Self-Delivery Nanoplatform Based on Amphiphilic Apoptosis Peptide for Precise Mitochondria-Targeting Photothermal Therapy.

Mitochondria-targeting photothermal therapy could significantly enhance the tumor cell killing effect. However, since therapeutic reagents need to overcome a series of physiological obstacles to arrive at mitochondria accurately, precise mitochondria-targeting photothermal therapy still faces great challenges. In this study, we developed a self-delivery nanoplatform that specifically targeted the mitochondria of tumor cells for precise photothermal therapy. Photothermal agent IR780 was encapsulated by amphiphilic apoptotic peptide KLA with mitochondria-targeting ability to form nanomicelle KI by self-assembly through hydrophilic and hydrophobic interactions. Subsequently, negatively charged tumor-targeting polymer HA was coated on the surface of KI through electrostatic interactions, to obtain tumor mitochondria-targeting self-delivery nanoplatform HKI. Through CD44 receptor-mediated recognition, HKI was internalizated by tumor cells and then disassembled in an acidic environment with hyaluronidase in endosomes, resulting in the release of apoptotic peptide KLA and photothermal agent IR780 with mitochondria anchoring capacity, which achieved precise mitochondria guidance and destruction. This tumor mitochondria-targeting self-delivery nanoplatform was able to effectively deliver photothermal agents and apoptotic peptides to tumor cell mitochondria, resulting in precise destruction to mitochondria and enhancing tumor cell inhibition at the subcellular organelle level.

Advances of Photothermal Agents with Fluorescence Imaging/Enhancement Ability in the Field of Photothermal Therapy and Diagnosis.

Photothermal therapy (PTT) is an effective cancer treatment method. Due to its easy focusing and tunability of the irradiation light, direct and accurate local treatment can be performed in a noninvasive manner by PTT. This treatment strategy requires the use of photothermal agents to convert light energy into heat energy, thereby achieving local heating and triggering biochemical processes to kill tumor cells. As a key factor in PTT, the photothermal conversion ability of photothermal agents directly determines the efficacy of PTT. In addition, photothermal agents generally have photothermal imaging (PTI) and photoacoustic imaging (PAI) functions, which can not only guide the optimization of irradiation conditions but also achieve the integration of disease diagnosis. If the photothermal agents have function of fluorescence imaging (FLI) or fluorescence enhancement, they can not only further improve the accuracy in disease diagnosis but also accurately determine the tumor location through multimodal imaging for corresponding treatment. In this paper, we summarize recent advances in photothermal agents with FLI or fluorescence enhancement functions for PTT and tumor diagnosis. According to the different recognition sites, the application of specific targeting photothermal agents is introduced. Finally, limitations and challenges of photothermal agents with fluorescence imaging/enhancement in the field of PTT and tumor diagnosis are prospected.

Association between type of drinking water and upper gastrointestinal cancer incidence in the Linxian General Population.

BACKGROUND: This study aimed to explore the association between drinking water source and risk of upper gastrointestinal (UGI) cancer, including esophageal cancer (EC) and gastric cancer (GC), in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. METHODS: In this study, we used data from the Linxian NIT cohort, which included 29,584 healthy adults aged 40 to 69 years. Subjects were enrolled in April 1986 and followed up until March 2016. Tap water drinking status and demographic characteristics were collected at baseline. Subjects who drank tap water were treated as the exposed group. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model. RESULTS: A total of 5,463 cases of UGI cancer were identified during the 30-year follow-up period. After adjusting for multiple factors, the incidence rate of UGI cancer in participants who drank tap water was significantly lower compared with individuals in the control (HR = 0.91, 95% CI: 0.86-0.97). A similar association was observed between tap water drinking and EC incidence (HR = 0.89, 95% CI: 0.82-0.97). The association between drinking tap water and risk of UGI cancer and EC incidence did not vary across the subgroup by age and gender (All Pinteraction > 0.05). For EC incidence, an interaction effect was observed for riboflavin/niacin supplements and drinking water source (Pinteraction = 0.03). No association was observed between drinking water source and GC incidence. CONCLUSIONS: In this prospective cohort study in Linxian, participants who drank tap water had a lower risk of EC incidence. As a source of drinking water, use of tap water may reduce the risk of EC by avoiding exposure to nitrate/nitrite. Measures should be taken to improve the quality of drinking water in high-incidence areas of EC. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov (NCT00342654, 21/06/2006), and the trial name is Nutrition Intervention Trials in Linxian Follow-up Study.

