Semiphysical Design Concept for Developing Miniaturized Microrobots In Vivo.

The miniaturization of biomedical microrobots is crucial for their in vivo applications. However, it is challenging to reduce their size while maintaining their biomedical functions. To resolve this contradiction, we propose a semiphysical design concept for developing miniaturized microrobots, in which invisible components such as light beams are utilized to replace most of the physical parts of a microrobot, thus minimizing its physical size without sacrificing its biomedical functions. According to this design, we have constructed a semiphysical microrobot (SPM) composed of main light beam, light-responsive microparticle, and auxiliary light beam, serving as the actuation system, recognition part, and surgical claws, respectively. Based on the functions of actuation, biosensing, and microsurgery, a SPM has been applied for a series of applications, including thrombus elimination at the branch vessel, stratified removal of multilayer thrombus, and biosensing-guided microsurgery. The proposed semiphysical design concept should bring new insight into the development of miniaturized biomedical microrobots.

Application of MFI-5 in severe complications and unfavorable outcomes after radical resection of colorectal cancer.

BACKGROUND: Frailty is considered a characteristic manifestation of physiological decline in multiple organ systems, which significantly increases the vulnerability of elderly individuals with colorectal cancer (CRC) and is associated with a poor prognosis. While studies have demonstrated that the 11-factor Modified Frailty Index (mFI-11) can effectively predict adverse outcomes following radical resection of CRC, there is a lack of research on the applicability of the 5-factor Modified Frailty Index (mFI-5) within this patient population. METHODS: In this retrospective analysis, we examined a cohort of CRC patients aged 65 years and above who had undergone radical resection. For each patient, we calculated their mFI-5 score, considering a score of ≥ 2 as an indication of frailty. We conducted univariate and multivariate analyses to assess the association between the mFI-5 and adverse outcomes as well as postoperative complications. RESULTS: Patients with an mFI-5 score ≥ 2 exhibited a significantly higher incidence of serious postoperative complications (53% vs. 30%; P = 0.001) and experienced a longer hospital stay [19.00 (15.00-24.50) vs. 17.00 (14.00-20.00); P < 0.05]. Notably, an mFI-5 score greater than 2 emerged as an independent risk factor for severe postoperative complications (odds ratio: 2.297; 95% confidence interval: 1.216 to 4.339; P = 0.01). Furthermore, the mFI-5 score displayed predictive capabilities for severe postoperative complications with an area under the receiver operating characteristic (ROC) curve of 0.629 (95% confidence interval: 0.551 to 0.707; P < 0.05). CONCLUSION: The mFI-5 demonstrates a high level of sensitivity in predicting serious complications, prolonged hospital stays, and mortality following radical resection of colorectal carcinoma. As a practical clinical assessment tool, the mFI-5 enables the identification of high-risk patients and facilitates preoperative optimization.

Anlotinib vs placebo as third- or further-line treatment for patients with small cell lung cancer: a randomised, double-blind, placebo-controlled Phase 2 study.

BACKGROUND: This study aimed to evaluate the efficacy and safety of anlotinib as a third-line and subsequent treatment for patients with small cell lung cancer (SCLC). METHODS: We conducted this Phase 2 trial at 11 institutions in China. Patients with pathologically confirmed SCLC who failed at least two lines of chemotherapy were enrolled. Subjects were randomly assigned in a 2:1 ratio to receive either anlotinib 12 mg orally once daily for 14 days every 3 weeks or placebo. The primary endpoint was progression-free survival (PFS). RESULTS: Between March 30, 2017 and June 8, 2018, a total of 82 and 38 patients were randomly assigned to receive anlotinib and placebo. The median PFS was significantly longer in the anlotinib group compared with the placebo group (4.1 months [95% confidence interval (CI), 2.8-4.2] vs 0.7 months [95% CI, 0.7-0.8]; hazard ratio (HR) 0.19 [95% CI, 0.12-0.32], p < 0.0001). Overall survival (OS) was significantly longer with anlotinib than placebo (7.3 months [95% CI, 6.1-10.3] vs 4.9 months [95% CI, 2.7-6.0]; HR 0.53 [95% CI, 0.34-0.81], p = 0.0029). CONCLUSIONS: Anlotinib as a third-line or subsequent treatment for Chinese patients with SCLC showed improved PFS and OS than placebo with favourable safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT03059797.

