Effects of Telemedicine on Informal Caregivers of Patients in Palliative Care: Systematic Review and Meta-Analysis.

Background: Telemedicine technology is a rapidly developing field that shows immense potential for improving medical services. In palliative care, informal caregivers assume the primary responsibility in patient care and often face challenges such as increased physical and mental stress and declining health. In such cases, telemedicine interventions can provide support and improve their health outcomes. However, research findings regarding the use of telemedicine among informal caregivers are controversial, and the efficacy of telemedicine remains unclear. Objective: This study aimed to evaluate the impacts of telemedicine on the burden, anxiety, depression, and quality of life of informal caregivers of patients in palliative care. Methods: A systematic literature search was conducted using the PubMed, Embase, Web of Science, CENTRAL, PsycINFO, CINAHL Plus with Full Text, CBM, CNKI, WanFang, and VIP databases to identify relevant randomized controlled trials published from inception to March 2023. Two authors independently screened the studies and extracted the relevant information. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool. Intervention effects were estimated and sensitivity analysis was conducted using Review Manager 5.4, whereas 95% prediction intervals (PIs) were calculated using R (version 4.3.2) and RStudio. Results: A total of 9 randomized controlled trials were included in this study. The meta-analysis indicated that telemedicine has reduced the caregiving burden (standardized mean differences [SMD] -0.49, 95% CI -0.72 to -0.27; P<.001; 95% PI -0.86 to -0.13) and anxiety (SMD -0.23, 95% CI -0.40 to -0.06; P=.009; 95% PI -0.98 to 0.39) of informal caregivers; however, it did not affect depression (SMD -0.21, 95% CI -0.47 to 0.05; P=.11; 95% PI -0.94 to 0.51) or quality of life (SMD 0.35, 95% CI -0.20 to 0.89; P=.21; 95% PI -2.15 to 2.85). Conclusions: Although telemedicine can alleviate the caregiving burden and anxiety of informal caregivers, it does not significantly reduce depression or improve their quality of life. Further high-quality, large-sample studies are needed to validate the effects of telemedicine. Furthermore, personalized intervention programs based on theoretical foundations are required to support caregivers.

Cuproptotic nanoinducer-driven proteotoxic stress potentiates cancer immunotherapy by activating the mtDNA-cGAS-STING signaling.

Proteotoxic stress, caused by the accumulation of abnormal unfolded or misfolded cellular proteins, can efficiently activate inflammatory innate immune response. Initiating the mitochondrial proteotoxic stress might go forward to enable the cytosolic release of intramitochondrial DNA (mtDNA) for the immune-related mtDNA-cGAS-STING activation, which however is easily eliminated by a cell self-protection, i.e., mitophagy. In light of this, a nanoinducer (PCM) is reported to trigger mitophagy-inhibited cuproptotic proteotoxicity. Through a simple metal-phenolic coordination, PCMs reduce the original Cu2+ with the phenolic group of PEG-polyphenol-chlorin e6 (Ce6) into Cu+. Cu+ thereby performs its high binding affinity to dihydrolipoamide S-acetyltransferase (DLAT) and aggregates DLAT for cuproptotic proteotoxic stress and mitochondrial respiratory inhibition. Meanwhile, intracellular oxygen saved from the respiratory failure can be utilized by PCM-conjugated Ce6 to boost the proteotoxic stress. Next, PCM-loaded mitophagy inhibitor (Mdivi-1) protects proteotoxic products from being mitophagy-eliminated, which allows more mtDNA to be released in the cytosol and successfully stimulate the cGAS-STING signaling. In vitro and in vivo studies reveal that PCMs can upregulate the tumor-infiltrated NK cells by 24% and enhance the cytotoxic killing of effector T cells. This study proposes an anti-tumor immunotherapy through mitochondrial proteotoxicity.

Dual-Epigenetically Relieving the MYC-Correlated Immunosuppression via an Advanced Nano-Radiosensitizer Potentiates Cancer Immuno-Radiotherapy.

