a bicycle. The time between the injury and operation was 1-2 days, with a mean time interval of 1.5 days. Two patients with coronal shear fracture of the distal humerus were treated with open reduction and internal fixation using anterior neurovascular interval approach. RESULTS: There were no intraoperative and postoperative neurological and vascular complications or infections, and the fracture was united. At 12 months after the surgery, the patient returned to work without pain, and with a normal range of motion for elbow and forearm rotation. The X-rays revealed excellent fracture union, no signs of heterotopic ossification, and no traumatic arthritis. According to Mayo's evaluation standards for elbow function, a score of 100 is excellent. CONCLUSIONS: The application of the anterior neurovascular interval approach of the elbow in the treatment of shear fracture of the articular surface of the distal humerus, particularly the trochlea of the humerus, can reduce the stripping of the soft tissue.

RESUMO OBJETIVO: Explorar o efeito do tratamento com uma abordagem anterior do intervalo neurovascular médio para fraturas de cisalhamento coronal da porção distal do úmero. METODOLOGIA: Este estudo prospectivo incluiu duas pacientes do sexo feminino de 30-64 anos de idade, com idade média de 47 anos. As fraturas foram causadas por quedas de bicicleta. O tempo entre a lesão e a operação foi de 1-2 dias, com um intervalo de tempo médio de 1,5 dias. Duas pacientes com cisalhamento coronal da porção distal do úmero foram tratadas com redução aberta e fixação interna utilizando a abordagem anterior do intervalo neurovascular. RESULTADOS: Não houve complicações neurológicas e vasculares intra e pós-operatórias, nem complicações ou infecções, e a fratura foi unida. Após 12 meses da cirurgia, as pacientes retornaram ao trabalho sem dor e com uma amplitude normal de movimento de rotação do antebraço e cotovelo. Os raios-X revelaram excelente união das fraturas, sem sinais de ossificação heterotópica e sem artrite traumática. De acordo com as diretrizes da clínica Mayo para avaliação da função do cotovelo, uma pontuação de 100 é considerada excelente. CONCLUSÃO: A aplicação da abordagem anterior do intervalo neurovascular do cotovelo no tratamento de uma fratura de cisalhamento da superfície articular da porção distal do úmero, especificamente da tróclea do úmero, pode reduzir o desgaste do tecido mole.

Inhibition of autophagy enhances adenosine­induced apoptosis in human hepatoblastoma HepG2 cells.

In cancer research, autophagy acts as a double­edged sword: it increases cell viability or induces cell apoptosis depending upon the cell context and functional status. Recent studies have shown that adenosine (Ado) has cytotoxic effects in many tumors. However, the role of autophagy in Ado­induced apoptosis is still poorly understood. In the present study, Ado­induced apoptotic death and autophagy in hepatoblastoma HepG2 cells was investigated and the relationship between autophagy and apoptosis was identified. In the present study, it was demonstrated that Ado inhibited HepG2 cell growth in a time­ and concentration­dependent manner and activated endoplasmic reticulum (ER) stress, as indicated by G0/G1 cell cycle arrest, the increased mRNA and protein levels of GRP78/BiP, PERK, ATF4, CHOP, cleaved caspase­3, cytochrome c and the loss of mitochon-drial membrane potential (ΔΨm). Ado also induced autophagic flux, revealed by the increased expression of the autophagy marker microtubule­associated protein 1 light chain 3­II (LC3­II), Beclin­1, autophagosomes, and the degradation of p62, as revealed by western blot analysis and macrophage­derived chemokine (MDC) staining. Blocking autophagy using LY294002 notably entrenched Ado­induced growth inhibition and cell apoptosis, as demonstrated with the increased expression of cytochrome c and p62, and the decreased expression of LC3­II. Conversely, the autophagy inducer rapamycin alleviated Ado­induced apoptosis and markedly increased the ΔΨm. Moreover, knockdown of AMPK with si­AMPK partially abolished Ado­induced ULK1 activation and mTOR inhibition, and thus reinforced CHOP expression and Ado­induced apoptosis. These results indicated that Ado­induced ER stress resulted in apoptosis and autophagy concurrently. The AMPK/mTOR/ULK1 signaling pathway played a protective role in the apoptotic procession. Inhibition of autophagy may effectively enhance the anticancer effect of Ado in human hepatoblastoma HepG2 cells.

Combined transbronchoscopic needle aspiration (TBNA) and rapid on-site cytological evaluation (ROSE) for diagnosis of tuberculous mediastinal lymphadenitis: A case report.