Effect of intraocular anti-VEGF on cystoid macular edema associated with Henoch-Schonlein purpura-a case report.

BACKGROUND: To report a bilateral cystoid macular edema associated with Henoch-Schonleinpurpura. CASE PRESENTATION: A 21-year-old man presented a bilateral, painless, and bilateral blurred vision for 5 weeks with visual acuity (VA) of 6/12 on the right eye and 6/48 on the left. FA and OCT showed bilateral cystoid macular edema, and the fundus photograph showed retinal hemorrhages. Using intravenous dexamethasone could reduce macular edema, but it reoccurred shortly after switching to oral prednisone. Repeated intraocular injection of anti-VEGF in both eyes was performed and VA improved to 6/6 on the right eye and 6/7.5 on the left with the regression of edema after 6 months follow-up. CONCLUSIONS: Intraocular anti-VEGF might be an alternative choice to glucocorticoid in cases of bilateral cystoid macular edema associated with Henoch-Schonlein purpura.

FNDC3B circular RNA promotes the migration and invasion of gastric cancer cells via the regulation of E-cadherin and CD44 expression.

Circular RNAs (circRNAs) are a new class of RNAs, and many studies have identified thousands of circRNAs in tumor cells. Fibronectin type III domain-containing protein 3B (FNDC3B) circular RNA (circFNDC3B, circBase ID: hsa_circ_0006156) circularizes with exons 5 and 6. Gibson Assembly DNA technology was used to construct a circFNDC3B expression vector without a splice site and restriction enzyme site. We showed that circFNDC3B increased migration and invasion in gastric cancer (GC). Ectopic expression of circFNDC3B reduced the level of E-cadherin protein to promote the epithelial-mesenchymal transition in GC. RNA immunoprecipitation assays and RNA pull-down assays confirmed that circFNC3B increased CD44 expression, which was associated with cell adhesion, via the formation of a ternary complex of circFNDC3B-IGF2BP3-CD44 mRNA. These results indicated that circFNDC3B was associated with the degree of malignancy to highlight the specific characteristics of cell invasion.

GMDS knockdown impairs cell proliferation and survival in human lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is the most common type of lung cancer and one of the most lethal and prevalent cancers. Aberrant glycosylation was common and essential in tumorigenesis, with fucosylation as one of the most common types disrupted in cancers. However, it is still unknown whether genes involved in fucosylation are important for lung adenocarcinoma development and process. METHODS: GMDS is involved in cellular fucosylation. Here we examined GMDS expression level at both mRNA and protein level in lung adenocarcinoma. The impact of GMDS knockdown on lung adenocarcinoma in vitro and in vivo was investigated. Transcriptome changes with GMDS knockdown in lung adenocarcinoma cells were also examined to provide insights into related molecular mechanisms. RESULTS: GMDS expression is significantly upregulated in lung adenocarcinoma at both mRNA and protein levels. Lentivirus-mediated shRNA strategy inhibited GMDS expression efficiently in human lung adenocarcinoma cells A549 and H1299, and GMDS knockdown impaired cell proliferation, colony formation ability, induced cell cycle arrest, and apoptosis in both cell lines. Furthermore, GMDS knockdown inhibited tumorigenesis in a xenograft mice model of lung adenocarcinoma. Microarray analysis explored the GMDS-mediated molecular network and revealed that the CASP8-CDKN1A axis might be critical for lung adenocarcinoma development. CONCLUSIONS: These findings suggest that GMDS upregulation is critical for cell proliferation and survival in human lung adenocarcinoma and might serve as a potential biomarker for lung adenocarcinoma diagnosis and treatment.

Occurrence of oral Candida colonization and its risk factors among patients with malignancies in China.

