Fused Azulenyl Squaraine Derivatives Improve Phototheranostics in the Second Near-Infrared Window by Concentrating Excited State Energy on Non-Radiative Decay Pathways.

The second near-infrared (NIR-II) theranostics offer new opportunities for precise disease phototheranostic due to the enhanced tissue penetration and higher maximum permissible exposure of NIR-II light. However, traditional regimens lacking effective NIR-II absorption and uncontrollable excited-state energy decay pathways often result in insufficient theranostic outcomes. Herein a phototheranostic nano-agent (PS-1 NPs) based on azulenyl squaraine derivatives with a strong NIR-II absorption band centered at 1092 nm is reported, allowing almost all absorbed excitation energy to dissipate through non-radiative decay pathways, leading to high photothermal conversion efficiency (90.98 %) and strong photoacoustic response. Both in vitro and in vivo photoacoustic/photothermal therapy results demonstrate enhanced deep tissue cancer theranostic performance of PS-1 NPs. Even in the 5 mm deep-seated tumor model, PS-1 NPs demonstrated a satisfactory anti-tumor effect in photoacoustic imaging-guided photothermal therapy. Moreover, for the human extracted tooth root canal infection model, the synergistic outcomes of the photothermal effect of PS-1 NPs and 0.5 % NaClO solution resulted in therapeutic efficacy comparable to the clinical gold standard irrigation agent 5.25 % NaClO, opening up possibilities for the expansion of NIR-II theranostic agents in oral medicine.

Targeted delivery of organic small-molecule photothermal materials with engineered extracellular vesicles for imaging-guided tumor photothermal therapy.

Imaging-guided photothermal therapy (PTT) for cancers recently gathered increasing focus thanks to its precise diagnosis and potent therapeutic effectiveness. Croconaine (CR) dyes demonstrate potential in expanding utility for near infrared (NIR) dyes in bio-imaging/theranostics. However, reports on CR dyes for PTT are scarce most likely due to the short of the efficacious delivery strategies to achieve specific accumulation in diseased tissues to induce PTT. Extracellular vesicles (EVs) are multifunctional nanoparticle systems that function as safe platform for disease theragnostics, which provide potential benefits in extensive biomedical applications. Here, we developed a novel delivery system for photothermal molecules based on a CR dye that exerts photothermal activity through CDH17 nanobody-engineered EVs. The formed CR@E8-EVs showed strong NIR absorption, excellent photothermal performance, good biological compatibility and superb active tumor-targeting capability. The CR@E8-EVs can not only visualize and feature the tumors through CR intrinsic property as a photoacoustic imaging (PAI) agent, but also effectively retard the tumor growth under laser irradiation to perform PTT. It is expected that the engineered EVs will become a novel delivery vehicle of small organic photothermal agents (SOPTAs) in future clinical PTT applications.

Chemical profiling and investigation of molecular mechanisms underlying anti-hepatocellular carcinoma activity of extracts from Polygonum perfoliatum L.

Polygonum perfoliatum L. is an herbal medicine that has been extensively used in traditional Chinese medicine to treat various health conditions ranging from ancient internal to surgical and gynecological diseases. Numerous studies suggest that P. perfoliatum extract elicits significant anti-tumor, anti-inflammatory, anti-bacterial, and anti-viral effects. Nevertheless, the underlying mechanisms of its anti-liver cancer effects remain poorly understood. Our study suggests that P. perfoliatum stem extract (PPLA) has a favorable safety profile and exhibits a significant anti-liver cancer effect both in vitro and in vivo. We identified that PPLA activates the cGMP-PKG signaling pathway, and key regulatory genes including ADRA1B, PLCB2, PRKG2, CALML4, and GLO1 involved in this activation. Moreover, PPLA modulates the expression of genes responsible for the cell cycle. Additionally, we identified four constituents of PPLA, namely taxifolin, myricetin, eriodictyol, and pinocembrin, that plausibly act via the cGMP-PKG signaling pathway. Both in vitro and in vivo experiments confirmed that PPLA, along with its constituting compounds taxifolin, myricetin, and eriodictyol, exhibit potent anti-cancer activities and hold the promise of being developed into therapeutic agents.