INTRODUCTION: The diagnosis of tuberculous mediastinal lymphadenitis remains a challenge, and the use of transbronchoscopic needle aspiration (TBNA) combined with rapid on-site cytological evaluation (ROSE) is still unclear. A case of tuberculous mediastinal lymphadenitis was illustrated to show the diagnostic value of TBNA and ROSE. CASE PRESENTATION: In this case report, we presented a typical case of a 44-year-old male who underwent obvious odynophagia and mild symptom of dyspnea. One isolated mass positioned on posterior mediastinum was examined as positive discovery. Finally, he was diagnosed with tuberculous mediastinal lymphadenitis by using TBNA combined with ROSE and treated with anti-TB. CONCLUSIONS: TBNA is an efficacious and safe approach, which is worth popularizing for the clinical diagnosis of mediastinal masses. Meanwhile, ROSE is useful to reduce the numbers of needle passes during TBNA. We aimed to emphasize 2 key points in this case report. Firstly, a rare symptom of Tuberculosis in adults was supported by the patient. Secondly, TBNA combined with ROSE is useful for the diagnosis of tuberculous mediastinal lymphadenitis.

Src kinase inhibitor PP2 regulates the biological characteristics of A549 cells via the PI3K/Akt signaling pathway.

Lung cancer is one of the most prevalent types of cancer worldwide, with a poor prognosis for patients and a concomitant financial burden on society. There are a number of different pathological subtypes, with non-small cell lung cancer (NSCLC) being the primary subtype. Although anticancer therapy has led to a marked improvement in the survival rate of patients in recent years, the survival rate remains poor. Potential reasons for this include a lack of early diagnosis and drug resistance, which is considered to be associated with mutations in components of signaling pathways, tumor suppressors and epidermal growth factor receptor, and certain other complex mechanisms to a certain extent. It is therefore imperative to develop novel therapies. In the present study, the pyrazolopyrimidine compound PP2 was used to inhibit Src family protein tyrosine kinases in A549 cells. It was demonstrated that PP2 was able to suppress cell viability, migration and invasion, and promote apoptosis via regulating the phosphoinositide 3-kinase/protein kinase B/B-cell lymphoma 2/caspase-3 signaling pathway. PP2 may therefore be useful in anti-NSCLC therapy in the future.

Honokiol Inhibits Proliferation, Invasion and Induces Apoptosis Through Targeting Lyn Kinase in Human Lung Adenocarcinoma Cells.

Honokiol is a natural compound with small molecular structure and extracted from bark of magnolia trees. The biological activities of honokiol include anti-oxidation, anti-inflammation as well as anti-tumor. However, their mechanism remains unknown. In this study, A549 cell line and EGFR-mutant cell line PC-9 with higher expression level of Lyn than A549 cells were used to assess the anti-tumor effects of honokiol. As shown in this study, honokiol is an effective drug on inhibiting proliferation and inducing apoptosis depended on Lyn and EGFR signal pathway regulated by Lyn, and its efficacy is stronger in PC-9 cells than A549 cells. In addition, this anti-tumor effect in PC-9 cells was weakened by Lyn-knockdown. Taken together, this study indicated the mechanism of honokiol on lung adenocarcinoma and provides a possibility of honokiol as an effective anti-tumor medicine.

Supercritical Fluid-Assisted Fabrication of Indocyanine Green-Encapsulated Silk Fibroin Nanoparticles for Dual-Triggered Cancer Therapy.

Despite the success and advantages over traditional chemotherapeutic strategies, photothermal therapy (PTT) suffers from certain limitations, such as poor stability, low therapeutic efficacy of PTT agents in vivo, and their affinity loss during the multistep synthesis process of delivery carriers, among others. To address these limitations, we designed a stable, biocompatible, and dual-triggered formulation of indocyanine green (ICG)-encapsulated silk fibroin (SF) (ICG-SF) nanoparticles using supercritical fluid (SCF) technology. We demonstrated that ICG encapsulation in SF through this environmental-friendly approach has offered excellent photothermal stability, the pH-responsive release of ICG from SF specifically in the tumor acidic environment, and its substantial activation with near-infrared (NIR) light at 808 nm significantly enhanced the PTT efficiency. In vitro and in vivo photothermal experiments have shown that these ICG-SF nanoparticles were capable of devastating tumor cells merely under light-induced hyperthermia. Together, these results have suggested that the biocompatible ICG-SF nanoparticles prepared by the SCF process resulted in high PTT efficiency and may have a great potential as a delivery system for sustained cancer therapy.

Baicalin attenuates chronic hypoxia-induced pulmonary hypertension via adenosine A2A receptor-induced SDF-1/CXCR4/PI3K/AKT signaling.