Cancer cells can upregulate the MYC expression to repair the radiotherapy-triggered DNA damage, aggravating therapeutic resistance and tumor immunosuppression. Epigenetic treatment targeting the MYC-transcriptional abnormality may intensively solve this clinical problem. Herein, 5-Aza (a DNA methyltransferase inhibitor) and ITF-2357 (a histone deacetylase inhibitor) are engineered into a tungsten-based nano-radiosensitizer (PWAI), to suppress MYC rising and awaken robust radiotherapeutic antitumor immunity. Individual 5-Aza depletes MYC expression but cannot efficiently awaken radiotherapeutic immunity. This drawback can be overcome by the addition of ITF-2357, which triggers cancer cellular type I interferon (IFN-I) signaling. Coupling 5-Aza with ITF-2357 ensures that PWAI does not evoke the treated model with high MYC-related immune resistance while amplifying the radiotherapeutic tumor killing, and more importantly promotes the generation of IFN-I signal-related proteins involving IFN-α and IFN-ß. Unlike the radiation treatment alone, PWAI-triggered immuno-radiotherapy remarkably enhances antitumor immune responses involving the tumor antigen presentation by dendritic cells, and improves intratumoral recruitment of cytotoxic T lymphocytes and their memory-phenotype formation in 4T1 tumor-bearing mice. Downgrading the radiotherapy-induced MYC overexpression via the dual-epigenetic reprogramming strategy may elicit a robust immuno-radiotherapy.

PhotoPyro-Induced cGAS-STING Pathway Activation Enhanced Anti-Melanoma Immunotherapy via a Manganese-Coordinated Nanomedicine.

Malignant melanoma is an aggressive skin cancer with a high metastatic and mortality rate. Owing to genetic alterations, melanoma cells are resistant to apoptosis induction, which reduces the efficacy of most adjuvant systemic anticancer treatments in clinical. Here, a noninvasive strategy for anti-melanoma immunotherapy based on a manganese-coordinated nanomedicine is provided. Supplemented with photoirradiation, photon-mediated reactive oxygen species generation by photosensitizer chlorin e6 initiates photon-controlled pyroptosis activation (PhotoPyro) and promotes antitumor immunity. Simultaneously, photoirradiation-triggered double-stranded DNA generation in the cytosol would activate the Mn2+ -sensitized cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which further augment the PhotoPyro-induced immune response. The syngeneic effect of these immunostimulatory pathways significantly benefits dendritic cell maturation by damage-associated molecular patterns and proinflammatory cytokines secretion, thereby activating T cells and remarkably eliciting a systemic antitumor immune response to inhibiting both primary and distant tumor growth. Collaboratively, the photoirradiation-triggered PhotoPyro and cGAS-STING pathway activation by nanomedicine administration could enhance the antitumor capacity of immunotherapy and serve as a promising strategy for melanoma treatment.

Klippel-Trenaunay syndrome and pregnancy: A Case-Report.

Klippel-Trenaunay Syndrome is a benign disease with a low incidence rate. Pregnant women with KTS may be at increased risk of thrombosis and coagulopathy due to normal hemodynamic changes during pregnancy. The choice of delivery route for KTS pregnant woman needs rigorous evaluation. This study reported a case of successful delivery by oxytocin combined with balloon catheter induction for the first time, providing more options for KTS pregnant woman. At the same time, this study reported a successful case of labor induced by oxytocin combined with balloon catheter for the first time, which further explored the obstetric management of pregnant women with KTS and provided them with more delivery options.

Supermolecular nanovehicles co-delivering TLR7/8-agonist and anti-CD47 siRNA for enhanced tumor immunotherapy.

