Repeated high­intensity focused ultrasound combined with iodine­125 seed interstitial brachytherapy offers improved quality of life and pain control for patients with advanced pancreatic cancer: A 52­patient retrospective study.

Patients diagnosed with pancreatic cancer who have 5-year survival rates of ~5% are typically in the advanced stage. Pancreatic cancer has become the third leading cause of cancer-related death in the United States and there is still a lack of effective treatments to improve patient survival rate. Hence, the purpose of the present retrospective study was to assess the potential clinical impact of repeated high-intensity focused ultrasound (HIFU) combined with iodine-125 (125I) interstitial brachytherapy for the treatment of patients with advanced pancreatic cancer who were ineligible for or declined surgery and chemotherapy. A total of 52 patients diagnosed with advanced pancreatic cancer were included in the study. At least one course of HIFU therapy combined with percutaneous ultrasound-guided 125I seed implantation was administered to each patient. The clinical assessment included an evaluation of Karnofsky Performance Scale (KPS) score at baseline, and at 1 and 2 months after combined therapy. Pain intensity was additionally evaluated with the numerical rating score (NRS). Overall survival (OS) times and survival rates at 3, 6, 9 and 12 months after combined treatment were evaluated. Adverse events commonly associated with HIFU and 125I seed implantation were recorded, and the severity of adverse events was graded according to the Common Terminology Criteria for Adverse Events, version 4. All 52 patients received successful repeated HIFU treatment combined with 125I seed implantation and were included in the analysis of efficacy and safety. The median OS time of patients was estimated to be 13.1 months (95% CI, 11.3-14.8). The survival rates at 3, 6, 9 and 12 months were 100.0, 86.5, 61.5 and 53.8%, respectively. The mean KPS score was 62.7±6.3 at baseline, 73.7±7.9 at 1 month and 68.8±6.5 at 2 months after combined treatment. KPS score increased significantly after combined therapy. The mean NRS score was 6.7±1.6 at baseline, and 4.7±1.7 and 5.4±1.5 at 1 and 2 months after combined treatment, respectively. The number of patients with severe pain and the NRS score were both significantly lower at 1 and 2 months after 125I seed implantation compared with those at baseline. No serious complications were detected during the follow-up period. In conclusion, the present study demonstrated the survival benefit and improvement in quality of life of patients with advanced pancreatic cancer receiving repeated HIFU treatment combined with 125I interstitial brachytherapy, which may provide new ideas and methods for the treatment of pancreatic cancer.

Reactive separation of ß-bromoethylbenzene from α-ß-bromoethylbenzene mixtures: a Zn2+-mediated radical polymerization mechanism.

A Zn2+-induced reactive separation method for the purification of ß-bromoethylbenzene from α-ß-bromoethylbenzene mixtures is discovered, where the selective decomposition of α-bromoethylbenzene follows a radical mechanism. Zn2+ facilitates the homolysis of the C-Br bond of halohydrocarbons with benzyl bromide, enabling the separation of the corresponding isomers with almost identical physical properties.

Ionic Conductive Organohydrogel With Ultrastretchability, Self-Healable and Freezing-Tolerant Properties for Wearable Strain Sensor.

Currently, stretchable hydrogel has attracted great attention in the field of wearable flexible sensors. However, fabricating flexible hydrogel sensor simultaneously with superstretchability, high mechanical strength, remarkable self-healing ability, excellent anti-freezing and sensing features via a facile method remains a huge challenge. Herein, a fully physically linked poly(hydroxyethyl acrylamide)-gelatin-glycerol-lithium chloride (PHEAA-GE-Gl-LiCl) double network organohydrogel is prepared via a simple one-pot heating-cooling-photopolymerization method. The prepared PHEAA-GE-Gl-LiCl organohydrogel exhibits favorable stretchability (970%) and remarkable self-healing property. Meanwhile, due to the presence of glycerol and LiCl, the PHEAA-GE-Gl-LiCl organohydrogel possesses outstanding anti-freezing capability, it can maintain excellent stretchability (608%) and conductivity (0.102 S/m) even at -40°C. In addition, the PHEAA-GE-Gl-LiCl organohydrogel-based strain sensor is capable of repeatedly and stably detecting and monitoring both large-scale human motions and subtle physiological signals in a wide temperature range (from -40°C to 25°C). More importantly, the PHEAA-GE-Gl-LiCl organohydrogel-based sensor displays excellent strain sensitivity (GF = 13.16 at 500% strain), fast response time (300 ms), and outstanding repeatability. Based on these super characteristics, it is envisioned that PHEAA-GE-Gl-LiCl organohydrogel holds promising potentials as wearable strain sensor.