Association of vitamin D in individuals with periodontitis: an updated systematic review and meta-analysis.

BACKGROUND: There are differences in vitamin D levels between periodontitis and healthy individuals, but the effect of vitamin D on periodontitis is controversial. The purpose of this Meta-analysis is twofold: (1) compare vitamin D levels in individuals with or without periodontitis; (2) assess the effects of vitamin D supplementation during scaling and root planing (SRP) on periodontal clinical parameters in individuals with periodontitis. METHODS: A systematic search was conducted in five databases (PubMed, Web of Science, MEDLINE, EMBASE, and Cochrane library), published from the database inception to 12 September 2022. The Cochrane Collaboration Risk of bias (ROB) assessment tool, the risk of bias in non-randomized studies of intervention (ROBINS-I) tool, the Newcastle-Ottawa Quality Assessment Scale (NOS), and Agency for Healthcare Quality and Research (AHRQ) were used to evaluate randomized controlled trial (RCT), non-RCT, case-control study, and cross-sectional study, respectively. Statistical analysis was performed using RevMan 5.3 and Stata 14.0 software, with weighted mean difference (WMD), standardized mean difference (SMD) and 95% confidence intervals (CI) as the effect measures, and heterogeneity was tested by subgroup analysis, sensitivity analysis, Meta-regression. RESULTS: A total of 16 articles were included. The results of Meta-analysis showed that periodontitis was associated with lower serum vitamin D levels compared to normal population (SMD = -0.88, 95%CI -1.75 ~ -0.01, P = 0.048), while there was no significant difference in serum or saliva 25(OH)D levels between periodontitis and normal population. Additionally, the Meta-analysis showed that SRP + vitamin D and SRP alone had a statistically significant effect on serum vitamin D levels in individuals with periodontitis (SMD = 23.67, 95%CI 8.05 ~ 32.29, P = 0.003; SMD = 1.57, 95%CI 1.08 ~ 2.06, P < 0.01). And SRP + vitamin D could significantly reduce clinical attachment level compared to SRP alone (WMD = -0.13, 95%CI -0.19 ~ -0.06, P < 0.01), but had no meaningful effect on probing depth, gingival index, bleeding index, respectively. CONCLUSION: The evidence from this Meta-analysis suggests that the serum vitamin D concentration of individuals with periodontitis is lower than that of normal people, and SRP along with vitamin D supplementation has been shown to play a significant role in improving periodontal clinical parameters. Therefore, vitamin D supplementation as an adjuvant to nonsurgical periodontal therapy has a positive impact on the prevention and treatment of periodontal disease in clinical practice.

Chinese herbal medicines for treating ulcerative colitis via regulating gut microbiota-intestinal immunity axis.

Ulcerative colitis (UC) is one of types of inflammatory bowel disease with high recurrence. Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC. Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC. Many Chinese herbal medicines including some of single herb, herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity. Some clinical trials have shown promising results. This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity. The existing clinical trials are also summarized.

Emodin, a Natural Anthraquinone, Increases Uric Acid Excretion in Rats with Potassium Oxonate-Induced Hyperuricemia.