Cancer immunotherapy is the most promising method for tumor therapy in recent years, among which the macrophages play a critical role in the antitumor immune response. However, tumor-associated macrophages (TAMs) usually display the tumor-promoting M2 phenotype rather than the tumor-killing M1 phenotype. Moreover, the over-expressed CD47 on tumor cells severely hinders the function of macrophages by blocking the CD47/SIRPα pathway. Herein, a nano-assembly system of CHTR/siRNA was constructed through the host-guest interaction of a hyperbranched amino-functionalized ß-cyclodextrin and immune agonist imiquimod (R848), while CD47 siRNA was loaded inside through electrostatic interaction. The Toll-like receptor (TLR) 7/8 agonist R848 can "re-educate" macrophages from the protumoral M2 phenotype to antitumoral M1 phenotype, while CD47 siRNA can down-regulate the "don't eat me" CD47 signal on the surface of cancer cells and enhance the phagocytosis of cancer cells by macrophages. Through the dual regulation of TAMs, the immunosuppressive tumor microenvironment was relieved, and the host-guest drug-carrying system resulted in synergistic immunotherapy effect on tumors and inhibited tumor growth. The facile self-assembly of nanodrug offers a new strategy in co-delivery of multiple therapeutic agents for cascade cancer immunotherapy.

Metal-Phenolic Nanomedicines Regulate T-Cell Antitumor Function for Sono-Metabolic Cancer Therapy.

Cancer cells outcompete tumor-infiltrating T lymphocytes (TILs) for glucose uptake, manipulating a glucose-deprived tumor microenvironment (TME) with high accumulation of lactate, which impairs CD8+ TIL effector function, however supports the immune suppression of regulatory T (Treg) cells. Aerobic glycolysis inhibition coupled with mitochondrial dysfunction in cancer cells may reprogram TME to destabilize Treg cells and, more importantly, facilitate CD8+ T cell activation and cytotoxic killing. Here, a sono-metabolic cancer therapy via hyaluronic acid (HA)-modified metal-phenolic nanomedicine (HPP-Ca@GSK) is proposed to accomplish the aforementioned goals. Abrogating lactate dehydrogenase A (LDHA) by delivering GSK2837808A (GSK, LDHA inhibitor) successfully suppresses aerobic glycolysis in cancer cells and creates high-glucose, low-lactate conditions, satisfying the glucose nutrition required by CD8+ TILs but destabilizing Treg cells. Meanwhile, depending on ultrasound-mediated oxidative stress, more than 3-fold of calcium (from HPP-Ca@GSK) is mitochondrion-overloaded, amplifying mitochondrial dysfunction and promoting the cancer cellular release of damage-associated molecular patterns for more CD8+ T cell activation and tumor infiltration. In vitro and in vivo studies demonstrate that HPP-Ca@GSK-based sono-metabolic treatment exhibits impressive anticancer activity. Cooperating with anticytotoxic T lymphocyte-associated protein-4 antibodies for enhanced Treg cell destabilization further improves therapeutic efficacy. These findings provide a metabolic intervention strategy for cancer immunotherapy.

Self-Degradable Nanogels Reshape Immunosuppressive Tumor Microenvironment via Drug Repurposing Strategy to Reactivate Cytotoxic CD8+ T Cells.

Intratumoral CD8+ T cells are crucial for effective cancer immunotherapy, but an immunosuppressive tumor microenvironment (TME) contributes to dysfunction and insufficient infiltration. Drug repurposing has successfully led to new discoveries among existing clinical drugs for use as immune modulators to ameliorate immunosuppression in TME and reactivate T-cell-mediated antitumor immunity. However, due to suboptimal tumor bioavailability, the full potential of immunomodulatory effects of these old drugs has not been realized. The self-degradable PMI nanogels carrying two repurposed immune modulators, imiquimod (Imi) and metformin (Met), are reported for TME-responsive drug release. It remodels the TME through the following aspects: 1) promoting dendritic cells maturation, 2) repolarizing M2-like tumor-associated macrophages, and 3) downregulating PD-L1 expression. Ultimately, PMI nanogels reshaped the immunosuppressive TME and efficiently promote CD8+ T cell infiltration and activation. These results support that PMI nanogels can potentially be an effective combination drug for enhancing the antitumor immune response of anti-PD-1 antibodies.

SIS membrane modification to improve antimicrobial and osteogenic properties for guide bone regeneration.