Integrating waste fish scale-derived gelatin and chitosan into edible nanocomposite film for perishable fruits.

Petroleum-based plastics (such as polyethylene, polypropylene, polyvinyl chloride, polystyrene, etc.) as white waste have caused great concern in the environment. It is urgent to develop a kind of biodegradable, biocompatible and non-toxic materials to replace them. Herein, an environmental-friendly edible film for postharvest fruits refreshing application was prepared by combining the waste fish scale-derived gelatin, chitosan as well as CaCO3 nanoparticles. The as-prepared nanocomposite film showed the multifunctional features, such as UV absorption, antimicrobial, oxygen screening, excellent mechanical properties and non-toxic. In addition, the protein-polysaccharide based nanocomposite film was hydrophilic and can be easily washed away on fruits before eating. In order to inspect its preservative effect on fruits, longan and banana were chosen as the testing object. Our results showed that the edible multifunctional nanocomposite film can effectively extend the shelf life of longan by more than 3 days and banana by more than 5 days, compared with the control groups. Integrating natural biological macromolecules gelatin and chitosan into a multifunctional nanocomposite film with series of advantages of biodegradability, sustainability as well as multifunction is expected to be a potential preservative material for food packaging applications.

High-Intensity Focused Ultrasound Ablation for Unresectable Primary and Metastatic Liver Cancer: Real-World Research in a Chinese Tertiary Center With 275 Cases.

This retrospective analysis was conducted to evaluate the feasibility and safety of high-intensity focused ultrasound ablation for primary liver cancer and metastatic liver cancer. Patients with liver cancer who received high-intensity focused ultrasound were included in this analysis, including a primary liver cancer cohort (n=80) and a metastatic liver cancer cohort (n=195). The primary endpoint of our research was tumor response. The secondary endpoints included survival outcomes, visual analog scale pain scores, alpha-fetoprotein relief, and complications. Objective response rate and disease control rate were observed to be 71.8% and 81.2%, respectively, in patients with primary liver cancer and were 63.7% and 83.2% in cases with metastatic liver cancer. Alpha-fetoprotein levels and visual analogue scale levels significantly decreased after treatment compared with the baseline levels in patients with primary liver cancer (p<0.05). Median overall survival was estimated to be 13.0 and 12.0 months in the primary liver cancer and metastatic liver cancer cohorts. The 1-year survival rate was 70.69% and 48.00%, respectively. Multivariate regression analysis showed that visual analogue scale ≥ 5, longest diameter ≥ 5 cm, and portal vein invasion were the independent risk factors for poor survival in primary liver cancer. For patients with metastatic liver cancer, independent risk factors were identified as visual analogue scale ≥ 5, longest diameter ≥ 5 cm, existence of extrahepatic metastases, existence of portal vein invasion, and time to high-intensity focused ultrasound treatment from diagnosis < 3 months. Severe adverse events were rarely reported. In conclusion, high-intensity focused ultrasound might be an effective and safe option for patients with liver cancer regardless of primary and metastatic lesions.

ß­elemene inhibits the generation of peritoneum effusion in pancreatic cancer via suppression of the HIF1A­VEGFA pathway based on network pharmacology.

Pancreatic cancer remains one of the most lethal types of cancer. Late­stage pancreatic cancer patients usually suffer peritoneum effusion, which severely compromises quality of life. Great efforts have been made concerning the treatment of peritoneum effusion, including treatment with ß­elemene. Although peritoneal perfusion of ß­elemene attenuates the progression of malignant effusion without severe adverse effects in the clinic, the underlying molecular mechanism underlying the activity of ß­elemene against peritoneum effusion remains unclear. In the present study, a network pharmacology approach was undertaken to explore the mechanism of ß­elemene against peritoneum effusion. Particularly, the networks of ß­elemene and pancreatic cancer target genes were constructed based on the BATMAN­TCM and DigSee databases, respectively. Thirty­three genes, including hypoxia inducible factor 1 subunit α (HIF1A), were discovered in both networks. A potential interaction of ß­elemene with HIF1A was revealed by molecular docking simulation and co­expression analysis of pancreatic cancer datasets from The Cancer Genome Atlas (TCGA) database. Additionally, experimental validation by MTT assay demonstrated that ß­elemene suppressed proliferation of PANC­1 and BxPC3 cells and cells from peritoneum effusion in patients with pancreatic cancer. Furthermore, the protein expression levels of HIF1A and vascular endothelial growth factor A (VEGFA), as detected by western blotting, were reduced by ß­elemene. Overall, this study proposes a potential molecular mechanism illustrating that ß­elemene can block the HIF1A/VEGFA pathway, thereby inhibiting the generation of peritoneum effusion in pancreatic cancer based on network pharmacology analysis, and further highlights the importance of targeting the HIF1A/VEGF pathway as a therapeutic approach to treat peritoneum effusion in patients with pancreatic cancer.

