Anti-angiogenesis agents plus chemoradiotherapy for locally advanced nasopharyngeal cancer: a systematic review and meta-analysis.

PURPOSE: To evaluate literature evidences about the efficacy and safety of anti-angiogenesis agents plus chemoradiotherapy versus chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma. METHODS: The relevant literature was systematically searched from the date of establishment to April 2023 in PubMed, Embase, Web of Science, The Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biological Medicine, Wanfang and VIP database. Search terms included: Nasopharyngeal Neoplasms, Angiogenesis inhibitors, Endostar, Anlotinib, Apatinib, Bevacizumab, Sunitinib, Pazopanib, Chemoradiotherapy. The literature was strictly screened according to the inclusion and exclusion criteria, and 8 eligible studies were finally included in our meta-analysis (4 randomized controlled trials and 4 retrospective studies). RESULTS: A total of 642 patients were included, with 316 in the anti-angiogenesis agents plus chemoradiotherapy group and 326 in the chemoradiotherapy group. The results of our meta-analysis showed that compared with chemoradiotherapy group, the complete response rate (RR = 1.35, 95% CI 1.05-1.74, P = 0.02), objective response rate (RR = 1.26, 95% CI 1.12-1.43, P = 0.0002) in the anti-angiogenesis agents plus chemoradiotherapy group were significantly improved. In terms of safety, there was a higher incidence of cardiac arrhythmia (RR = 3.63, 95% CI 1.16-11.37, P = 0.03) and hypertension (RR = 1.85, 95% CI 1.04-3.27, P = 0.004) in the anti-angiogenesis agents plus chemoradiotherapy group, while no statistically significant differences were reported in other adverse reactions (all P > 0.05). CONCLUSION: Compared with chemoradiotherapy, anti-angiogenesis agents plus chemoradiotherapy could bring more benefits in terms of short-term efficacy, particularly by notably improving both complete response rate and objective response rate, and overall adverse reactions were acceptable. Anti-angiogenesis agents plus chemoradiotherapy may provide a promising direction for the treatment of locally advanced nasopharyngeal carcinoma. SYSTEMATIC REVIEW REGISTRATION: https://inplasy.com/inplasy-2023-8-0076/ , registration number INPLASY202380076.

Cannabidiol protects against acute aortic dissection by inhibiting macrophage infiltration and PMAIP1-induced vascular smooth muscle cell apoptosis.

Acute aortic dissection (AAD) progresses rapidly and is associated with high mortality; therefore, there remains an urgent need for pharmacological agents that can protect against AAD. Herein, we examined the therapeutic effects of cannabidiol (CBD) in AAD by establishing a suitable mouse model. In addition, we performed human AAD single-cell RNA sequencing and mouse AAD bulk RNA sequencing to elucidate the potential underlying mechanism of CBD. Pathological assays and in vitro studies were performed to verify the results of the bioinformatic analysis and explore the pharmacological function of CBD. In a ß-aminopropionitrile (BAPN)-induced AAD mouse model, CBD reduced AAD-associated morbidity and mortality, alleviated abnormal enlargement of the ascending aorta and aortic arch, and suppressed macrophage infiltration and vascular smooth muscle cell (VSMC) apoptosis. Bioinformatic analysis revealed that the pro-apoptotic gene PMAIP1 was highly expressed in human and mouse AAD samples, and CBD could inhibit Pmaip1 expression in AAD mice. Using human aortic VSMCs (HAVSMCs) co-cultured with M1 macrophages, we revealed that CBD alleviated HAVSMCs mitochondrial-dependent apoptosis by suppressing the BAPN-induced overexpression of PMAIP1 in M1 macrophages. PMAIP1 potentially mediates HAVSMCs apoptosis by regulating Bax and Bcl2 expression. Accordingly, CBD reduced AAD-associated morbidity and mortality and mitigated the progression of AAD in a mouse model. The CBD-induced effects were potentially mediated by suppressing macrophage infiltration and PMAIP1 (primarily expressed in macrophages)-induced VSMC apoptosis. Our findings offer novel insights into M1 macrophages and HAVSMCs interaction during AAD progression, highlighting the potential of CBD as a therapeutic candidate for AAD treatment.