The guided bone regeneration (GBR) technique is the most common and durable approach to repairing bone defects in periodontal surgery. However, membrane exposure causes bacterial infiltration, which lowers the functional integrity of the barrier membrane and destroys bone repair. Here, an antibacterial peptide-modified small intestinal submucosa (SIS) membrane is used as a new GBR membrane for effective bone regeneration. The peptide JH8194 was placed into chitosan microspheres to preserve its stability and allow for sustained release, which realizes rapid and efficient functional modification of the SIS membrane. Biocompatibility and certain antibacterial activities were found in the modified SIS membrane (SIS@CS-JH8194). Additionally, in vitro experiments showed that SIS@CS-JH8194 promoted the expression of osteogenic-related factors and decreased the secretion of inflammatory factors in rat bone mesenchymal stem cells. In vivo experiments showed that SIS@CS-JH8194 could effectively promote bone regeneration in rat skull defects. In this work, we created a new antibacterial GBR membrane to help avoid postoperative infection and improve bone tissue regeneration.

Effectiveness of a novel traction device in endoscopic submucosal dissection for colorectal lesions.

BACKGROUND: Among all types of superficial gastrointestinal (GI) neoplasms, colorectal lesions are recognized as one of the most difficult locations to operate, due to the limited operation space, physiological bends, poor visualization of the submucosal dissection plane sheltered by colorectal crinkle wall, and the thin intestinal mucosa layer which is easy to perforation. The purpose of this prospective study is to evaluate the feasibility, efficacy, and safety of a novel endoscopic traction technique in assisting the endoscopic submucosal dissection (ESD) procedure in colorectal lesions. METHOD: A total of 117 patients with colonic lesions who underwent endoscopic treatment were enrolled between August 2020 and January 2021 at the endoscopic center of Beijing Chao-yang Hospital of Capital Medical University. Based on whether traction device was used during the operation, 60 and 57 patients were assigned to the conventional ESD group and clips and rubber band triangle traction-assisted ESD group (CRT-ESD, in which three clips and a rubber band were used to form an elastic triangular traction device), respectively. The total procedure time (TPT), submucosal dissection time (SDT), submucosal dissection speed (SDS), and rate of adverse events of the two groups were analyzed. RESULTS: After excluding patients who did not undergo treatment (conventional ESD, 1; CRT-ESD, 4), 112 patients were included in the study (conventional ESD, 59; CRT-ESD, 53). The baseline characteristics of the patients were well balanced between the two groups. The TPT (58.71 ± 26.22 min vs 33.58 ± 9.88 min, p < 0.001) and SDT (49.24 ± 23.75 min vs 26.34 ± 8.75 min, p < 0.001) were significantly different between the conventional ESD group and CRT-ESD group. The CRT-ESD group had significantly higher SDS than that of the traditional ESD group (0.54 ± 0.42 cm2/min vs 0.89 ± 0.40 cm2/min, p < 0.001). There were 4 (6.8%) cases of perforation in the traditional ESD group, and no perforation occurred in traction-assisted ESD. CONCLUSIONS: Compared with traditional ESD, CRT-ESD with clip and rubber band is both safer and more effective in the treatment of colorectal lesions.

Association Between Passive Smoking and Menstrual Discomfort: A Cross-Sectional Study of 2,571 Non-smoking Chinese Nurses.