Response of patients with locally advanced pancreatic adenocarcinoma to high-intensity focused ultrasound treatment: a single-center, prospective, case series in China.

PURPOSE: Patients with unresectable locally advanced pancreatic cancer (LAPC) are still in dire need of effective therapies. We performed this cohort study in order to assess the efficacy and safety of high-intensity focused ultrasound (HIFU) ablation in treating patients with unresectable LAPC. PATIENTS AND METHODS: Eighty-seven cases with unresectable LAPC from January 2014 to December 2016 were finally recruited according to the inclusion criteria. The primary end point of our study was OS of all the cases, and the secondary end points included 6-month and 12-month survival rate, tumor response rate, carbohydrate antigen (CA) 19-9 response rate, VAS, quality of life, and safety. RESULTS: All the 87 patients received HIFU ablation successfully, and were included in the efficacy and safety analysis. With a median follow-up of 16 months, median OS was estimated to be 12.2 months, with 95 % CI of 11.1-12.7 months. The 6-month and 12-month survival rates were 94.25% (95% CI =86.74-97.57) and 50.85% (95% CI =38.17-62.21), respectively. Multivariate analysis revealed that patients with VAS <4, Karnofsky performance status ≥80, and tumor size <3 cm have a significant improvement in their OS (adjusted HR [aHR] =0.26 [95% CI =0.12-0.57], P=0.001; aHR =0.34 [95% CI =0.17-0.68], P=0.02; and aHR =0.39 [95% CI =0.20-0.78], P=0.007; respectively). Tumor responses were observed in 32 (36.8%) of 87 patients and CA 19-9 response rate was 56.2%. Global health status, physical function, emotional function, and cognitive function of patients were significantly improved after HIFU treatment, and symptoms of fatigue and pain were significantly reduced. A total of 28.7% (25/87) of patients reported adverse events (AEs), mainly including fatigue (14/87), abdominal pain (7/87), fever (7/87), nausea (5/87), and rash (4/87). No severe AEs and HIFU-related deaths were reported. CONCLUSION: HIFU ablation might be a potentially effective and safe therapeutic option for the patients with unresectable LAPC.

Alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone inhibits cell proliferation, invasion, and migration in gastric cancer in part via autophagy.

Gastric cancer is a leading cause of mortality worldwide. Alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone is a type of limonoid mainly isolated from Cedrela odorata (Meliaceae) that has been shown to suppress cell proliferation in several human carcinoma cell lines. In this study, we investigated the anti-cancer ability of alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone and its underlying mechanism in MKN45 cells. Alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone induced excess reactive oxygen species (ROS) accumulation. Transwell and wound healing assays demonstrated that alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone inhibited the invasion and migration ability of MKN45 cells. Moreover, autophagy-related proteins Beclin-1, Atg5, and Atg7 were up-regulated. Light chain 3 (LC3)-I protein was converted into LC3-II under alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone exposure. Transmission electron microscopy demonstrated that alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone treatment resulted in the formation of autophagosomes. Immunofluorescence assays suggested that alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone treatment elicited dot formation of green fluorescent protein (GFP)-LC3. 3-methyladenine (3-MA), an autophagy inhibitor, demonstrated that autophagy promoted death in MKN45 cells. Western blotting showed that ROS/mitogen activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways play crucial roles in the intrinsic mechanism of alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone's activity. The combined use of N-acetyl-L-cysteine (NAC) or U0126 validated the regulatory role of ROS/MEK/ERK signaling pathways. Alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone administration inhibited the growth of MKN45 xenograft tumors in nude mice and suppressed Ki67 expression. More importantly, a similar effect was achieved in a patient-derived xenograft (PDX) model, which is more relevant to clinical application. Taken together, alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone has the potential to be further developed into an anti-tumor agent for clinical treatment of gastric cancer.