BACKGROUND: Baicalin, an important flavonoid in Scutellaria baicalensis Georgi extracts, exerts a variety of pharmacological effects. In this study, we explored the effects of baicalin on chronic hypoxia-induced pulmonary arterial hypertension (PAH) and investigated the mechanism underlying these effects. Moreover, we examined whether the inflammatory response was mediated by the A2A receptor (A2AR) and stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)-induced phosphatidyl inositol-3-kinase (PI3K) signaling in vivo. METHODS: We established a hypoxia-induced pulmonary hypertension (HPH) mouse model by subjecting wild-type (WT) and A2AR knockout (A2AR-/-) animals to chronic hypoxia, and we examined the effects of a 4-week treatment with baicalin or the A2AR agonist CGS21680 in these animals. Invasive hemodynamic parameters, the right ventricular hypertrophy index, pulmonary congestion, the pulmonary arterial remodeling index, blood gas parameters, A2AR expression, and the expression of SDF-1/CXCR4/PI3K/protein kinase B (PKB; AKT) signaling components were measured. RESULTS: Compared with WT mice, A2AR-/- mice exhibited increased right ventricular systolic pressure (RVSP), right ventricle-to-left ventricle plus septum [RV/(LV + S)] ratio, RV weight-to-body weight (RV/BW) ratio, and lung wet weight-to-body weight (Lung/BW) ratio in the absence of an altered mean carotid arterial pressure (mCAP). These changes were accompanied by increases in pulmonary artery wall area and thickness and reductions in arterial oxygen pressure (PaO2) and hydrogen ion concentration (pH). In the HPH model, A2AR-/- mice displayed increased CXCR4, SDF-1, phospho-PI3K, and phospho-AKT expression compared with WT mice. Treating WT and A2AR-/- HPH mice with baicalin or CGS21680 attenuated the hypoxia-induced increases in RVSP, RV/(LV + S) and Lung/BW, as well as pulmonary arterial remodeling. Additionally, baicalin or CGS21680 alone could reverse the hypoxia-induced increases in CXCR4, SDF-1, phospho-PI3K, and phospho-AKT expression. Moreover, baicalin improved the hypoxemia induced by 4 weeks of hypoxia. Finally, we found that A2AR levels in WT lung tissue were enhanced by hypoxia and that baicalin up-regulated A2AR expression in WT hypoxic mice. CONCLUSIONS: Baicalin exerts protective effects against clinical HPH, which are partly mediated through enhanced A2AR activity and down-regulated SDF-1/CXCR4-induced PI3K/AKT signaling. Therefore, the A2AR may be a promising target for baicalin in treating HPH.

Amphiregulin Antibody and Reduction of Axial Elongation in Experimental Myopia.

To examine the mechanism of ocular axial elongation in myopia, guinea pigs (age: 2-3weeks) which either underwent unilateral or bilateral lens-induced myopization (group 1) or which were primarily myopic at baseline (group 2) received unilateral intraocular injections of amphiregulin antibody (doses: 5, 10, or 15µg) three times in intervals of 9days. A third group of emmetropic guinea pigs got intraocular unilateral injections of amphiregulin (doses: 0.25, 0.50 or 1.00ng, respectively). In each group, the contralateral eyes received intraocular injections of Ringer's solution. In intra-animal inter-eye comparison and intra-eye follow-up comparison in groups 1 and 2, the study eyes as compared to the contralateral eyes showed a dose-dependent reduction in axial elongation. In group 3, study eyes and control eyes did not differ significantly in axial elongation. Immunohistochemistry revealed amphiregulin labelling at the retinal pigment epithelium in eyes with lens-induced myopization and Ringer's solution injection, but not in eyes with amphiregulin antibody injection. Intraocular injections of amphiregulin-antibody led to a reduction of lens-induced axial myopic elongation and of the physiological eye enlargement in young guinea pigs. In contrast, intraocularly injected amphiregulin in a dose of ≤1ng did not show a significant effect. Amphiregulin may be one of several essential molecular factors for axial elongation.

Central Projection of Antennal Sensory Neurons in the Central Nervous System of the Mirid Bug Apolygus lucorum (Meyer-Dür).

The mirid bug Apolygus lucorum (Meyer-Dür), a polyphagous pest, is dependent on olfactory cues to locate various host plant species and mates. In this study, we traced the projection pathway of the antennal sensory neurons and visualized their projection patterns in the central nervous system of A. lucorum through confocal microscopy and digital reconstructions. We also examined the glomerular organization of the primary olfactory center of the brain, the antennal lobe, and created a three-dimensional model of the glomeruli. We found that the axons of the sensory neurons project into the brain via the ipsilateral antennal nerve, and descend further into the gnathal ganglion, prothoracic ganglion, mesothoracic ganglion, and metathoracic ganglion, and reach as far as to the abdominal ganglion. Such a projection pattern indicates that antennal sensory neurons of A. lucorum may be potentially directly connected to motor neurons. The antennal lobe, however, is the major target area of antennal sensory neurons. The antennal lobe is composed of a large number of glomeruli, i.e. 70-80 glomeruli in one AL of A. lucorum. The results of this study which provide information about the basic anatomical arrangement of the brain olfactory center of A. lucorum, are important for further investigations of chemosensory encoding mechanisms of the mirid bug.