Tibetan medicine Bang Jian: a comprehensive review on botanical characterization, traditional use, phytochemistry, and pharmacology.

Tibetan medicine Bang Jian refers to a range of botanical drugs within the Gentiana genus. It serves as a prominent traditional Tibetan botanical drug primarily found in the ethnic minority regions of the Qinghai-Tibet Plateau in China. Traditionally, the dried flowers of Bang Jian, known as "Longdanhua" have been employed in Tibetan medicine to address detoxification, pharyngeal relief, acute and chronic bronchitis, bronchiectasis, lung infections, pulmonary fibrosis, and throat disorders. Surprisingly, there has been no comprehensive review published to date on Tibetan medicine Bang Jian. This passage systematically presents and critically assesses recent advancements in botanical characterization, traditional applications, phytochemistry, pharmacology, and clinical uses of Bang Jian, aiming to provide a scientific foundation for its reasonable use and further exploration. To date, researchers have isolated and identified 92 structurally diverse compounds, with a predominant presence of iridoids, flavonoids, xanthones, and triterpenoids. The crude extracts and metabolites derived from Bang Jian have been found to exhibit a wide range of pharmacological effects, encompassing anti-inflammatory, anti-tumor, anti-bacterial, antiviral, antioxidant, hepatoprotective properties, and protect the respiratory system. Nevertheless, detailed data on the biological effects, metabolic activities, and mechanistic research concerning active monomer metabolites remain insufficient. Consequently, there is a pressing need for comprehensive and in-depth research to guide rational clinical drug usage and evaluate the medicinal attributes of Bang Jian.

Statins on Spontaneous Intracerebral Hemorrhage: A Meta-Analysis.

Objective: In order to explore whether the application of statins can improve the prognosis of patients with intracerebral hemorrhage. Methods: Studies of patients with intracerebral hemorrhage taking statins published in English until December 2021 were searched based on limited search terms, the retrieved literature was screened out based on inclusion and exclusion criteria, and the quality assessment and data extraction were carried out independently by two investigators. The extracted clinical data were then meta-analyzed. Results: A total of 17 literatures were included in this study, with a sample size of 16,988 cases, including 3,001 cases in the statin group and 13,487 cases in the control group. MRS score of mortality was used as the prognostic index to evaluate cerebral hemorrhage. According to the Newcastle-Ottawa Scale (NOS), the score of literature quality evaluation scale was 6-8, indicating good literature quality. Meta-analysis of clinical data extracted from the literature showed that the statin group reduced overall mortality after intracerebral hemorrhage compared with the nonstatin group (P < 0.01). In terms of improving functional prognosis, the statin group improved functional prognosis 90 days after intracerebral hemorrhage (P=0.01). There was no significant difference between the statin and nonstatin groups in reducing the number of intracerebral hematomas. Conclusions: Statins can reduce the total mortality after ICH and improve the survival rate (90 d), without increasing the amount of hematoma.

Mortality after multivitamin supplementation: Nearly 35-year follow-up of the randomized Linxian Dysplasia Nutrition Intervention Trial.