Research progress in the management of vascular disease with cannabidiol: a review.

The morbidity and mortality rates associated with vascular disease (VD) have been gradually increasing. Currently, the most common treatment for VD is surgery, with the progress in drug therapy remaining slow. Cannabidiol (CBD) is a natural extract of Cannabis sativa L. with sedative, analgesic, and nonaddictive properties. CBD binds to 56 cardiovascular-related receptors and exerts extensive regulatory effects on the cardiovascular system, making it a potential pharmacological agent for the management of VD. However, most CBD studies have focused on neurological and cardiac diseases, and research on the management of VD with CBD is still rare. In this review, we summarize the currently available data on CBD in the management of VD, addressing four aspects: the major molecular targets of CBD in VD management, pharmacokinetic properties, therapeutic effects of CBD on common VDs, and side effects. The findings indicate that CBD has anti-anxiety, anti-oxidation, and anti-inflammatory properties and can inhibit abnormal proliferation and apoptosis of vascular smooth muscle and endothelial cells; these effects suggest CBD as a therapeutic agent for atherosclerosis, stress-induced hypertension, diabetes-related vasculopathy, ischemia-reperfusion injury, and vascular damage caused by smoking and alcohol abuse. This study provides a theoretical basis for further research on CBD in the management of VD.

Roles of Immune and Oxidative Stress-Related Factors in the Diagnosis of Coronary Artery Disease: A Retrospective Study.

BACKGROUND: Coronary artery disease (CAD) is one of the main causes of sudden death, but its exact pathogenesis requires further study. Thus, this study aimed to explore the immune and oxidative stress-related factors in CAD progression and their roles in CAD diagnosis. METHODS: Bioinformatics analysis was used in this study, and the GSE23561 dataset (training set) we used contained the transcriptome sequencing results of six CAD peripheral blood samples and nine control samples. The data were obtained and analysed by querying the Gene Expression Omnibus database. First, the differentially expressed immune and oxidative stress-related genes (DEIOGs) between the groups were identified. DEIOGs were then analysed based on Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. A protein-protein interaction (PPI) network for DEIOGs was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database, and hub genes were identified through the PPI network. Moreover, transcription factors and microRNAs (miRNAs) targeting hub genes were identified to explore the potential regulatory mechanisms of hub genes. The receiver operating characteristic (ROC) curve analysis was constructed to examine the role of hub genes in CAD diagnosis. Finally, the data of GSE23561 (validated set) were used to validate the diagnostic potential of these hub genes. RESULTS: Primarily, 66 DEIOGs were identified, which are involved in many important pathways related to CAD, such as the "mitogen-activated protein kinase (MAPK) signalling pathway" and "lipid and atherosclerosis". A PPI network of DEIOGs was then constructed, and 10 hub genes were identified sequentially. A total of 37 transcription factors and 481 miRNAs that played important roles in hub genes regulation were identified. The ROC curves indicated that five special hub genes (Fos, Il6, Jun, Mapk3, and Mmp9) could serve as potential diagnostic biomarkers for CAD. CONCLUSIONS: Bioinformatics analysis technology was used to identify 10 hub DEIOGs that might play a crucial role in CAD progression, and five special hub genes (Fos, Il6, Jun, Mapk3, and Mmp9) could be regarded as potential biomarkers for CAD diagnosis. However, further studies are required to verify the functions of these hub genes.

Minimal Invasive Removal of Leukotrichia and Hair Transplantation: A Two-step Surgery in the Treatment of Stable Follicular Vitiligo.

BACKGROUND: Follicular vitiligo is a distinct subtype of vitiligo characterized by the selective destruction of the follicular melanocytic reservoir. The treatment of follicular vitiligo-associated leukotrichia has always been a clinical challenge. METHODS: Twenty participants with stable follicular vitiligo were recruited between 2020 to 2021 and accepted two-stage surgery. In stage one, an incision around the vitiligo lesion was performed to subcutaneously dissect and scrape the leukotrichia. In stage two, healthy follicles obtained from the occipital donor site were transplanted into the vitiligo area. Follow-up examinations were conducted for a year postoperatively by the camera and dermatoscope to observe the growth state, the color and the surviving number of the transplanted hairs. Besides, the satisfaction of the patients was recorded to evaluate the potential surgical improvement. RESULTS: Twenty patients with stable follicular vitiligo underwent two-stage surgery and their mean age was 29 years old. The transplanted hair grew with natural texture as expected. The average survival rate of the transplanted hair follicles was 93.8%. No recurrence of leukotrichia showed up in the recipient area. No complications were observed and the postoperative scars in the recipient area were entirely covered by black hair. All patients were satisfied with the resulting cosmetic appearance. CONCLUSIONS: Minimally invasive removal of leukotrichia combined with hair transplantation might be an appropriate surgical option for stable follicular vitiligo to create natural and stable pigmented hair.

