Cascade Tumor Therapy Platform for Sensitized Chemotherapy and Penetration Enhanced Photothermal Therapy.

As a stand-alone therapy strategy may not be sufficient for effective cancer treatment and a combination of chemotherapy with other therapies is a main trend in cancer treatment. A combination of chemotherapy and photothermal therapy (PTT) is reported here to achieve the goal of cascade multistage cancer treatment. A thermally responsive amphiphilic copolymer is designed and then a CuS nanoparticles (NPs)-based carbon monoxide (CO) photoinduced release system and doxorubicin (Dox) are encapsulated to construct the nanomedicine. The large-sized nanomedicine can accumulate in tumors after long circulation in vivo and will generate heat to act as a photothermal therapeutic agent by near infrared (NIR) light. Moreover, synergically release of CO and Dox is achieved and acted as a sensitized chemotherapeutic agent. The combination of PTT and chemotherapy sensitization can effectively eliminate active tumor cells in the periphery of the tumor. CuS NPs are also released after the degradation of nanomedicine and small-sized CuS NPs possess better tumor penetration and achieve penetration-enhanced PTT by further NIR irradiation, thereby effectively eliminating tumor cells inside solid tumors. Hence, cascade multistage cancer treatment of "combined PTT and chemotherapy sensitization"-"penetration-enhanced PTT" is achieved, and tumor cells are comprehensively and effectively eliminated.

Neuromedin B receptor stimulation of Cav3.2 T-type Ca2+ channels in primary sensory neurons mediates peripheral pain hypersensitivity.

Background: Neuromedin B (Nmb) is implicated in the regulation of nociception of sensory neurons. However, the underlying cellular and molecular mechanisms remain unknown. Methods: Using patch clamp recording, western blot analysis, immunofluorescent labelling, enzyme-linked immunosorbent assays, adenovirus-mediated shRNA knockdown and animal behaviour tests, we studied the effects of Nmb on the sensory neuronal excitability and peripheral pain sensitivity mediated by Cav3.2 T-type channels. Results: Nmb reversibly and concentration-dependently increased T-type channel currents (IT) in small-sized trigeminal ganglion (TG) neurons through the activation of neuromedin B receptor (NmbR). This NmbR-mediated IT response was Gq protein-coupled, but independent of protein kinase C activity. Either intracellular application of the QEHA peptide or shRNA-mediated knockdown of Gß abolished the NmbR-induced IT response. Inhibition of protein kinase A (PKA) or AMP-activated protein kinase (AMPK) completely abolished the Nmb-induced IT response. Analysis of phospho-AMPK (p-AMPK) revealed that Nmb significantly activated AMPK, while AMPK inhibition prevented the Nmb-induced increase in PKA activity. In a heterologous expression system, activation of NmbR significantly enhanced the Cav3.2 channel currents, while the Cav3.1 and Cav3.3 channel currents remained unaffected. Nmb induced TG neuronal hyperexcitability and concomitantly induced mechanical and thermal hypersensitivity, both of which were attenuated by T-type channel blockade. Moreover, blockade of NmbR signalling prevented mechanical hypersensitivity in a mouse model of complete Freund's adjuvant-induced inflammatory pain, and this effect was attenuated by siRNA knockdown of Cav3.2. Conclusions: Our study reveals a novel mechanism by which NmbR stimulates Cav3.2 channels through a Gßγ-dependent AMPK/PKA pathway. In mouse models, this mechanism appears to drive the hyperexcitability of TG neurons and induce pain hypersensitivity.

Patient Engagement in Randomized Controlled Tai Chi Clinical Trials among the Chronically Ill.