BACKGROUND: The objective of this study was to update the association between multivitamin supplementation and total or cause-specific mortality in a population with a high prevalence of undernutrition in China. METHODS: The Linxian Dysplasia Nutrition Intervention Trial was a randomized, double-blind, placebo-controlled trial in which 3318 persons aged 40-69 years with esophageal squamous dysplasia were assigned to receive daily multivitamin supplementation or a placebo for 6 years and were followed for 29 years. The primary outcome was esophageal/gastric cardia cancer mortality. The data were analyzed with Cox proportional hazards regression models. Subgroup analyses were performed by common characteristics such as age and gender. RESULTS: The cumulative total mortality was 83.5%. Multivitamin supplementation did not affect total or cause-specific mortality in the participants as a whole (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.89-1.03). Subgroup analyses showed that no association between multivitamin supplementation and all-cause mortality was observed in men (HR, 0.90; 95% CI, 0.81-1.01), women (HR, 1.01; 95% CI, 0.91-1.12), younger participants (HR, 0.97; 95% CI, 0.87-1.08), or older participants (HR, 0.94; 95% CI, 0.85-1.04). Significant reductions in heart disease mortality (HR, 0.64; 95% CI, 0.47-0.87) and cerebrovascular disease mortality (HR, 0.74; 95% CI, 0.56-1.00) were seen in older men. In a subgroup of younger men and a subgroup of moderate or severe dysplasia, subjects receiving multivitamin supplementation had a lower risk of esophageal/cardia cancer mortality (HR for younger men, 0.76; 95% CI, 0.58-0.99; HR for moderate or severe dysplasia, 0.76; 95% CI, 0.58-1.00). No association between multivitamin supplementation and any cause-specific mortality was observed in a mild dysplasia population. CONCLUSIONS: Multivitamin supplementation in a population with esophageal squamous dysplasia was not associated with the risk of total mortality in the 35-year follow-up of this randomized controlled trial. In light of this and previous trials, multivitamin supplements should be used thoughtfully to improve health status of populations with esophageal squamous dysplasia. LAY SUMMARY: Multivitamin supplementation is common, yet its effect on mortality is unclear. The aim of this study was to update the long-term effects of multivitamin supplementation on total and cause-specific mortality during nearly 35 years of follow-up in the Linxian Dysplasia Nutrition Intervention Trial in China. Multivitamin supplementation in a population with esophageal squamous dysplasia was not associated with the risk of total mortality in the 35-year follow-up of this randomized controlled trial, and this indicates that multivitamin supplements should be used thoughtfully to improve health status.

The therapeutic effect of Xuanbai Chengqi Decoction on chronic obstructive pulmonary disease with excessive heat in the lung and fu-organs based on gut and lung microbiota as well as metabolic profiles.

As a prescription for treating lung inflammation and intestinal diseases, Xuanbai Chengqi Decoction (XBCQD) in clinical practice can effectively treat COPD with excessive heat in the lung and fu-organs, which is characterized by phlegm-heat accumulation in the lung and constipation. This study aims to find the potential biomarkers of COPD with excessive heat in the lung and fu-organs from two aspects of lung and intestine based on metabolomics and microbiota analysis, and to evaluate the efficacy of XBCQD as well as to explore the mechanism of drug function according the regulating effect of drugs on these markers. The HPLC-Q-TOF-MS/MS, 16SrDNA technology and multiple statistical methods were used to trace the process of disease and curative effect with XBCQD. Results showed that the onset and development of disease was associated with the imbalance of 41 differential metabolites in plasma, bronchoalveolar lavage fluid and feces and 82 bacteria at the levels of phylum, class, order, family and genus from lung and intestine, including Escherichia-Shigella. However, after treatment with XBCQD, 30 differential metabolites mainly involving in the metabolism of linoleic acid, taurine and hypotaurine metabolism, arachidonic acid metabolism, biosynthesis of primary bile acids, tryptophan metabolism, arginine and proline metabolism and 65 pulmonary and intestinal bacteria at all levels were reversed in the drug group. In addition, the results of the correlation analysis showed that specific microbiota from lung and intestine and reversed differential metabolites had a significant correlation, and they could affect each other in the course of disease occurrence and treatment. This study preliminarily confirmed that XBCQD can be used to treat COPD with excessive heat in the lung and fu-organs through lung-intestine simultaneous treatment. It also provided new strategies for the treatment of lung diseases or intestinal diseases, and new research ideas for the evaluation of drug efficacy.

[Preparation and intestinal absorption of Panax notoginseng saponins chitosan nanoparticles].