OBJECTIVES: Oral colonization of Candida could lead to later development of oropharyngeal candidiasis or candidemia among the immunocompromised patients. This study aims to describe the occurrence and risk factors of oral Candida colonization in patients with malignancies. MATERIALS AND METHODS: From October 2012 to March 2013, 78 patients with pulmonary cancer (group I), 101 patients with gastrointestinal tract tumor (group II), 79 patients with hematopoietic system malignant tumor (group III), and 101 healthy controls were consecutively recruited in a hospital in Beijing, China. The oral rinse samples were taken and Candida species were identified; the enzymes activities were tested. RESULTS: In total, 110 and 27 Candida strains were isolated from 91 patients and 26 controls, respectively. The oral colonization rate with Candida albicans in group III (12.7 %) was significant lower than that in group I (30.8 %), group II (33.7 %), and control group (25.7 %). The oral colonization rates with non-albicans Candida species in group I, group II, and group III were 15.4, 10.9, and 12.7 %, respectively, while only one non-albicans Candida strain was identified in control group. The non-albicans Candida species exhibited a lower virulence than C. albicans. Age was an independent risk factor for Candida colonization in patients with pulmonary cancer and digestive tract malignant tumor, "Teeth brush <1 time/day" was an independent risk factor for Candida colonization in patients with hematopoietic system tumor. CONCLUSIONS: The differences of risk factors for oral Candida colonization in patients with different cancers require different strategies for the prevention and control of Candida infection. CLINICAL RELEVANCE: Old aged patients with pulmonary cancer and digestive tract malignant tumor are high-risk population for Candida colonization. Increasing frequency of teeth brush might be helpful for preventing Candida colonization.

Discovering a New Drug Against Acute Kidney Injury by Using a Tailored Photoacoustic Imaging Probe.

Acute kidney injury (AKI) has become an increasing concern for patients due to the widespread clinical use of nephrotoxic drugs. Currently, the early diagnosis of AKI is still challenging and the available therapeutic drugs cannot meet the clinical demand. Herein, this work has investigated the key redox couple involved in AKI and develops a tailored photoacoustic (PA) imaging probe (AB-DiOH) which can reversibly respond to hypochlorite (ClO-)/glutathione (GSH) with high specificity and sensitivity. This probe enables the real-time monitoring of AKI by noninvasive PA imaging, with better detection sensitivity than the blood test. Furthermore, this probe is utilized for screening nephroprotective drugs among natural products. For the first time, astragalin is discovered to be a potential new drug for the treatment of AKI. After oral administration, astragalin can be efficiently absorbed by the animal body, alleviate kidney injury, and meanwhile induce no damage to other normal tissues. The treatment mechanism of astragalin has also been revealed to be the simultaneous inhibition of oxidative stress, ferroptosis, and cuproposis. The developed PA imaging probe and the discovered drug candidate provide a promising new tool and strategy for the early diagnosis and effective treatment of AKI.

Fully Active Delivery of Nanodrugs In Vivo via Remote Optical Manipulation.

The active delivery of nanodrugs has been a bottleneck problem in nanomedicine. While modification of nanodrugs with targeting agents can enhance their retention at the lesion location, the transportation of nanodrugs in the circulation system is still a passive process. The navigation of nanodrugs with external forces such as magnetic field has been shown to be effective for active delivery, but the existing techniques are limited to specific materials like magnetic nanoparticles. In this study, an alternative actuation method is proposed based on optical manipulation for remote navigation of nanodrugs in vivo, which is compatible with most of the common drug carriers and exhibits significantly higher manipulation precision. By the programmable scanning of the laser beam, the motion trajectory and velocity of the nanodrugs can be precisely controlled in real time, making it possible for intelligent drug delivery, such as inverse-flow transportation, selective entry into specific vascular branch, and dynamic circumvention across obstacles. In addition, the controlled mass delivery of nanodrugs can be realized through indirect actuation by the microflow field. The developed optical manipulation method provides a new solution for the active delivery of nanodrugs, with promising potential for the treatment of blood diseases such as leukemia and thrombosis.

An increase in SNHG5 expression is associated with poor cancer prognosis, according to a meta-analysis.