Introduction: Menstrual discomfort affects women's quality of life, which is an important public health issue. Evidence confirming the link between passive smoking and menstrual discomfort is limited. Therefore, the aim of this study is to investigate the aforementioned topic on the basis of a cross-sectional study of 2,571 non-smoking Chinese nurses. Methods: Demographic information and passive smoking were assessed using a self-administered questionnaire. Menstrual discomfort was characterized as dysmenorrhea, illness or weakness, bed rest, and restlessness during menstruation, which was assessed using a modified version of the Cornell Medical Index-Health Questionnaire. Multivariate-adjusted odds ratio (OR) and 95% confidence intervals (CIs) were estimated using the logistic regression model. Results: A total of 1:195 nurses (46.48%) were exposed to passive smoking. Compared with non-passive smoking nurses, passive smoking nurses were more likely to have menstrual discomfort symptoms (72.38 vs. 64.39%), especially symptoms of dysmenorrhea (49.54 vs. 42.08%), illnesses or weakness (48.28 vs. 42.08%), and restlessness during menstruation (53.05 vs. 46.22%). Exposure to passive smoking was significantly associated with menstrual discomfort (OR = 1.41, 95%CI: 1.19-1.67), especially symptoms of dysmenorrhea (OR = 1.32, 95%CI: 1.13-1.56), illness or weakness (OR = 1.24, 95%CI: 1.06-1.46), and restlessness (OR = 1.26, 95%CI: 1.08-1.48) during menstruation. The subgroup analyses, stratified by age, children, and marital status, agreed with the main findings. Conclusions: Exposure to passive smoking was related to symptoms of dysmenorrhea and menstrual discomfort.

Impact of body mass index, weight gain, and metabolic disorders on survival and prognosis in patients with breast cancer who underwent chemotherapy.

BACKGROUND: Weight gain during chemotherapy in patients with breast cancer contributes to their poor prognosis. However, a growing number of studies have found that metabolic disorders seem to play a more important role in breast cancer prognosis than weight gain. This study aimed to explore the prognostic effects of body mass index (BMI), weight gain, and metabolic disorders on the overall survival (OS) and prognosis of patients with breast cancer who underwent chemotherapy. METHODS: Data from the inpatient medical records of patients with breast cancer who underwent chemotherapy at the Beijing Cancer Hospital Breast Cancer Center from January to December 2010 were retrospectively collected, and the patients were followed up until August 2020. RESULTS: A total of 438 patients with stages I to III breast cancer met the inclusion and exclusion criteria. Forty-nine (11.19%) patients died, while 82 (18.72%) patients had tumor recurrence and metastasis at the last follow-up (August 2020). From the time of diagnosis until after chemotherapy, no significant differences were observed in the body weight (t = 4.694, P < 0.001), BMI categories (χ2 = 19.215, P = 0.001), and incidence of metabolic disorders (χ2 = 24.841, P < 0.001); the BMI categories and weight change had no effect on the OS. Both univariate (χ2 = 6.771, P = 0.009) and multivariate survival analyses (hazard ratio = 2.775, 95% confidence interval [CI]: 1.326-5.807, P = 0.007) showed that low high-density lipoprotein cholesterol (HDL-C) levels at diagnosis had a negative impact on the OS. The multivariate logistic regression analysis showed that the HDL-C level at diagnosis (odds ratio [OR] = 2.200, 95% CI: 0.996-4.859, P = 0.051) and metabolic disorders after chemotherapy (OR = 1.514, 95% CI: 1.047-2.189, P = 0.028) are risk factors for poor prognosis in patients with breast cancer. CONCLUSIONS: Chemotherapy led to weight gain and aggravated the metabolic disorders in patients with breast cancer. Low HDL-C levels at diagnosis and metabolic disorders after chemotherapy may have negative effects on the OS and prognosis of patients with breast cancer.

Association Between Passive Smoking and Health Among Chinese Nurses: A Cross-Sectional Study.

This study aimed to investigate the association between passive smoking and physical and psychological health in Chinese nurses. Participants of this cross-sectional study comprised 2,484 non-smoking nurses. Passive smoking and demographic information were assessed using a self-administered questionnaire. Physical, psychological, and overall health status of nurses were measured using the Cornell Medical Index (CMI) health questionnaire. Multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for nurses' health were estimated by exposure to passive smoking using unconditional logistic regression models. A total of 1,219 nurses (49.07%) were exposed to passive smoking. Of these, 609 (24.52%), 160 (6.44%), and 587 (23.63%) nurses had poorer physical, mental, and overall health, respectively. After adjusting for other confounding factors, compared with the non-passive smoking group, passive smoking was associated with poor physical (OR = 1.51, 95% CI: 1.25-1.83), mental (OR = 1.48, 95% CI: 1.07-2.07), and overall (OR = 1.58, 95% CI: 1.30-1.93) health of nurses, respectively. We also carried out subgroup analyses stratified by age, department, and professional title, which showed that most findings supported the main results. This study demonstrated that exposure to passive smoking was a risk factor for overall decreased physical and mental health status among Chinese nurses.