BACKGROUND: Physicians encounter various symptom-based complaints each day. While physicians strive to support patients with chronic illnesses, evidence indicates that patients who are actively involved in their health care have better health outcomes and sometimes lowers costs. AIM: This article is to analyze how patient engagement is described when complex interventions such as Tai Chi were delivered in Randomized Controlled clinical Trials (RCTs). It reviews the dynamic patient- physician relationship in chronic illness management and to illustrate the patient engagement process, using Tai Chi as an example intervention. METHODS: RCTs are considered the gold standard in clinical research. This study is a qualitative analysis of RCTs using Tai Chi as an intervention. A systematic literature search was performed to identify quality randomized controlled clinical trials that investigated the effects of Tai Chi. Selected clinical trials were classified according to research design, intervention style, patient engagement, and outcomes. Patient engagement was classified based on levels of patient participation, compliance, and selfmanagement. The chronic health conditions included in this paper are Parkinson's disease, polyneuropathy, hypertension, stroke, chronic insomnia, chronic heart failure, fibromyalgia, osteoarthritis, central obesity, depression, deconditioning in the elderly, or being pre-clinically disabled. RESULTS AND CONCLUSION: We found that patient engagement, as a concept, was not well defined in literature. It covers a wide range of related terms, such as patient involvement, participation, shared decision- making, patient activation, adherence, compliance, and self-management. Tai Chi, as a very complex practice system, is to balance all aspects of a patient's life; however, the level of patient engagement is difficult to describe using conventional clinical trial design. To accurately illustrate the effect of a complex intervention, novel research design must explore ways to measure patient engagement in the intervention in order to clarify its specific role on health.

The Role of Tai Chi in Mental Health Management-Lessons Learned from Clinical Trials.

BACKGROUND: Many people seek alternative treatments to reduce stress and to manage anxiety. To counsel people appropriately, physicians need to understand current evidence and recognize both the value and defects in the facts. OBJECTIVE: To review the effect of Tai Chi interventions on improvement of mental health and to learn lessons from current evidence through various clinical studies. METHODS: A literature search was performed to identify research studies that assessed Tai Chi's mental health benefits. Selected studies were classified according to research design, outcome measures, and results. They were qualitatively assessed based on Tai Chi's significant influence on mental health in the areas of mood, stress, and anxiety level. RESULTS: After screening in citations that mentioned Tai Chi as an intervention, we found 21 clinical studies, all of which included at least one outcome measure of mental health or a testing system that included a mental health component. Our results show low evidence of recommending Tai Chi intervention to all patients who seek improvement in mental health despite that many positive effects of Tai Chi practice on mood and anxiety were found in different clinical trials. CONCLUSION: Considering the fact that Tai Chi is a gentle exercise, well suited for people with various physical capabilities, especially the elderly, health care providers may consider recommending it to people with mental health issues and seek alternative treatment besides routine medical care. Nonetheless, clinicians should be aware of the limitations due to incomplete understanding of Tai Chi as an intervention. Better evidence and stronger clinical trial designs are needed to further investigate Tai Chi's role in improving mental health.

Distribution of nutrients, heavy metals, and PAHs affected by sediment dredging in the Wujin'gang River basin flowing into Meiliang Bay of Lake Taihu.

This paper's survey of the pollution of the Wujin'gang River is important because it is one of the main rivers flowing into Meiliang Bay of Lake Taihu in eastern China. Trace metals (TMs) in this paper are described according to their pollution index (P i). Cluster analysis and correlation analysis are utilized for group sites and to assess co-contamination. Toxicity effect analysis was conducted using individual sediment quality guideline quotients (SQGQs) and mean SQGQs. The results showed that sediment from the Wujin'gang River basin was affected by nutrients, heavy metals, and polycyclic aromatic hydrocarbons (PAHs), which are an essential contamination source for both Meiliang Bay and Zhushan Bay of Lake Taihu. The discharge of TMs has significant correlations to total nitrogen (TN) and total phosphorus (TP); however, no significant correlations were observed between the content of PAHs and TMs. Toxicity effect results show that sediment in the Wujin'gang River basin threatens sediment-dwelling organisms. The harmful effect was mainly caused by heavy metals especially Cd, Cr, Ni, and Cu. Sediment dredging is an effective way to control pollution from internal rivers especially for the pollution of TN and heavy metals in the Wujin'gang River basin.