BACKGROUND: He long noncoding RNA small nucleolar host RNA 5 (SNHG5) is highly expressed in many cancers, and there is a notable correlation between the elevated expression of SNHG5 and survival outcome in cancer patients. The objective of this study was to conduct a meta-analysis to evaluate the correlation between SNHG5 expression and the clinical outcome of cancer patients. METHODS: Six relevant electronic databases were exhaustively searched, and, depending on the inclusion and exclusion criteria, appropriate literature was obtained. The Newcastle-Ottawa Scale (NOS) score was utilized to evaluate the quality of the research for every article included, and pertinent data from each study were carefully extracted. Hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were combined to explore the association of SNHG5 expression levels with cancer prognosis, and sensitivity analyses and assessments of publication bias were also conducted to investigate any possibility in the publication of the studies. RESULTS: Eleven studies encompassing 721 patients were ultimately collected. When combined, the hazard ratios (HRs) revealed a substantial direct correlation between elevated SNHG5 expression and an unfavourable prognosis for cancer patients (HR = 1.90, 95% CI 0.87-4.15); however, the correlation did not reach statistical significance. Furthermore, high SNHG5 expression was predictive of advanced TNM stage (OR: 1.988, 95% CI 1.205-3.278) and larger tumour size (OR: 1.571, 95% CI 1.090-2.264); moreover, there were nonsignificant relationships between SNHG5 expression and DM (OR: 0.449, 95% CI 0.077-2.630), lymph node metastasis (OR: 1.443, 95% CI 0.709-2.939), histological grade (OR: 2.098, 95% CI 0.910-4.838), depth of invasion (OR: 1.106, 95% CI 0.376-3.248), age (OR: 0.946, 95% CI 0.718-1.247) and sex (OR: 0.762, 95% CI 0.521-1.115). CONCLUSION: SNHG5 expression is typically increased in the majority of tumour tissues. Elevated SNHG5 expression may indicate poor prognosis in cancer patients. Therefore, SNHG5 is a promising potential therapeutic target for tumours and a reliable prognostic biomarker.

High expression of serine protease 2 (PRSS2) associated with invasion, metastasis, and proliferation in gastric cancer.

BACKGROUND: Accumulating evidence indicates that the occurrence and development of tumors are related to the activation of oncogenes and the inactivation of tumor suppressor genes caused by epigenetic mechanisms. However, the function of serine protease 2 (PRSS2) in gastric cancer (GC) is still unknown. Our study aimed to find a regulation network involved in GC. METHODS: The mRNA data (GSE158662 and GSE194261) of GC and normal tissues were downloaded from the Gene Expression Omnibus (GEO) dataset. Differential expression analysis was performed using R software, and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted by using Xiantao software. Besides, we used Quantitative Real-time PCR (qPCR) to verify our conclusions. After gene knockdown, cell migration and CCK-8 experiment were carried out to detect the effect of gene on cell proliferation and invasion. RESULTS: Totally, 412 differentially expressed genes (DEGs) were identified from GSE158662 and 94 DEGs were identified from GSE196261. Km-plot database results indicated that PRSS2 exhibited high diagnosis worth for GC. Gene functional annotation enrichment analysis revealed that these hub mRNAs were mainly taken part in the process of tumorigenesis and development. Besides, vitro experiments showed that down-regulation of PRSS2 gene reduced the proliferation and invasion ability of GC cells. CONCLUSIONS: Our results indicated that PRSS2 may play vital roles in the carcinogenesis and progression of GC and can be potential biomarkers for patients with GC.

Nanoindentation Study of Calcium-Silicate-Hydrate Gel via Molecular Dynamics Simulations.

The mechanical properties of calcium-silicate-hydrate (C-S-H) gels in cementitious materials are mainly realized by nanoindentation experiments. There is limited research on the dynamic response of the molecular structure of C-S-H under nanoindentation conditions. This study simulated the nanoindentation on the C-S-H gel samples by the molecular dynamics method considering the essential factors of modeling and loading process. The results demonstrate that the averaged elastic moduli we obtained had slight differences from those by experiments. In contrast to the experimental results, the gels showed bi-modulus and transverse isotropic with the material principal direction perpendicular to the C-S-H layers. The modulus in a direction increased with the loading speed, which indicates that C-S-H behaves viscous due to the water motion in the sample and the propagation of stress wave. The saturation of water influenced the moduli differently because more water in C-S-H will reduce the polymerization of silicon chains and then weaken the local stiffness. The conclusions provide a deeper understanding of the mechanism on the unique mechanical response of C-S-H gels.

Optically Programmable Living Microrouter in Vivo.