Comparing long-term outcomes between endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for type II esophagogastric junction neoplasm.

BACKGROUND: Endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) are used to remove esophagogastric junction (EGJ) neoplasm. This study aimed to compare feasibility, safety, and effectiveness between ESD and EMR to help endoscopists choose treatment methods. METHODS: A total of 130 patients with EGJ neoplasm underwent endoscopic resection, including 52 patients with EMR and 78 patients with ESD. Cap-assisted EMR (EMRC) was performed with typical sequences. Larger lesions required removal in multiple pieces (i.e., piecemeal EMR). The ESD procedures were included that marking the periphery of the lesion, submucosa injected, circumferentially cutting and submucosal dissection. Resection time, adverse events, en bloc resection rate, R0 resection rate and recurrence rate were compared between the two groups. RESULTS: There were no significant differences in demographic characteristics or histopathological features between the two groups. Resection time was longer in the ESD group than in the EMR group (64.4±33.9 vs. 22.1±8.0 minutes; P<0.01). Adverse events were more common in the ESD group than in the EMR group (16.7% vs. 3.8%; P=0.03), including bleeding (7.7% vs. 3.8%), perforation (5.1% vs. 0%) and stenosis (5.1% vs. 0%). The en bloc resection rate and R0 resection rate were much higher in the ESD group than in the EMR group (98.7% and 92.3% vs. 23.1% and 23.1%, respectively; P<0.01). The 5-year overall survival rate and disease-free survival rate were 100% vs. 92.0% and 100% vs. 90.1% between the ESD and EMR groups, respectively (P=0.01 and P=0.01). The 5-year cancer-specific survival rate was 100% vs. 96.0% between the ESD and EMR groups (P=0.08). The recurrence rate was lower in the ESD group than in the EMR group (0% vs. 9.6%; P=0.01). CONCLUSIONS: ESD is an acceptable first-line endoscopic treatment for type II EGJ neoplasm, however, it is time-consuming and has a higher rate of adverse events. Furthermore, EMR is a safe and alternative technique, particularly when EMR could achieve en bloc resection.

Automated software-assisted diagnosis of esophageal squamous cell neoplasia using high-resolution microendoscopy.

BACKGROUND AND AIMS: High-resolution microendoscopy (HRME) is an optical biopsy technology that provides subcellular imaging of esophageal mucosa but requires expert interpretation of these histopathology-like images. We compared endoscopists with an automated software algorithm for detection of esophageal squamous cell neoplasia (ESCN) and evaluated the endoscopists' accuracy with and without input from the software algorithm. METHODS: Thirteen endoscopists (6 experts, 7 novices) were trained and tested on 218 post-hoc HRME images from 130 consecutive patients undergoing ESCN screening/surveillance. The automated software algorithm interpreted all images as neoplastic (high-grade dysplasia, ESCN) or non-neoplastic. All endoscopists provided their interpretation (neoplastic or non-neoplastic) and confidence level (high or low) without and with knowledge of the software overlay highlighting abnormal nuclei and software interpretation. The criterion standard was histopathology consensus diagnosis by 2 pathologists. RESULTS: The endoscopists had a higher mean sensitivity (84.3%, standard deviation [SD] 8.0% vs 76.3%, P = .004), lower specificity (75.0%, SD 5.2% vs 85.3%, P < .001) but no significant difference in accuracy (81.1%, SD 5.2% vs 79.4%, P = .26) of ESCN detection compared with the automated software algorithm. With knowledge of the software algorithm, the specificity of the endoscopists increased significantly (75.0% to 80.1%, P = .002) but not the sensitivity (84.3% to 84.8%, P = .75) or accuracy (81.1% to 83.1%, P = .13). The increase in specificity was among novices (P = .008) but not experts (P = .11). CONCLUSIONS: The software algorithm had lower sensitivity but higher specificity for ESCN detection than endoscopists. Using computer-assisted diagnosis, the endoscopists maintained high sensitivity while increasing their specificity and accuracy compared with their initial diagnosis. Automated HRME interpretation would facilitate widespread usage in resource-poor areas where this portable, low-cost technology is needed.