Blood Supply of the Temporal Flap Pedicled With Orbicularis Oculi Muscle: Anatomy and Its Clinical Implications.

BACKGROUND: Traumatic injury or tumor resection can lead to eyelid defects, nasal defects, and cheek defects. The temporal flap pedicled with orbicularis oculi muscle (OOM) can be used to repair these defects. This cadaver-based anatomic study aimed to evaluate the blood supply of this flap and investigate its clinical implications. METHODS: Twenty hemifaces from 10 cadavers were used in this study. The number of arteries supplying OOM of the flap, the diameter of the artery entering OOM, and the maximum width of OOM were recorded. All data were presented as mean±SD values and analyzed using Student t -test. A P value<0.05 was considered statistically significant. RESULTS: Of these 10 specimens, 7 were males and 3 were females. The average age was 67.7 years (range, 53-78 y). The number of arteries supplying OOM was 8.5±1.4 in the male and 7.8±1.2 in the female. The diameter of the zygomatico-orbital artery was detected as 0.53±0.06 mm in the male and 0.40±0.11 mm in the female. The maximum width of OOM was detected as 2.5±0.1 cm in the male and 2.2±0.1 cm in the female. Males had significantly larger average values than females in the diameter of zygomatico-orbital artery and maximum width of OOM ( P =0.012, P <0.001, respectively). However, the number of arteries supplying OOM did not differ significantly between sex ( P =0.322). CONCLUSIONS: We conclude that the blood supply of the temporal flap pedicled with OOM is abundant and reliable. The findings provide surgeons with valuable anatomic knowledge for repairing facial defects with this flap.

Development, External Validation, and Visualization of Machine Learning Models for Predicting Occurrence of Acute Kidney Injury after Cardiac Surgery.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major complication that results in short- and long-term mortality among patients. Here, we adopted machine learning algorithms to build prediction models with the overarching goal of identifying patients who are at a high risk of such unfavorable kidney outcomes. Methods: A total of 1686 patients (development cohort) and 422 patients (validation cohort), with 126 pre- and intra-operative variables, were recruited from the First Medical Centre and the Sixth Medical Centre of Chinese PLA General Hospital in Beijing, China, respectively. Analyses were performed using six machine learning techniques, namely K-nearest neighbor, logistic regression, decision tree, random forest (RF), support vector machine, and neural network, and the APPROACH score, a previously established risk score for CSA-AKI. For model tuning, optimal hyperparameter was achieved by using GridSearch with 5-fold cross-validation from the scikit-learn library. Model performance was externally assessed via the receiver operating characteristic (ROC) and decision curve analysis (DCA). Explainable machine learning was performed using the Python SHapley Additive exPlanation (SHAP) package and Seaborn library, which allow the calculation of marginal contributory SHAP value. Results: 637 patients (30.2%) developed CSA-AKI within seven days after surgery. In the external validation, the RF classifier exhibited the best performance among the six machine learning techniques, as shown by the ROC curve and DCA, while the traditional APPROACH risk score showed a relatively poor performance. Further analysis found no specific causative factor contributing to the development of CSA-AKI; rather, the development of CSA-AKI appeared to be a complex process resulting from a complex interplay of multiple risk factors. The SHAP summary plot illustrated the positive or negative contribution of RF-top 20 variables and extrapolated risk of developing CSA-AKI at individual levels. The Seaborn library showed the effect of each single feature on the model output of the RF prediction. Conclusions: Efficient machine learning approaches were successfully established to predict patients with a high probability of developing acute kidney injury after cardiac surgery. These findings are expected to help clinicians to optimize treatment strategies and minimize postoperative complications. Clinical Trial Registration: The study protocol was registered at the ClinicalTrials Registration System (https://www.clinicaltrials.gov/, #NCT04966598) on July 26, 2021.