In this experiment, Panax notoginseng saponins chitosan nanoparticles(PNS-NPs) were prepared by self-assembly and their appearance, particle size, encapsulation efficiency, drug loading, polydispersity index(PDI), Zeta potential, and microstructure were characterized. The prepared PNS-NPs were intact in structure, with an average particle size of(209±0.258) nm, encapsulation efficiency of 42.34%±0.28%, a drug loading of 37.63%±0.85%, and a Zeta potential of(39.8±3.122) mV. The intestinal absorption of PNS-NPs in rats was further studied. The established HPLC method of PNS was employed to investigate the effects of pH, perfusion rate, and different drugs(PNS raw materials, Xuesaitong Capsules, and PNS-NPs). The absorption rate constant(K_a) and apparent permeability coefficient(P_(app)) in the duodenum, jejunum, ileum, and colon were calculated and analyzed. As illustrated by the results, the intestinal absorption of PNS-NPs was increased in the perfusion solution at pH 6.8(P<0.05), and perfusion rate had no significant effect on the K_a and P_(app) of PNS-NPs. The intestinal absorption of PNS-NPs was significantly different from that of PNS raw materials and Xuesaitong Capsules(P<0.05), and the intestinal absorption of PNS-NPs was significantly improved.

Effects of traditional Chinese medicine collaborative model (TCMCM) combined with adjuvant chemotherapy on IIIb and IIIc gastric cancer: a protocol for a randomized controlled trial.

BACKGROUND: Metastasis and/or recurrence can decrease the survival time of gastric cancer patients undergoing radical operation. Among them, those with stage IIIb and IIIc are especially at a high risk of metastasis and recurrence. The traditional Chinese medicine collaborative model (TCMCM) has been used in the treatment of cancer; however, its effects have not been systematically evaluated. This study is designed to evaluate whether TCMCM can decrease adverse effects after chemotherapy and reduce the recurrence and metastasis of stage IIIb and IIIc gastric cancer. METHODS/DESIGN: This prospective, multicenter, randomized, open-label trial will recruit 260 patients with stage IIIb and IIIc gastric cancer who undergo radical surgery for D2 lymphadenectomy. The patients will be randomly assigned to receive usual adjuvant chemotherapy and TCMCM (intervention group) in a 1:1 ratio. Patients in the intervention group will receive an oral traditional Chinese formula, auricular acupressure, and acupoint therapy. All participants will receive usual adjuvant chemotherapy. The primary outcome is a 3-year disease-free survival rate. Secondary outcomes include quality of life, side effects caused by chemotherapy, and safety-related measures. Assessments will be performed during the screening period, at 4 and 8 cycles after adjuvant chemotherapy, and 9, 12, 18, 24, 30, and 36 months after randomization. Adverse events will be recorded. In addition, biological samples will be collected for mechanism analysis. DISCUSSION: This will be the first clinical trial to evaluate the effects of TCMCM on disease-free survival (DFS) and quality of life in patients with stage IIIb and IIIc gastric cancer. Our results may be used to standardize TCMCM. We will also perform a larger-scale clinical trial in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT03607656 . Registered on 1 July 2018. The final protocol version is V1.1.

Enhanced interoceptive attention mediates the relationship between mindfulness training and the reduction of negative mood.

Although accumulating evidence has revealed the effect of mindfulness training on the reduction of general stress and the improvement of mental well-being, the underlying mechanism remains unclear. In this study, we investigated whether interoceptive attention to respiratory signals plays a role. Healthy adults were randomly assigned to either receive an 8-week mindfulness training (n = 29) or inactive control (n = 28). The pre- and post-training self-reported states of negative mood were assessed together with an objective measure of interoceptive attention to respiration. Compared to the control group, mindfulness training led to a decrease in the level of negative mood and an increase in interoceptive sensitivity. Mediation analysis further showed that the effect of mindfulness training on the reduction of negative mood was fully mediated by increased interoceptive sensitivity. These results suggest that mindfulness training effectively alleviates negative mood by enhancing interoceptive attention to respiratory signals.

Integrating network pharmacology deciphers the action mechanism of Zuojin capsule in suppressing colorectal cancer.