High-intensity focused ultrasound (HIFU) treatment for uterine fibroids: a meta-analysis.

PURPOSE: High-intensity focused ultrasound (HIFU) is a non-invasive uterine-preserving treatment alternative to hysterectomy for women with fibroids. METHODS: We performed this meta-analysis to evaluate the efficacy of HIFU in the treatment of women with symptomatic fibroids comparing it to other approaches including medical treatment with mifepristone (Mife), traditional surgery with myomectomy or hysterectomy (MYC/HRM), and radiofrequency ablation (RF). 16 studies with 1725 women were included. RESULTS: The pooled data of HIFU comparing it to other methods in terms of complete or partial response rate (CR/PR) was not significantly better, but in subgroup analysis, the response rate was significantly higher than Mife, significantly lower than RF and comparable to MYC/HRM, respectively. For the endpoints of safety, the superiority of HIFU compared to MYC/HMR or Mife was found to be significant in terms of pain/discomfort, fever, transfusion, genital tract, gastrointestinal tract, and anesthesia-related complications, while no superiority was identified for skin burn, urinary tract, and nervous system complications. CONCLUSION: These results suggest that HIFU treatment of uterine leiomyomas leads to clinical improvement with few significant clinical complications and adverse events.

Influence of the electronic structures on the heterogeneous photoelectrocatalytic performance of Ti/RuxSn1-xO2 electrodes.

DSA-type Ti/RuxSn1-xO2 electrodes were prepared by thermal decomposition method as photoelectrocatalysts (PECs) and extensively characterized by various sophisticated techniques. First-principles calculations was employed to study the effects of Ru content on the electronic structures of the RuxSn1-xO2 coatings. The photoelectric-synergistic catalytic activity of the Ti/RuxSn1-xO2 electrodes was evaluated for the degradation of methyl orange (MO) in aqueous solution. The results show that the RuO2-SnO2 solid solution could be formed. The band gaps of the RuxSn1-xO2 coatings gradually decreased and eventually turned into metallic conductivity with the increase of ruthenium content. As a PEC electrode, reducing band gap is helpful to improve electronic conductivity and the electrocatalytic activity, but not always advantageous to increase the photocatalytic activity. Because too narrow band gap will sacrifice the photogenerated charge carriers and thus reduce photocatalytic activity of the electrode. In our experiments, the rate constant of Ti/Ru0.05Sn0.95O2 electrode increased with increasing Ru content and exhibited the maximum rate for 5% Ru loading. The stability test showed the photoelectrocatalytic activity of the Ti/Ru0.05Sn0.95O2 electrode almost had no attenuation after 100h photoelectrolysis, revealing that this electrode has good long-term stability.

Concurrent gemcitabine and high-intensity focused ultrasound therapy in patients with locally advanced pancreatic cancer.

This phase II trial was conducted to evaluate the safety and efficacy of concurrent gemcitabine and high-intensity focused ultrasound (HIFU) therapy in patients with locally advanced pancreatic cancer. Patients with localized unresectable pancreatic adenocarcinoma in the head or body of the pancreas received gemcitabine (1000 mg/m) intravenously over 30 min on days 1, 8, and 15, and concurrent HIFU therapy on days 1, 3, and 5. The treatment was given every 28 days. Thirty-seven (94.9%) of the 39 patients were assessable for response, and two cases of complete response and 15 cases of partial response were confirmed, giving an overall response rate of 43.6% [95% confidence interval (CI), 28.0-59.2%]. The median follow-up period was 16.5 months (range: 8.0-28.5 months). The median time to progression and overall survival for all patients were 8.4 months (95% CI, 5.4-11.2 months) and 12.6 months (95% CI, 10.2-15.0 months), respectively. The estimates of overall survival at 12 and 24 months were 50.6% (95% CI, 36.7-64.5%) and 17.1% (95%CI, 5.9-28.3%), respectively. A total of 16.2% of patients experienced grade 3/4 neutropenia. Grade 3 thrombocytopaenia was documented in two (5.4%) patients. Grade 3 nausea/vomiting and diarrhea were observed in three (8.1%), and two (5.4%) patients, respectively. Grade 1 or 2 fever was detected in 70.3% of patients. Twenty-eight patients (71.8%) complained of abdominal pain consistent with tumor-related pain before HIFU therapy. Pain was relieved in 22 patients (78.6%). In conclusion, concurrent gemcitabine and HIFU is a tolerated treatment modality with promising activity in patients with previously untreated locally advanced pancreatic cancer.