With high reconfigurability and swarming intelligence, programmable medical micromachines (PMMs) represent a revolution in microrobots for executing complex coordinated tasks, especially for dynamic routing of various targets along their respective routes. However, it is difficult to achieve a biocompatible implantation into the body due to their exogenous building blocks. Herein, a living microrouter based on an organic integration of endogenous red blood cells (RBCs), programmable scanning optical tweezers and flexible optofluidic strategy is reported. By harvesting energy from a designed optical force landscape, five RBCs are optically rotated in a controlled velocity and direction, under which, a specific actuation flow is achieved to exert the well-defined hydrodynamic forces on various biological targets, thus enabling a selective routing by integrating three successive functions, i.e., dynamic input, inner processing, and controlled output. Benefited from the optofluidic manipulation, various blood cells, such as the platelets and white blood cells, are transported toward the damaged vessel and cell debris for the dynamic hemostasis and targeted clearance, respectively. Moreover, the microrouter enables a precise transport of nanodrugs for active and targeted delivery in a large quantity. The proposed RBC microrouter might provide a biocompatible medical platform for cell separation, drug delivery, and immunotherapy.

Dynamic monitoring of circulating tumor DNA to analyze genetic characteristics and resistance profile of lorlatinib in ALK positive previously treated NSCLC.

BACKGROUND: To dynamically monitor the changes of genomic characteristics during lorlatinib treatment and analyze the resistance profile of lorlatinib in ALK-positive advanced Chinese patients with non-small cell lung cancer (NSCLC) with first- and second-generation ALK inhibitor resistance. METHODS: Ten eligible patients who were from a phase 2 study in China and admitted to the Fifth Medical Center of PLA General Hospital were analyzed. Blood samples were collected for next-generation sequencing (NGS) to characterize genetic variation at baseline, during treatment, and after disease progression. RESULTS: Among the 10 patients treated with lorlatinib, objective response rate (ORR) was 50%. The median progression-free survival (PFS) was 13.3 months, and median overall survival (OS) was 15.6 months. At baseline, the mutation frequency of ALK in circulating tumor DNA (ctDNA) was higher in the group who received two lines of previous anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs), and a similar trend was observed for TP53. After one follow-up cycle, the decreased variant allele frequency (VAF) had a trend to be predictive for responses. In six patients in which blood samples had been taken after lorlatinib resistance, ALK compound mutations were found in three patients (50%), which were G1202R/L1196M, L1196M/D1203N, and G1202R/F1174C. The DNMT3A N403Tfs*4, ERCC3 E259D, and GNAS p.A436_P459del variants were only detected after progression in two of the other three patients without ALK compound mutations. CONCLUSIONS: The dynamic changes of genomic characteristics during lorlatinib treatment revealed the mutation landscape of Chinese patients with NSCLC after ALK-TKI resistance, indicated that the resistance profile of lorlatinib were heterogeneous, which laid the foundation for subsequent treatment to overcome lorlatinib resistance.

Third-line or above anlotinib in relapsed and refractory small cell lung cancer patients with brain metastases: A post hoc analysis of ALTER1202, a randomized, double-blind phase 2 study.

Background: The prognosis of patients with small cell lung cancer (SCLC) and brain metastases (BM) was poor. This study aimed to explore the efficacy and safety of anlotinib as third-line or above treatment in SCLC with BM. Methods: This was a subgroup analysis of the ALTER1202 trial, which was a randomized, placebo-controlled trial aimed to evaluate the role of anlotinib as third-line treatment or above in patients with SCLC. This study included patients with BM at baseline. The efficacy and safety outcomes included progression-free survival (PFS), overall survival (OS), central nervous system (CNS), objective response rate (ORR), CNS disease control rate (DCR), time to CNS progression, and adverse events (AEs). Results: Twenty-one and nine patients with BM were included in the anlotinib and placebo groups, respectively. The median PFS and OS were 3.8 months (95% confidence interval [CI]: 1.8-6.1) and 6.1 months (95% CI: 4.1-8.0) in the anlotinib group. Anlotinib was associated with a significant improvement in PFS (hazard ratio [HR] = 0.15, 95% CI: 0.04-0.51, p = 0.0005) and OS (HR = 0.26, 95% CI: 0.09-0.73, p = 0.0061) than placebo. Anlotinib significantly prolonged the time to CNS progression (p < 0.0001). The anlotinib group had a higher CNS DCR than placebo (95.2% vs. 22.2%, p = 0.0001). The most common grade 3 or higher AEs were increased lipase (19.0%), hypertension (14.3%), and hyponatremia (14.3%) in the anlotinib group. Conclusions: Anlotinib proved to have potential CNS activity and a manageable toxicity profile in patients with SCLC and BM, significantly delaying CNS progression.