BACKGROUND AND PURPOSE: Zuojin capsule (ZJC), a classical prescription, is outstanding in improving the conditions of patients with gastrointestinal diseases and colorectal cancer (CRC). Although ZJC has multi-ingredient and multi-target characteristics, its pharmacological effect on colorectal cancer and the underlying mechanism remain unclear. METHOD: Here, the activity of ZJC against CRC was evaluated by the experiments with CRC cells and HCT-116 xenografted mice. The key genes of CRC were obtained from the cancer genome atlas (TCGA). The genes potentially targeted by ZJC were collected from traditional Chinese medicine systems pharmacology (TCMSP) database. The underlying pathways related to selected targets were analyzed through gene ontology (GO) and pathway enrichment analyses. Western blot (WB), cellular thermal shift assay (CETSA), molecular docking and quantitative real-time PCR (QRT-PCR) were carried out to confirm the validity of the targets. RESULTS: In vitro and in vivo results indicated that ZJC may inhibit CRC cells and tumor growth. The network pharmacological analysis indicated that 22 compounds, 51 targets and 20 pathways were involved in the compound-target-pathway network. Our results confirmed that ZJC inhibited cycle progression, migration and induced apoptosis by targeting candidate genes (CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2, and MMP9). We found that ZJC could directly change the protein level by regulating the protein stability and transcriptional activity of the target. CONCLUSIONS: In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. The results of this study provide a basic theory for the clinical trials of Zuojin Capsules against colorectal cancer.

Colorectal cancer in the Linxian China Nutrition Intervention Trial: Risk factors and intervention results.

BACKGROUND: Colorectal cancer (CRC) is among the most common cancers in economically developed countries and developing world. While dietary factors are associated with risk of CRC in the West and urban China, little is known about risk or protective factors in rural China. METHODS: The Linxian General Population Nutrition Intervention Trial (NIT) cohort was established over 30 years ago to test whether daily multivitamin/mineral supplements could reduce the incidence and mortality of esophageal/gastric cardia cancer. The cohort included a total of 29,553 healthy participants 40-69 years old who were randomly assigned to supplements or placebos via a 24 fractional factorial study design. We examined risk factors for the development of CRC as well as the effects of four different nutritional factors (Factor A: retinol, zinc; B: riboflavin, niacin; C: ascorbic acid, molybdenum; D: selenium, alpha-tocopherol, beta-carotene,) on CRC incidence following 5.25 years of supplementation in this randomized, placebo-controlled intervention trial. RESULTS: CRC risk increased with age and height as well as piped water usage, family history of CRC, and consumption of foods cooked in oil, eggs, and fresh fruits. No effect on CRC was seen for any of these four intervention factors tested in both genders, but CRC was reduced 37% in females who received Factor D (selenium/alpha-tocopherol/beta-carotene) (RR = 0.63, 95% CI = 0.43-0.92, P = 0.016) compared to females who did not receive Factor D. CONCLUSIONS: In this undernourished rural Chinese population, CRC risk factors in this Chinese cohort showed both similarities and differences compared to Western and urban Asian Chinese populations. Intervention results suggested a potential benefit for women supplemented with selenium/alpha-tocopherol/beta-carotene.

Activation of the cognitive control network associated with information uncertainty.

The cognitive control network (CCN) that comprises regions of the frontoparietal network, the cingulo-opercular network, and other sub-cortical regions as core structures is commonly activated by events with an increase in information uncertainty. However, it is not clear whether this CCN activation is associated with both information entropy that represents the information conveyed by the context formed by a sequence of events and the surprise that quantifies the information conveyed by a specific type of event in the context. We manipulated entropy and surprise in this functional magnetic resonance imaging study by varying the probability of occurrence of two types of events in both the visual and auditory modalities and measured brain response as a function of entropy and surprise. We found that activation in regions of the CCN increased as a function of entropy and surprise in both the visual and auditory tasks. The frontoparietal network and additional structures in the CCN mediated the relationship between these information measures and behavioral response. These results suggest that the CCN is a high-level modality-general neural entity for the control of the processing of information conveyed by both context and event.