Risk factors for complications after endoscopic treatment in Chinese patients with early esophageal cancer and precancerous lesions.

BACKGROUND: This study aimed to analyze the risk factors for complications after endoscopic treatment of early esophageal cancer and precancerous lesions and provides evidence for developing preventive measures against these complications. METHODS: The clinical data of patients with early esophageal cancer and precancerous lesions treated in the Department of Endoscopy, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from January 2009 to December 2015 were analyzed. The risk factors related to delayed bleeding, perforation, and stenosis were assessed. RESULTS: Of 459 patients, 15 (3.3%) had delayed bleeding, 16 (3.5%) had perforation, and 82 (17.9%) had stenosis. Conservative treatment was performed for patients with bleeding and perforation, and endoscopic dilation was performed to relieve stenosis. The independent risk factors for delayed bleeding were lesion size (OR = 1.51, P = 0.020), circumferential diameter [odds ratio (OR) = 1.24, P = 0.037]. The kind of operation method [endoscopic submucosal dissection (ESD)/cap-based endoscopic resection (EMR-Cap): OR = 15.38, P = 0.013) was the independent risk factor for perforation. The independent predictors of stenosis were circumferential diameter (OR = 1.58, P < 0.001), lesion in the neck (OR = 0.12, P = 0.003), and surgical time (OR = 1.02, P = 0.007). CONCLUSION: Few complications occur after the endoscopic treatment of early esophageal cancer and precancerous lesions which can be treated by endoscopic and conservative medical therapies. Strict operational training is required for ESD treatment.

Nanomedicine-based tumor photothermal therapy synergized immunotherapy.

The emerging anti-tumor immunotherapy has made significant progress in clinical application. However, single immunotherapy is not effective for all anti-tumor treatments, owing to the low objective response rate and the risk of immune-related side effects. Meanwhile, photothermal therapy (PTT) has attracted significant attention because of its non-invasiveness, spatiotemporal controllability and small side effects. Combining PTT with immunotherapy overcomes the issue that single photothermal therapy cannot eradicate tumors with metastasis and recurrence. However, it improves the therapeutic effect of immunotherapy, as the photothermal therapy usually promotes release of tumor-related antigens, triggers immune response by the immunogenic cell death (ICD), thereby, endowing unique synergistic mechanisms for cancer therapy. This review summarizes recent research advances in utilizing nanomedicines for PTT in combination with immunotherapy to improve the outcome of cancer treatment. The strategies include immunogenic cell death, immune agonists and cancer vaccines, immune checkpoint blockades and tumor specific monoclonal antibodies, and small-molecule immune inhibitors. The combination of synergized PTT-immunotherapy with other therapeutic strategies is also discussed.

Endoscopic resection techniques for squamous premalignant lesions and early carcinoma of the esophagus: ER-Cap, MBM, and ESD, how do we choose? A multicenter experience.