The treatment of hyperuricemia and gout is mostly based on lowering serum uric acid levels using drugs, such as allopurinol, or increasing urinary excretion of uric acid. However, some patients still experience adverse reactions to allopurinol and turn to Chinese medicine as an alternative. Therefore, it is crucial to design a preclinical study to obtain more convincing data on the treatment of hyperuricemia and gout with Chinese medicine. This study aimed to explore the therapeutic effect of emodin, a Chinese herbal extract, in a rat model of hyperuricemia and gout. In this study, we used 36 Sprague-Dawley rats, which were randomly divided into six groups for experimentation. Hyperuricemia was induced in rats by intraperitoneal injections of potassium oxonate. The efficacy of emodin in reducing serum uric acid levels was demonstrated by comparing the positive control group with groups treated with three different concentrations of emodin. The inflammatory profiles, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α levels, were unaffected by emodin treatment. In the experimental results, it was observed that the serum uric acid concentration in the vehicle control group was 1.80 ± 1.14, while the concentrations in the moderate and high concentration emodin groups were 1.18 ± 0.23 and 1.12 ± 0.57, resulting in no significant difference in uric acid concentration between these treatment groups and the control group, indicating that emodin has a therapeutic effect on hyperuricemia. The increase in the fractional excretion of uric acid (FEUA) demonstrated that emodin promoted urinary uric acid excretion without significantly affecting the inflammatory profile. Thus, emodin reduced the serum uric acid concentration to achieve effective treatment of hyperuricemia and gout by increasing urinary excretion. These results were supported by the measured serum uric acid and FEUA levels. Our data have potential implications for the treatment of gout and other types of hyperuricemia in clinical practice.

Effects of Tuina Combined With Moxibustion on Breast Cancer-Related Lymphedema: A Randomized Cross-Over Controlled Trial.

The objective of this study is to evaluate the effect of Tuina combined with moxibustion on relieving breast cancer-related lymphedema (BCRL). A randomized cross-over controlled trial was conducted at our institution. All patients with BCRL were assigned to 2 groups: Group A and Group B. In the first period (weeks 1-4), tuina and moxibustion were performed in Group A and pneumatic circulation and compression garment in Group B. The washout period took place from weeks 5 to 6. In the second period (weeks 7-10), pneumatic circulation and compression garment were performed in Group A, and tuina and moxibustion in Group B. Therapeutic efficacy was evaluated by measuring the affected arm volume, circumference, and Visual Analog Scale for swelling. Regarding the results, a total of 40 patients were included, and 5 cases were dropped. After treatment, both the traditional Chinses medicine (TCM) treatment and complete decongestive therapy (CDT) was found to reduce the volume of the affected arm (P < .05). At the endpoint (visit 3), compared with CDT, the effect of the TCM treatment was more evident than that of CDT (P < .05). After the TCM treatment, the arm circumference at the elbow crease and proximal 10 cm to elbow crease was reduced, which was statistically different from that before treatment (P < .05). Post-CDT treatment, the arm circumference at proximal 10 cm to wrist crease and the elbow crease and proximal 10 cm to elbow crease decreased, which was statistically different from that before treatment (P < .05). At the endpoint (visit 3), the arm circumference at proximal 10 cm to elbow crease of the patients treated with TCM was less than that of CDT (P < .05). Moreover, the VAS scores for swelling were better after compared with before TCM treatment and CDT (P < .05). At the endpoint (visit 3), the subjective relief of swelling by TCM treatment was greater than CDT (P < .05). Ultimately, tuina combined with moxibustion can alleviate BCRL symptoms, which is primarily reflected in reducing the affected arm volume and circumference and relieving swelling.Trial registration: Chinese Clinical Trial Registry (Registration Number ChiCTR1800016498).

Biodegradation of petroleum hydrocarbons based pollutants in contaminated soil by exogenous effective microorganisms and indigenous microbiome.