RNA methylation in vascular disease: a systematic review.

Despite the rise in morbidity and mortality associated with vascular diseases, the underlying pathophysiological molecular mechanisms are still unclear. RNA N6-methyladenosine modification, as the most common cellular mechanism of RNA regulation, participates in a variety of biological functions and plays an important role in epigenetics. A large amount of evidence shows that RNA N6-methyladenosine modifications play a key role in the morbidity caused by vascular diseases. Further research on the relationship between RNA N6-methyladenosine modifications and vascular diseases is necessary to understand disease mechanisms at the gene level and to provide new tools for diagnosis and treatment. In this study, we summarize the currently available data on RNA N6-methyladenosine modifications in vascular diseases, addressing four aspects: the cellular regulatory system of N6-methyladenosine methylation, N6-methyladenosine modifications in risk factors for vascular disease, N6-methyladenosine modifications in vascular diseases, and techniques for the detection of N6-methyladenosine-methylated RNA.

Nimotuzumab combined with chemoradiotherapy for the treatment of cervical cancer: A meta-analysis of randomized controlled trials.

Objectives: To assess the clinical efficacy and toxicity of nimotuzumab in combination with chemoradiotherapy or chemoradiotherapy alone in the treatment of cervical cancer. Methods: The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biomedical Medicine, Wanfang, and VIP databases were systematically searched for relevant literature. Ultimately, six randomised controlled trials (n=393) were included in our meta-analysis. Results: A total of 393 patients were included, of which 197 were in the nimotuzumab combined with chemoradiotherapy group and 196 were in the chemoradiotherapy group. The results of our meta-analysis showed that the complete remission rate (risk ratio [RR] = 1.34, 95% confidence interval [CI]: 1.08-1.65, P = 0.007), objective response rate (RR = 1.30, 95% CI: 1.16-1.44, P < 0.05), and three-year survival rate (RR = 1.27, 95% CI: 1.06-1.51, P = 0.008) in the nimotuzumab combined with chemoradiotherapy group were significantly improved compared with the chemoradiotherapy group. This difference was not statistically significant when comparing the incidence of adverse reactions (such as leukocytopenia, gastrointestinal reaction, radiocystitis, and radioproctitis) between the two groups. Conclusions: Nimotuzumab in combination with chemoradiotherapy has some advantages over chemoradiotherapy alone in the treatment of cervical cancer and does not increase toxicity. Therefore, nimotuzumab has the potential to be an effective treatment for cervical cancer; however, further evidence from large-scale randomised controlled trials is needed.

Astaxanthin attenuates irradiation-induced osteoporosis in mice by inhibiting oxidative stress, osteocyte senescence, and SASP.

Radiation therapy (RT) is a crucial part of many treatment plans for cancer patients. However, major undesired side effects are associated with this treatment, including impaired bone remodeling and bone loss. Irradiation induces bone loss due to promoted osteoclastic bone resorption and reduced osteoblastic bone formation. Astaxanthin (AST) is a natural antioxidant with anti-oxidative and anti-aging properties. However, it is unclear whether AST is also protective against osteoporosis induced by ionizing radiation (IR). Here, we evaluate the efficacy of AST in mitigating IR-induced bone loss in a mouse model where both hindlimbs received radiation. Reduced BMD, bone biomechanical strength, bone formation, elevated oxidative stress, and osteoclast activity with microarchitectural deterioration of trabecular and cortical bones were observed in IR mice. Supplementation with AST corrected these osteoporotic phenotypes, caused by IR, by inhibiting oxidative stress, DNA damage, osteocyte senescence, and senescence-associated secretory phenotype (SASP), subsequently promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption. The results from our study provide experimental evidence for the clinical use of AST to prevent IR-induced osteoporosis in cancer patients.

The synergistic mechanism of fibroblast growth factor 18 and integrin ß1 in rat abdominal aortic aneurysm repair.