An unusual ectopic thymoma clonal evolution analysis: A case report.

Thymomas and thymic carcinomas are rare and primary tumors of the mediastinum which is derived from the thymic epithelium. Thymomas are the most common primary anterior mediastinal tumor, while ectopic thymomas are rarer. Mutational profiles of ectopic thymomas may help expand our understanding of the occurrence and treatment options of these tumors. In this report, we sought to elucidate the mutational profiles of two ectopic thymoma nodules to gain deeper understanding of the molecular genetic information of this rare tumor and to provide guidance treatment options. We presented a case of 62-year-old male patient with a postoperative pathological diagnosis of type A mediastinal thymoma and ectopic pulmonary thymoma. After mediastinal lesion resection and thoracoscopic lung wedge resection, the mediastinal thymoma was completely removed, and the patient recovered from the surgery and no recurrence was found by examination until now. Whole exome sequencing was performed on both mediastinal thymoma and ectopic pulmonary thymoma tissue samples of the patient and clonal evolution analysis were further conducted to analyze the genetic characteristics. We identified eight gene mutations that were co-mutated in both lesions. Consistent with a previous exome sequencing analysis of thymic epithelial tumor, HRAS was also observed in both mediastinal lesion and lung lesion tissues. We also evaluated the intratumor heterogeneity of non-silent mutations. The results showed that the mediastinal lesion tissue has higher degree of heterogeneity and the lung lesion tissue has relatively low amount of variant heterogeneity in the detected variants. Through pathology and genomics sequencing detection, we initially revealed the genetic differences between mediastinal thymoma and ectopic thymoma, and clonal evolution analysis showed that these two lesions originated from multi-ancestral regions.

Chinese expert consensus recommendations for the administration of immune checkpoint inhibitors to special cancer patient populations.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1, programmed cell death ligand 1, and cytotoxic T lymphocyte-associated antigen-4 have shown significantly durable clinical benefits and tolerable toxicities and have improved the survival of patients with various types of cancer. Since 2018, the National Medical Products Administration of China has approved 17 ICIs as the standard treatment for certain advanced or metastatic solid tumors. As ICIs represent a broad-spectrum antitumor strategy, the populations eligible for cancer immunotherapy are rapidly expanding. However, the clinical applications of ICIs in cancer patient populations with special issues, a term that refers to complex subgroups of patients with comorbidities, special clinical conditions, or concomitant medications who are routinely excluded from prospective clinical trials of ICIs or are underrepresented in these trials, represent a great real-world challenge. Although the Chinese Society of Clinical Oncology (CSCO) has provided recommendations for screening before the use of ICIs in special populations, the recommendations for full-course management remain insufficient. The CSCO Expert Committee on Immunotherapy organized leading medical oncology and multidisciplinary experts to develop a consensus that will serve as an important reference for clinicians to guide the proper application of ICIs in special patient populations. This article is a translation of a study first published in Chinese in The Chinese Clinical Oncology (ISSN 1009-0460, CN 32-1577/R) in May 2022 (27(5):442-454). The publisher of the original paper has provided written confirmation of permission to publish this translation in Therapeutic Advances in Medical Oncology.

Quality of Life and Mental Health Status Among Cancer Patients With Metastatic Spinal Disease.