Microbial remediation is an eco-friendly and promising approach for the restoration of sites contaminated by petroleum hydrocarbons (PHCs). The degradation of total petroleum hydrocarbons (TPHs), semi volatile organic compounds (SVOCs) and volatile organic compounds (VOCs) of the soil samples collected from a petrochemical site by indigenous microbiome and exogenous microbes (Saccharomyces cerevisiae ATCC 204508/S288c, Candida utilis AS2.281, Rhodotorula benthica CBS9124, Lactobacillus plantarum S1L6, Bacillus thuringiensis GDMCC1.817) was evaluated. Community structure and function of soil microbiome and the mechanism involved in degradation were also revealed. After bioremediation for two weeks, the concentration of TPHs in soil samples was reduced from 17,800 to 13,100 mg/kg. The biodegradation efficiencies of naphthalene, benzo[a]anthracene, benzo[b]fluoranthene, benzo[a]pyrene, indeno[1,2,3-cd]pyrene, dibenzo[a,h]anthracene, 1,2,3-trichloropropane, 1,2-dichloropropane, ethylbenzene and benzene in soil samples with the addition of S. cerevisiae were 38.0%, 35.7%, 36.2%, 40.4%, 33.6%, 36.2%, 12.0%, 43.9%, 43.3% and 43.0%, respectively. The microbial diversity and community structure were improved during the biodegradation process. S. cerevisiae supplemented soil samples exhibited the highest relative abundance of the genus Acinetobacter for bacteria and Saccharomyces for yeast. The findings offer insight into the correlation between microbes and the degradation of PHC-based pollutants during the bioremediation process.

Therapeutic prospects of ceRNAs in COVID-19.

Since the end of 2019, COVID-19 caused by SARS-CoV-2 has spread worldwide, and the understanding of the new coronavirus is in a preliminary stage. Currently, immunotherapy, cell therapy, antiviral therapy, and Chinese herbal medicine have been applied in the clinical treatment of the new coronavirus; however, more efficient and safe drugs to control the progress of the new coronavirus are needed. Long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) may provide new therapeutic targets for novel coronavirus treatments. The first aim of this paper is to review research progress on COVID-19 in the respiratory, immune, digestive, circulatory, urinary, reproductive, and nervous systems. The second aim is to review the body systems and potential therapeutic targets of lncRNAs, miRNAs, and circRNAs in patients with COVID-19. The current research on competing endogenous RNA (ceRNA) (lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA) in SARS-CoV-2 is summarized. Finally, we predict the possible therapeutic targets of four lncRNAs, MALAT1, NEAT1, TUG1, and GAS5, in COVID-19. Importantly, the role of PTEN gene in the ceRNA network predicted by lncRNA MALAT1 and lncRNA TUG1 may help in the discovery and clinical treatment of effective drugs for COVID-19.

First Discovery of Beta-Sitosterol as a Novel Antiviral Agent against White Spot Syndrome Virus.

The outbreak of white spot syndrome (WSS) is a looming challenge, due to dramatic losses to the crustacean aquaculture industry. However, at present, there are no prophylactic or therapeutic means to control this infectious viral disease. Here, we screened fifteen medicinal plants for their inhibitory activity on the white spot syndrome virus (WSSV), using red swamp crayfish (Procambarus clarkii) as a model species. The results showed that the crude extracts of Pinellia ternata (Thunb.) Breit. had the highest inhibitory effect (91.59%, 100 mg/kg) on WSSV proliferation, and its main component, beta-sitosterol, showed a much higher activity (95.79%, 50 mg/kg). Further, beta-sitosterol potently reduced (p < 0.01) viral loads and viral gene transcription levels in a concentration-dependent fashion, and significantly promoted the survival rate of WSSV-challenged crayfish (57.14%, 50 mg/kg). The co-incubation assay indicated that beta-sitosterol did not influence the infectivity of WSSV particles. Both pre- and post-treatment of beta-sitosterol exerted a significant inhibitory effect (p < 0.01) on the viral load in vivo. Mechanistically, beta-sitosterol not only interfered with the expression of viral genes (immediate early gene 1, ie1; DNA polymerase, DNApol) that are important in initiating WSSV transcription, but it also attenuated the hijacking of innate immune signaling pathways (Toll, IMD, and JAK/STAT pathways) by viral genes to block WSSV replication. Moreover, the expression of several antiviral immune, antioxidant, pro-inflammatory, and apoptosis-related genes changed significantly in beta-sitosterol-treated crayfish. Beta-sitosterol is a potent WSSV inhibitor and has the potential to be developed as an effective anti-WSSV agent against a WSS outbreak in crustacean aquaculture.