BACKGROUND: Abdominal aortic aneurysms have a high mortality rate. While surgery is the preferred treatment method, the biological repair of abdominal aortic aneurysms is being increasingly studied. We performed cellular and animal experiments to investigate the simultaneous function and mechanism of fibroblast growth factor 18 and integrin ß1 in the biological repair of abdominal aortic aneurysms. METHODS: Endothelial and smooth muscle cells of rat arteries were used for the cellular experiments. Intracellular integrin ß1 expression was regulated through lentiviral transfection. Interventions with fibroblast growth factor 18 were determined according to the experimental protocol. Several methods were used to detect the expression of elastic fiber component proteins, cell proliferation, and migratory activity of endothelial and smooth muscle cells after different treatments. For animal experiments, abdominal aortic aneurysms were induced in rats by wrapping the abdominal aortae in sterile cotton balls soaked with CaCl2 solution. Fibroblast growth factor 18 was administered through tail vein injections. The local expression of integrin ß1 was regulated through lentiviral injections into the adventitia of the abdominal aortic aneurysms. The abdominal aortae were harvested for pathological examinations and tensile mechanical tests. RESULTS: The expression of integrin ß1 in endothelial and smooth muscle cells could be regulated effectively through lentiviral transfection. Animal and cellular experiments showed that fibroblast growth factor 18 + integrin ß1 could improve the expression of elastic fiber component proteins and enhance the migratory and proliferative activities of smooth muscle and endothelial cells. Moreover, animal experiments showed that fibroblast growth factor 18 + integrin ß1 could enhance the aortic integrity to withstand stretch of aortic aneurysm tissue. CONCLUSION: Fibroblast growth factor 18 + integrin ß1 improved the biological repair of abdominal aortic aneurysms in rats by increasing the expression of elastic proteins, improving the migratory and proliferative abilities of endothelial and smooth muscle cells, and improving aortic remodeling.

Short-term results of percutaneous closure of a patent foramen ovale guided by transoesophageal echocardiography in patients with cryptogenic stroke: a retrospective study.

BACKGROUND: A patent foramen ovale (PFO) is a risk factor for cryptogenic stroke (CS), and interventional therapy for PFO can reduce the recurrence rate of CS. However, interventional therapies are primarily guided by X-ray imaging, and data on regular post-surgical follow-up with the transthoracic ultrasound foaming test (UFT) are rare. Thus, this study aimed to assess the short-term (12 months) results of PFO occlusion guided by transoesophageal echocardiography (TEE) and the results of regular UFTs. METHODS: Clinical records, echocardiographic data, and UFT results of 75 patients who underwent interventional therapy for PFO and CS were retrospectively analysed. The patients were grouped according to their preoperative UFT results: group A (n = 21), small volume of right-to-left shunts; group B (n = 22), moderate volume of right-to-left shunts; and group C (n = 32), large volume of right-to-left shunts. All patients were treated with an Amplatzer occluder under TEE guidance. UFT follow-up was conducted regularly until 12 months after surgery. RESULTS: No significant differences in preoperative data, length of hospital stay, or operative time were noted between the groups (p > 0.05). The length of the PFO and diameter of the occluder differed between the groups as follows: group A = group B < group C (p < 0.001). Notably, 1 patient in group C developed recurrent stroke 11 months postoperatively, and 2 patients in group C developed atrial arrhythmia, which improved after 3 months of antiarrhythmic treatment. However, 19 patients still had positive UFT results 12 months postoperatively. Furthermore, the positive UFT rate 12 months postoperatively differed between the groups as follows: group A = group B < group C (p < 0.05). A preoperative large-volume shunt was negatively associated with a negative UFT rate 12 months postoperatively (OR = 0.255, 95% CI: 0.104-0.625). CONCLUSIONS: In patients with PFO and CS, interventional therapy guided by TEE could lead to satisfactory short-term (12 months) outcomes. Although the positive UFT rate gradually decreased, some patients still had positive UFT results 12 months postoperatively. Preoperatively, a large volume of right-to-left shunts and a longer PFO were the two risk factors for positive UFT results postoperatively. Further studies are required to clarify the relationship between postoperative positive UFT results and stroke recurrence.