BACKGROUND: Endoscopic resection cap technique (ER-Cap), multiband mucosectomy (MBM), and endoscopic submucosal dissection (ESD) have been widely applied in the treatment of esophageal squamous neoplasia and cancer. However, little is known with regards to the comparison of these methods. This study aimed to compare the feasibility, safety, effectiveness, and costs of these three techniques. METHODS: A retrospective analysis of patients with squamous premalignant or early malignant lesions of the esophagus undergoing ER-Cap, MBM, or ESD from January 2009 to December 2015 in one of the centers in China was performed. The procedural data and follow-up data for all patients were recorded. RESULTS: A total of 672 patients with 733 lesions were included; 148 lesions (133 patients) were treated with ER-Cap, 427 lesions (388 patients) with MBM, and 158 lesions (151 patients) with ESD. The mean age was 61.59 years and the male-to-female ratio was 2.78:1. The operation time was significantly shorter for ER-Cap (29.26 ± 16.73 mins, p < 0.001) group, and the hospitalization costs were significantly lower in the MBM group (20,942.03 ± 8435.56ï¿¥, p = 0.003). The resection sample size of ESD was significantly larger (4.40 ± 1.20 cm, p < 0.001) and the en bloc resection rate of ESD was significantly higher (p < 0.001) than that of the other two groups. The frequencies of perforation, bleeding, and cicatricial stenosis were significantly lower in the MBM group (p < 0.001, p = 0.011, p = 0.009). Three local recurrences were observed in the ER-Cap group, while no recurrence was observed in MBM and ESD groups. There were three and two metastatic patients observed in the MBM and ESD groups, respectively. CONCLUSIONS: ER-Cap, MBM, and ESD are all minimally invasive, safe, and effective methods for treating early esophageal squamous cell carcinoma. MBM could be considered as a good alternative when performed by a less-experienced endoscopist in high-incidence areas with limited resources.

RGFP966 Suppresses Tumor Growth and Migration Through Inhibition of EGFR Expression in Hepatocellular Carcinoma Cells in vitro.

PURPOSE: Histone deacetylase 3 (HDAC3) has been suggested to play a role in hepatocellular carcinoma (HCC). In the present report, we aimed to identify the effects of RGFP966, a specific HDAC3 inhibitor, on the cell proliferation and migration of HCC cell lines. METHODS: Human HCC cell lines, which were identified using short tandem repeat (STR) DNA profiling analysis, were used in this report. Cell proliferation assay was used to identify the growth viability of cells. Wound healing and transwell assay were used to identify the migration ability of cells. Further, a human phospho-receptor tyrosine kinases array kit was used to screen out RGFP966 effects on key receptor tyrosine kinases. Then, the mRNA expression was quantified by real-time PCR, and protein expression was identified by Western blot immunoassay. RESULTS: We found that RGFP966 inhibited both proliferation and migration of HCC cells. Further, RGFP966 represses the expression and phosphorylation levels of epidermal growth factor receptor (EGFR) in HCC cells. Moreover, HDAC3 is involved in the inhibition of EGFR by RGFP966. Overall, we elucidated an inhibitive function of RGFP966 in HCC progression. CONCLUSION: RGFP966 inhibits EGFR signaling pathway and suppresses proliferation and migration of HCC cells.

Integrating Fluorinated Polymer and Manganese-Layered Double Hydroxide Nanoparticles as pH-activated 19 F MRI Agents for Specific and Sensitive Detection of Breast Cancer.

19 F magnetic resonance imaging (19 F MRI) agents capable of being activated upon interactions with cancer triggers are attracting increasing attention, although challenges still remain for precise and specific detection of cancer tissues. In this study, a novel hybrid 19 F MRI agent for pH-sensitive detection of breast cancer tissues is reported, a composite system designed by conjugating a perfluoropolyether onto the surface of manganese-incorporated layered double hydroxide (Mn-LDH@PFPE) nanoparticles. The 19 F NMR/MRI signals from aqueous solutions of Mn-LDH@PFPE nanoparticles are quenched at pH 7.4, but "turned on" following a reduction in pH to below 6.5. This is due to partial dissolution of Mn2+ from the Mn-LDH nanoparticles and subsequent reduction in the effect of paramagnetic relaxation. Significantly, in vivo experiments reveal that an intense 19 F MR signal can be detected only in the breast tumor tissue after intravenous injection of Mn-LDH@PFPE nanoparticles due to such a specific activation. Thus pH-activated Mn-LDH@PFPE nanoparticles are a potential "smart" 19 F MRI agent for precise and specific detection of cancer diseases.