Effects of Xinjiang wild cherry plum (Prunus divaricata Ledeb) anthocyanin-rich extract on the plasma metabolome of atherosclerotic apoE-deficient mice fed a high-fat diet.

It is well-known that many vegetables and fruits have abundant polyphenols, such as anthocyanins, which benefit many cardiovascular diseases due to their anti-oxidative and anti-inflammatory effects. To explore the protective effect of anthocyanin on atherosclerosis from a metabolic perspective, alterations in plasma metabolic profiling of apoE-deficient (apoE-/-) mice in response to treatment with anthocyanin extracts derived from Xinjiang wild cherry plum (Prunus divaricata Ledeb) peel was investigated through UHPLC-Q-TOF/MS. The mice were fed with a normal diet or high-fat diet supplementation with or without anthocyanin extracts (ACNE, 75, 150, 250 mg/kg body weight) for 18 weeks, corresponding to control (Con), model (Mod), and treatment group (LD, low dose; MD, medium dose; HD, high dose), respectively, along with a positive control group (posCon, treatment with Atorvastatin, 0.003 mg/kg body weight). The results showed that ACNE could significantly enhance the antioxidant capacity and lower the plasma lipid, but have no evident influence on the body weight of apoE-/- mice. A series of differential metabolites, predominantly related to lipid metabolism, were identified, including docosahexaenoic acid, palmitoyl ethanolamide, stearoylcarnitine, L-palmitoylcarnitine, indoxyl sulfate (IS), 1-palmitoyl-lysophosphatidylcholine, phenylacetylglycine (PAGly), and so on. Among these, both IS and PAGly were host-microbial metabolites. These differential metabolites were mainly enriched in the pathway of glycerophospholipid metabolism and linoleic acid metabolism. Several important enzymes related to glycerophospholipid metabolisms such as LCAT, LPCAT, GPCPD1, PLA2G1B, PPARG, LIPE, PNPLA2, AGPAT1, and ENPP2 were recognized as underlying targets for anti-atherogenic effects of ACNE. These findings suggest that ACNE derived from Xinjiang wild cherry plum exhibits protective effects against atherosclerosis via modulating glycerophospholipid metabolism.

Hu'po Anshen Decoction Accelerated Fracture-Healing in a Rat Model of Traumatic Brain Injury Through Activation of PI3K/AKT Pathway.

Hu'po Anshen decoction (HPASD) is a traditional Chinese medicine formula comprising five herbal medicines for the treatment of concussion and fracture healing, but its pharmacological mechanism is still unclear. Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS) was used to analyze the main active components of HPASD. Rats were randomly assigned to fracture group, fracture combined with traumatic brain injury (TBI) group (FBI) and FBI combined with HPASD treatment group (FBIH). Rats in the FBIH group were given oral doses of HPASD (2.4 g/kg, 4.8 g/kg and 9.6 g/kg) for 14 or 21 consecutive days. The fracture callus formation and fracture sites were determined by radiographic analysis and micron-scale computed tomography (micro-CT) analysis. Hematoxylin and eosin (H&E) staining and a three-point bending test were applied to assess histological lesions and biomechanical properties, respectively. The levels of cytokines-/protein-related to bone formation and differentiation as well as PI3K/AKT pathway-related proteins were determined by Enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription-polymerase chain reaction (qRT-PCR), or western blot assays, respectively. UPLC-Q/TOF-MS-based serum metabolomic analysis was also performed to investigate the therapeutic effects of HPASD in the treatment of FBI. UPLC/Q-TOF MS analysis showed the chemical components in HPASD, including flavonoids, amino acids, saponins, and phenylpropanoid constituents, etc. HPASD dose-dependently promoted callus formation, increased bone density, improved mechanical parameters and morphological scores, and facilitated the expressions of VEGF, PDGF, bFGF, VEGFA, CoL1A1, RUNX2, BMP2, and Aggrecan, inhibited the expression of MMP13, and activated PI3K/AKT pathway. Metabolomics analysis revealed abnormalities of malate-aspartate shuttle and glucose-alanine. HPASD accelerates fracture healing by promoting bone formation and regulating the malate-aspartate shuttle and glucose-alanine cycle, which might be associated with the activation of the PI3K/AKT pathway.