A Protocol of a Guideline to Establish the Evidence Ecosystem of Acupuncture.

This is a protocol for developing a guideline to establish the evidence ecosystem of acupuncture. It describes all steps that will be followed in line with the World Health Organization Handbook for Guideline Development and the Reporting Items for practice Guidelines in Healthcare (RIGHT). The key steps included guideline protocol development, guideline registration, systematic review of acupuncture evidence issues, systematic review of methods for establishing evidence ecosystem, survey of acupuncture stakeholders regarding potential acupuncture evidence issues, development of potential items for guidelines, Delphi method for guideline item development, consensus meeting, drafting guideline, peer review, approval, and publishing. This future guideline will help to establish evidence ecosystem of acupuncture, which will facilitate the application of acupuncture in clinical practice.

Effects of Ginkgo biloba on Early Decompression after Spinal Cord Injury.

Spinal cord injury (SCI) is a severe trauma of the central nervous system characterized by high disability and high mortality. Clinical progress has been achieved in understanding the pathological mechanism of SCI and its early treatment, but the results are unsatisfactory. In China, increasing attention has been paid to the role of traditional Chinese medicine in the treatment of SCI. In particular, extracts from the leaves of Ginkgo biloba (maidenhair tree), which have been reported to exert anti-inflammatory and antioxidant properties and repair a variety of active cellular damage, have been applied therapeutically for centuries. In this study, we established a rat SCI model to investigate the effects of Ginkgo biloba leaves on decompression at different stages of SCI. The application of Ginkgo biloba leaves during the decompression of SCI at different time points, the neurological recovery of SCI, and the underlying molecular mechanism were explored. The findings provide reliable experimental data that reveal the mechanism of GBI (Ginkgo biloba injection) in the clinical treatment of SCI.

A multi-functional drug delivery system based on polyphenols for efficient tumor inhibition and metastasis prevention.

Although chemotherapy is the most common method in clinical therapeutics with a straightforward mechanism, conventional anti-tumor drugs are still almost incapable of preventing the occurrence of tumor metastasis. In this study, we developed a multi-functional drug delivery system EINP@DOX consisting of a tea-derived polyphenol EGCG, iron ions and DOX. The system integrated the functions of tumor inhibition, diagnosis and metastasis prevention to achieve a systematic tumor treatment. The nanoscale size of EINP@DOX facilitated its accumulation in tumor tissues by means of the enhanced permeability and retention (EPR) effect, and it was then transferred to endosomes. The weakly acidic microenvironment in the endosomes of the tumor cells could destroy the coordination structure of EINP@DOX to realize the release of DOX for tumor therapy. Furthermore, the dissociative EGCG played the role of an adjuvant to restrain EMT and down-regulate the MMP levels, which could prevent the occurrence of tumor metastasis. Meanwhile, iron ions as superior magnetic resonance imaging (MRI) contrast agents provided visual evidence for the accurate location of EINP@DOX. In vitro and in vivo studies demonstrated that EINP@DOX showed a remarkable performance in tumor diagnosis and excellent therapeutic efficacy, inhibiting the metastasis of tumor cells effectively at the same time.

Effect of glutenin and gliadin modified by protein-glutaminase on retrogradation properties and digestibility of potato starch.

The glutenin (Glu) and gliadin (Gli) were modified by protein-glutaminase (PG) to obtain soluble glutenin (PG-Glu) and gliadin (PG-Gli), and PG-Glu or PG-Gli was added to potato starch (PS) according to different amounts (0.5%, 1.0%, and 1.5%, based on dry starch weight, w/w) to explore the effect of modified proteins on the retrogradation behavior and digestibility of PS. The results showed that the long-term retrogradation of PS was accelerated by the addition of PG-Glu or PG-Gli. The addition of PG-Glu or PG-Gli led to an increase in hydrogen bonds within starch molecules and induced a significant increase in resistant starch content. The hydrolysis kinetic parameters, C∞ and K, both decreased with the increasing level of modified protein, indicating the deceleration of hydrolysis rate by the addition of PG-Glu or PG-Gli. In summary, the addition of PG-Glu or PG-Gli could promote the retrogradation of PS and mitigate the digestion of starch.