Magnetic Resonance Imaging Segmentation on the Basis of Boundary Tracking Algorithm in Lung Cancer Surgery.

This work was to study the guiding value of magnetic resonance imaging (MRI) based on the target region boundary tracking algorithm in lung cancer surgery. In this study, the traditional boundary tracking algorithm was optimized, and the target neighborhood point boundary tracking method was proposed. The iterative method was used to binarize the lung MRI image, which was applied to the MRI images of 50 lung cancer patients in hospital. The patients were divided into two groups as the progression-free survival (PFS) and overall survival (OS) of surgical treatment group (experimental group, n = 25) and nonsurgical treatment group (control group, n = 25). The experimental group received surgical resection, while the control group received systemic chemotherapy. The results showed that the traditional boundary tracking algorithm needed to manually rejudge whether the concave and convex parts of the image were missing. The target boundary tracking algorithm can effectively avoid the leakage of concave and convex parts and accurately locate the target image contour, fast operation, without manual intervention. The PFS time of the experimental group (325 days) was significantly higher than that of the control group (186 days) (P < 0.05). The OS time of the experimental group (697 days) was significantly higher than that of the control group (428 days) (P < 0.05). Fisher exact probability method was used to test the total survival time of patients in the two groups, and the tumor classification and treatment group had significant influence on the OS time (P < 0.05). The target boundary tracking algorithm in this study can effectively locate the contour of the target image, and the operation speed was fast. Surgical resection of lung cancer can improve the PFS and OS of patients.

Dihydrotestosterone-induced hair regrowth inhibition by activating androgen receptor in C57BL6 mice simulates androgenetic alopecia.

Androgenic alopecia (AGA), also known as male pattern baldness, is one of the most common hair loss diseases worldwide. The main treatments of AGA include hair transplant surgery, oral medicines, and LDL laser irradiation, although no treatment to date can fully cure this disease. Animal models play important roles in the exploration of potential mechanisms of disease development and in assessing novel treatments. The present study describes androgen receptor (AR) in C57BL/6 mouse hair follicles that can be activated by dihydrotestosterone (DHT) and translocate to the nucleus. This led to the design of a mouse model of androgen-induced AGA in vivo and in vitro. DHT was found to induce early hair regression, hair miniaturization, hair density loss, and changes in hair morphology in male C57BL/6 mice. These effects of DHT could be partly reversed by the AR antagonist bicalutamide. DHT had similar effects in an ex vivo model of hair loss. Evaluation of histology, organ culture, and protein expression could explain the mechanism by which DHT delayed hair regrowth.

Proposed mechanisms of low-level light therapy in the treatment of androgenetic alopecia.

Androgenetic alopecia (AGA) is a global challenge, affecting a large number of people worldwide. Efficacy of the existed treatments can barely meet the demands of patients. Patients who are poorly responding to those treatments are seeking for a more effective and suitable technique to treat their disease. Low-level light therapy (LLLT) is a newly developed technique, which has been proved to stimulate hair growth. Based on the function principle of LLLT in other domains and refer to the published literatures, we write this review to neaten and elucidate the possible mechanism of LLLT in the treatment of AGA. A review of published literature which is associated with keywords LLLT, photobiomodulation, AGA, treatment, hair growth, and mechanism was performed to elucidate the proposed mechanism of LLLT in the treatment of AGA. The present study shows that LLLT can accelerate hair growth in AGA patients. The proposed mechanism of LLLT in treating AGA may vary among different specialists. But we can summarize the consensual mechanisms as follows; low-level light absorbed by chromophores can lead to the production of nitric oxide (NO) and the modulation of reactive oxygen species (ROS). These mobilized molecules subsequently activate redox-related signaling pathways in hair follicle cells and perifollicular cells. Finally, these activated cells participate in the regrowth of hair follicle. Even though the efficacy of LLLT in the treatment of AGA in both men and women has already been confirmed, the present studies focusing on discovering LLLT are still inadequate and unsystematic. More studies are needed to standardize the optimum treatment parameters applied in promoting hair growth and determine the long-term safety and efficacy of LLLT. Current recognitions about the mechanisms of LLLT, mainly focused on the molecules that may take effect, neglected different cellular components that are functional in the hair follicle macro-environment.