The protective effects of Mai-Luo-Ning injection against LPS-induced acute lung injury via the TLR4/NF-κB signalling pathway.

BACKGROUND: Acute lung injury (ALI) is a severe inflammatory disorder associated with high morbidity and mortality rates. Various therapeutic strategies for ALI have been proposed over the last few decades; however, the treatment options remain limited. Mai-Luo-Ning injection (MLN), a traditional Chinese medical formulation, has been extensively used for the treatment of respiratory diseases. Nevertheless, the effects of MLN on ALI remain unclear. PURPOSE: This study aimed to investigate the protective and therapeutic effects of MLN on lipopolysaccharide-induced ALI mouse models and RAW 264.7 cells, and further explore the underlying mechanism of these effects. METHODS: The therapeutic activity of MLN was evaluated using an in vivo ALI model and an in vitro model of RAW 264.7 macrophages. UHPLC-ESI-Q-TOF-MS/MS was used to investigate the chemical constituents of the MLN. The material basis and potential protective mechanism of MLN were analyzed using network pharmacology. The roles of MLN in inhibiting the Toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB) signalling pathway were investigated via western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunofluorescence staining. RESULTS: In vivo experiments demonstrated that MLN ameliorated LPS-induced histological changes in lung tissues and reduced lung wet/dry weight ratio, total protein concentration in the bronchoalveolar lavage fluid and myeloperoxidase activity. Furthermore, MLN downregulated the in vivo and in vitro expression of pro-inflammatory cytokines such as tumour necrosis factor-alpha, interleukin-6, and interleukin-1ß. Network pharmacology analysis revealed that MLN could act synergistically through multiple targets and pathways and exert a protective effect, possibly through inhibiting TLR4/ NF-κB signalling pathways. Western blotting and immunofluorescence experiments further confirmed that MLN could regulate the expression of TLR4, MyD88, phospho-IκB-α, and phospho-NF-κB p65 in the TLR4/NF-κB signalling pathway and decrease the translocation of phospho-NF-κB p65 into the nucleus. CONCLUSION: This study suggests that MLN has a potential protective effect against LPS-induced ALI, which might be associated with the inhibition of the TLR4/NF-κB signalling pathway. Therefore, MLN is worthy of further investigation as a potential candidate for the treatment of ALI in the future.

[Enrichment and Ecological Risk Assessment of Available Phosphorus in Paddy Soil of Fujian Province Over Past 40 years].

The ecological risks such as water eutrophication caused by soil phosphorus loss have attracted extensive attention, and its dynamic changes and enrichment effects are the basis for formulating reasonable control measures. In this study, based on the paddy soils of 1.8×106 hm2 in Fujian province, the dynamic changes and ecological risks of available phosphorus in paddy soils over the past 40 years were analyzedusing a soil database of 1:50000. The soil database contained 1471, 215534, and 2895 paddy soil samples in different periods, respectively. The paddy soil samples were derived from the 1982 Second National Soil Census, the 2008 Ministry of Agriculture and Rural Areas Soil Testing and Formulated Fertilization Project and the 2018 Ministry of Agriculture, and the Rural Areas Arable Land Quality Monitoring Project, respectively. The results showed that from 1982 to 2018, the content of available phosphorus in paddy soils increased by 47 mg·kg-1, and the enriched area reached 1.65×106 hm2, accounting for 91% of the total paddy soils in Fujian province. From 1982 to 2008, the available phosphorus content of paddy soils in Fujian province increased by 28 mg·kg-1, with the enriched area reaching 1.47×106 hm2, accounting for 82% of the total paddy soils in Fujian province. From 2008 to 2018, the available phosphorus content of paddy soils in Fujian province increased by 19 mg·kg-1, with the enriched area reaching 1.22×106 hm2, accounting for 69% of the total paddy soils in Fujian province. Further ecological risk assessment showed that from 2008 to 2018, the area of paddy soil with ecological phosphorus enrichment risk in the province gradually increased, mainly distributed in percogenic paddy soils and hydromorphic paddy soils with a slope of less than 2°. In the future, effective phosphorus fertilizer management measures should be formulated for different types of paddy soil to prevent the occurrence of environmental problems such as water eutrophication.