This study aimed to investigate the quality of life and mental health status and further to identify relevant risk factors among advanced cancer patients with spine metastases. This study prospectively included and analyzed 103 advanced cancer patients with spine metastases. Patient's basic information, lifestyles, comorbidities, tumor characteristics, therapeutic strategies, economic conditions, quality of life, anxiety, and depression were collected. Patient's quality of life was assessed using the Functional Assessment of Cancer Therapy-General Scale (FACT-G), and anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS). Subgroup analysis was performed based on different age groups, and a multivariate analysis was performed to test the ability of 20 potential risk factors to predict quality of life, anxiety, and depression. The mean total FACT-G score was only 61.38 ± 21.26. Of all included patients, 52.43% had skeptical or identified anxiety and 53.40% suffered from skeptical or identified depression. Patients had an age of 60 or more and <70 years had the lowest FACT-G score (54.91 ± 19.22), highest HADS anxiety score (10.25 ± 4.22), and highest HADS depression score (10.13 ± 4.94). After adjusting all other potential risk factors, age was still significantly associated with quality of life (OR = 0.57, 95%CI: 0.38-0.86, p < 0.01) and depression (OR = 1.55, 95%CI: 1.00-2.42, p = 0.05) and almost significantly associated with anxiety (OR = 1.52, 95%CI: 0.94-2.43, p = 0.08). Besides, preference to eating vegetables, time since knowing cancer diagnosis, surgical treatment at primary cancer, hormone endocrine therapy, and economic burden due to cancer treatments were found to be significantly associated with the quality of life. A number of comorbidities and economic burden due to cancer treatments were significantly associated with anxiety. Advanced cancer patients with spine metastases suffer from poor quality of life and severe anxiety and depression, especially among patients with an age of 60 or more and <70 years. Early mental health care and effective measures should be conducted to advanced cancer patients with spine metastases, and more attention should be paid to take care of patients with an age of 60 or more and <70 years in terms of their quality of life and mental health status.

The effect and mechanisms of melatonin on the proliferation and apoptosis of lung cancer cells.

The aim of the present study was to observe the effects and mechianisms of melatonin on the proliferation and apoptosis of lung cancer (LC) cells. A549 cells were treated with a concentration gradient (0-100 µM) of melatonin for 24 hours, and cell viability was detected by XTT ((2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl) -2H-tetrazolium-5-carboxanilide)) colorimetry. Melatonin with a concentration of 50 µM was selected to interact with the LC cells for ten days, and then a colony formation assay was used to detect the proliferation of the LC cells. TUNEL (Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling) staining was used to evaluate the amount of apoptosis in the two groups. Finally, Western blotting was used to detect the expression levels of related proteins in the p38MAP (mitogen-activated protein) signaling pathway. Meanwhile, another experiment, CCK-8 cell proliferation test, was conducted to detect the OD540 absorbance of LC cells at 24, 48, 72, and 96 hours. Melatonin inhibited the proliferation of LC cells in a concentration-dependent (5-100 µM) manner (P < 0.05), and inhibited the proliferation of LC cells in a time-dependent (0-96 hour) manner (P < 0.05). Melatonin (50 µM) could significantly inhibit the colony formation ability of LC cells (P < 0.05). The ratio of LC cells in the G0/G1 phase in the melatonin group increased, while the ratio of cells in the G2/M and S phase was significantly reduced (P < 0.05). Melatonin significantly promoted the apoptosis of LC cells (P < 0.05) and activate the phosphorylation of p38 (P < 0.05).

Optically Manipulated Neutrophils as Native Microcrafts In Vivo.

As the first line of host defense against invading pathogens, neutrophils have an inherent phagocytosis capability for the elimination of foreign agents and target loading upon activation, as well as the ability to transmigrate across blood vessels to the infected tissue, making them natural candidates to execute various medical tasks in vivo. However, most of the existing neutrophil-based strategies rely on their spontaneous chemotactic motion, lacking in effective activation, rapid migration, and high navigation precision. Here, we report an optically manipulated neutrophil microcraft in vivo through the organic integration of endogenous neutrophils and scanning optical tweezers, functioning as a native biological material and wireless remote controller, respectively. The neutrophil microcrafts can be remotely activated by light and then navigated to the target position along a designated route, followed by the fulfillment of its task in vivo, such as active intercellular connection, targeted delivery of nanomedicine, and precise elimination of cell debris, free from the extra construction or modification of the native neutrophils. On the basis of the innate immunologic function of neutrophils and intelligent optical manipulation, the proposed neutrophil microcraft might provide new insight for the construction of native medical microdevices for drug delivery and precise treatment of inflammatory diseases.