Neutrophils mediated multistage nanoparticle delivery for prompting tumor photothermal therapy.

BACKGROUND: Neutrophil-based drug delivery system possesses excellent advantages in targeting at tumour because neutrophils are easily recruited by chemotactic factor in tumor microenvironment. Herein, we developed a novel tactic of multistage neutrophils-based nanoparticle delivery system for promoting photothermal therapy (PTT) of lung cancer. RESULTS: Au nanorod (AuNR) was successfully modified with bovine serum albumin (AuNRB) and further conjugated with RGD (AuNRBR), followed by neutrophil internalisation to obtain neutrophils-based delivery system (AuNRBR/N). The engineered neutrophils efficiently migrated across the epithelial cells due to inflammatory signal. They exhibited better toxicity against Lewis cells with laser irradiation in vitro. Moreover, AuNRBR/N showed significantly more targetability to tumour tissue compared with cell carrier-free AuNRBR, as demonstrated in Lewis tumour-bearing mice. The enhanced tumour homing efficiency of AuNRBR/N together with subsequently released AuNRBR from the neutrophils was favourable for further deep tissue diffusion and contributed to the inhibition of the tumour growth in PTT and improved survival rate (over 120 days). CONCLUSIONS: Overall results illustrated that the design of cell-based nanoparticle delivery system for PTT of cancer is promising.

Short-term results of interventional therapy for infants (7-36 months old) with patent ductus arteriosus and moderate-to-severe pulmonary hypertension: a retrospective study.

BACKGROUND: Patent ductus arteriosus (PDA) is a common congenital heart disease. Interventional therapy is an important treatment for PDA. Nevertheless, few studies have investigated the safety and effectiveness of interventional therapy for infants (age, 0-36 months) with PDA and moderate-to-severe pulmonary hypertension. Therefore, this study aimed to analyze the short-term (6 months) results and interventional therapy experience for infants with PDA and moderate-to-severe pulmonary hypertension. METHODS: Clinical records, echocardiographic data, and angiocardiography data of 28 infants (age, 7-36 months) who underwent interventional therapy for PDA and moderate-to-severe pulmonary hypertension between December 2011 and January 2017 at our hospital were retrospectively analyzed. All infants were treated using an Amplatzer occluder with local and deep sedation anesthesia under radiographic guidance. RESULTS: Infants with PDA and moderate-to-severe pulmonary hypertension had poor growth. Trace residual shunts were found in two infants immediately after procedure; both had disappeared by 6 months after procedure. No significant interventional therapy-related complications occurred in the other cases. Pulmonary systolic pressure, left atrial dimension, and left ventricular end-diastolic dimension immediately after interventional therapy and 6 months later were lower than the preoperative levels (P < 0.05). The left atrial and left ventricular end-diastolic dimensions at 6 months after interventional therapy were smaller than those immediately after interventional therapy (P < 0.05). Pulmonary systolic pressure rates immediately after interventional therapy and 6 months later were not significantly different (P = 0.505). Moreover, there were no significant differences in the left ventricular ejection fraction before, immediately after, and at 6 months after interventional therapy (P = 0.628). CONCLUSIONS: For infants (age, 7-36 months) with PDA and moderate-to-severe pulmonary hypertension, interventional therapy can achieve excellent immediate and short-term (6 months) results with careful preoperative evaluations, strict operative procedures, and careful follow-up.

Treatment with soluble bone morphogenetic protein type 1A receptor fusion protein alleviates irradiation-induced bone loss in mice through increased bone formation and reduced bone resorption.

An increased fracture risk is often observed in cancer patients undergoing radiotherapy (RT), particularly at sites within the field of radiation. Therefore, the development of appropriate therapeutic options to prevent RT-induced bone loss is urgently needed. A soluble form of the BMP receptor type 1A fusion protein (mBMPR1A-mFc) serves as an antagonist to endogenous BMPR1A. Previous studies have shown that mBMPR1A-mFc treatment increases bone mass in both ovary-intact and ovariectomized via promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption. The present study was designed to investigate whether mBMPR1A-mFc administration prevents radiation-induced bone deterioration in mice. We constructed an animal model of radiation-induced osteoporosis by exposure to a 2-Gy dose of X-rays. Micro-CT, histomorphometric, bone-turnover, and mechanical analyses showed that mBMPR1A-mFc administration prevented trabecular microarchitecture deterioration after RT because of a marked increase in bone formation and a decrease in bone resorption. Mechanistic studies indicated that mBMPR1A-mFc administration promoted osteoblastogenesis by activating Wnt/Lrp5/ß-catenin signaling while decreasing osteoclastogenesis by inhibiting the RANKL/RANK/OPG pathway. Our novel findings provide solid evidence for the application of mBMPR1A-mFc as a therapeutic treatment for radiation-induced osteoporosis.