A tungsten nitride-based degradable nanoplatform for dual-modal image-guided combinatorial chemo-photothermal therapy of tumors.

An innovative tungsten-based multifunctional nanoplatform composed of polyethylene glycol (PEG)-modified tungsten nitride nanoparticles (WN NPs) is constructed for tumor treatment. The PEG-WN NPs not only possess strong near-infrared (NIR) absorbance, high photothermal conversion efficiency, and excellent photothermal stability, but also effectively inhibit tumor cells upon 808 nm laser irradiation. After coating with thiolated (2-hydroxypropyl)-ß-cyclodextrin (MUA-CD) on the surface, such a nanoplatform can also be used for drug delivery (such as DOX) and presents a synergistic tumor inhibition effect both in vitro and in vivo. Furthermore, the PEG-WN NPs present good contrasting capability for X-ray computed tomography (CT) and photoacoustic (PA) imaging. With PA/CT imaging, the tumor can be accurately positioned for precise treatment. It is worth mentioning that PEG-WN NPs are biodegradable and could be effectively excreted from the body with no appreciable toxicity in vivo. It is expected that this biocompatible multifunctional nanoplatform can serve as a potential candidate for tumor treatment in future clinical applications.

Association of tooth loss with liver cancer incidence and chronic liver disease mortality in a rural Chinese population.

BACKGROUND: Tooth loss has been reported to be associated with the risk of liver cancer in several prior studies in economically advantaged countries. Whether this relationship is also evident in economically disadvantaged populations is not known. METHODS: We analyzed data from the Nutrition Intervention Trials, two randomized placebo-controlled trials of vitamin/mineral supplementation in Linxian, China. Participants who reported having lost permanent teeth were examined to determine the number of teeth remaining. In the 30-year follow-up period, 329 liver cancers were diagnosed and 368 chronic liver disease deaths occurred. Tooth loss was categorized based on loess smoothed age-specific predicted quartiles. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the two outcomes. RESULTS: Overall, persons in the highest quartile of age-specific tooth loss had an increased risk of liver cancer (HR = 1.27, 95%CI: 0.96, 1.67) which was not statistically significant. Results varied by sex and body mass index (BMI), however. Women in the highest quartile of age-specific tooth loss had a significantly increased risk (HR = 1.64, 95%CI: 1.04, 2.59), while men did not (HR = 1.08, 95%CI = 0.75, 1.57), and persons with a BMI > 23.0 kg/m2 (HR = 1.71, 95%CI: 1.00, 2.92) had a significantly increased risk, while persons with a BMI <23.0 kg/m2 did not (HR = 1.14, 95%CI: 0.82, 1.5). No relationships with chronic liver disease mortality were observed. CONCLUSIONS: In a rural, economically disadvantaged population, persons with the highest levels of age-specific tooth loss had an increased risk of liver cancer. The results, which were stronger among women and persons with greater BMI, suggest that periodontal disease may increase risk of liver cancer.

Normalizing Tumor Microenvironment Based on Photosynthetic Abiotic/Biotic Nanoparticles.

Tumor hypoxia has attained the status of a core hallmark of cancer that globally affects the entire tumor phenotype. Reversing tumor hypoxia might offer alternative therapeutic opportunities for current anticancer therapies. In this research, a photosynthetic leaf-inspired abiotic/biotic nano-thylakoid (PLANT) system was designed by fusing the thylakoid membrane with synthetic nanoparticles for efficient O2 generation in vivo. Under 660 nm laser irradiation, the PLANT system exhibited intracellular O2 generation and the anaerobic respiration of the multicellular tumor spheroid was suppressed by PLANT as well. In vivo, it was found that PLANT could not only normalize the entire metabolic network but also adjust the abnormal structure and function of the tumor vasculature. It was demonstrated that PLANT could significantly enhance the efficacy of phototherapy or antiangiogenesis therapy. This facile approach for normalizing the tumor microenvironment will find great potential in tumor therapy.