Short-term results of bilateral internal mammary arterial grafting for patients aged 60-75 years - a retrospective study.

BACKGROUND: Bilateral internal mammary artery (BIMA) grafting has a good long-term survival rate and graft patency rate, but it is only recommended in young patients due to its high technical requirements and high incidence of sternal complications. Previous studies indicated that BIMA grafting has a significant benefit in patients aged 50-59 years, but this benefit does not extend to patients aged > 60 years. Thus, this study was designed to analyse the immediate artery graft function, short-term (3 months) results, and experience in preventing sternal complications for BIMA grafting in elderly patients (60-75 years old). METHODS: Clinical records and echocardiographic and coronary artery computed tomography angiography data of 155 patients who underwent BIMA grafting for coronary artery disease between 2015 and 2017 in our hospital were analysed retrospectively to summarise the operative experience and short-term (3 months) results. Patients were divided into two groups: Group A (n = 95), aged < 60 years and Group B (n = 60), aged 60-75 years. The operation time, aortic clamp time, and cardiopulmonary bypass time of these two groups were compared to analyse the operation difficulty and the flow and pulsatility index were compared to analyse the immediate artery graft function. The left ventricular end-diastolic dimension (LVEDD) and left ventricular ejection fraction (LVEF) of these two groups were compared to analyse heart function. RESULTS: There were no significant differences in the operation time, aortic clamp time, and cardiopulmonary bypass time as well as the flow and pulsatility index between these two groups (P > 0.05). There was no significant difference in the incidence of sternal wound complications, graft occlusion, and other common complications 3 months post-BIMA grafting between these two groups (P > 0.05). Furthermore, there was no significant difference in LVEDD and LVEF between the groups 3 months post-operation (P > 0.05). CONCLUSIONS: BIMA grafting was safe and effective for older patients (60-75 years). Similar to younger patients (< 60 years), BIMA grafting in elderly patients (60-75 years) can also achieve a satisfactory short-term (3 months) result. Thus, advanced age (60-75 years) should not be a contraindication for BIMA grafting.

Comparison of modified total leaflet preservation, posterior leaflet preservation, and no leaflet preservation techniques in mitral valve replacement - a retrospective study.

BACKGROUND: Mitral valve replacement with the total leaflet preservation technique can yield good results; however, its development is limited by patient-valve mismatch. Therefore, we compared the efficacies of the modified total leaflet preservation technique, posterior leaflet preservation technique, and no leaflet preservation technique in mitral valve replacement. METHODS: Clinical records and echocardiographic data of 180 patients who underwent mitral valve replacement for rheumatic mitral valve disease between 2009 and 2017 were analysed retrospectively to summarise the operative experience and short-term (six months) results. The patients were divided into three groups: group A (n = 62), treated with the modified total leaflet preservation technique; group B (n = 80), treated with the posterior leaflet preservation technique; and group C (n = 38), treated with the no leaflet preservation technique. RESULTS: No significant difference in the preoperative clinical data was noted between the groups (p > 0.05). The clamp and recovery times of group A were longer (p < 0.05) and shorter (p < 0.05), respectively, than those of groups B and C. The postoperative left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left ventricular ejection fraction of group A were significantly better than those of groups B and C. The incidence of low cardiac output syndrome in group A was lower than that in group C (p < 0.05). There was no postoperative left ventricular posterior wall rupture or mechanical valve dysfunction in group A. CONCLUSIONS: The short-term results of the modified total leaflet preservation technique were better than those of the other techniques. This technique is also suitable for patients with rheumatic mitral valve stenosis.