Abdominopelvic Lymphatic Drainage Area Irradiation for Consolidative Radiotherapy of Advanced Ovarian Carcinoma: Analysis of Clinical Application Efficacy and Dosimetric Verification.

Background: The aim of the study was to evaluate the efficacy of abdominopelvic lymphatic drainage area irradiation (APLN), instead of whole abdominal radiotherapy (WART), in the consolidative radiotherapy of advanced ovarian carcinoma patients. Methods: We conducted a retrospective analysis collecting 99 patients with locally advanced ovarian cancer treated by APLN with 45 - 50 Gy/25- 28 fractions/5-7#, instead of WART. We evaluated the clinical outcome of APLN. Five patients were selected for dosimetric verifications verses WART (30 Gy/20 fractions). The normal tissue complication probability (NTCP) was calculated for the two treatment methods. Results: The mean follow-up time was 64.10 months (5.5 - 113.2 months), after APLN consolidative radiotherapy, 1-, 3-, and 5-year overall survival (OS) was 87.9%, 81.3%, and 61.5%, median disease-free survival (DFS) was 40.8 months, 5-year local recurrence free survival (LRFS) was 75.9%, and 5-year distant metastasis free survival (DMFS) was 49.2%. One patient died due to intestinal perforation. Local recurrence in the area between WART and APLN was rare (3/99 patients). The number of surgical procedures < 2 was an independent risk factor for LRFS (P = 0.023). Dosimetric comparison showed that comparing with WART, APLN significantly reduced the organ at risk (OAR) dose: 25.37 ± 3.63 Gy (25%) for liver, 8.77 ± 5.03 Gy (25%) for kidney, 8.14 ± 1.51 Gy (25%) for small intestine, etc. NTCP was reduced by 0.04-1.04% for liver, kidney, and small intestine. Conclusion: For consolidative radiotherapy in locally advanced ovarian cancer, APLN (intensity-modulated radiotherapy 45 - 50 Gy/25 - 28 fractions) could be an alternative to WART, resulting in excellent LRFS and DFS, with acceptable toxicities, comparing with previous literature reports. Dosimetric analysis also showed the benefits of APLN in NTCP.

[Mechanism of Qingwei Powder in treatment of periodontitis based on UPLC-Q-TOF-MS, GC-MS, network pharmacology and molecular docking].

The present study explored the mechanism of Qingwei Powder(QP) in the treatment of periodontitis based on chromatography-mass spectrometry and network pharmacology-molecular docking techniques. UPLC-Q-TOF-MS and GC-MS were used to identify the chemical constituents of QP. The active components and targets were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and their targets were predicted using SwissTargetPrediction. Targets related to periodontitis were obtained from GeneCards, OMIM, and DisGeNET. Venn diagram was constructed using Venny 2.1 to obtain the intersection targets. Cytoscape 3.7.2 was used to construct the "chemical component-target-disease" network. The targets were analyzed for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by clusterProfiler R, and the "chemical component-target-pathway" network was constructed. The binding activity of the active components to the target proteins was verified by molecular docking. A total of 189 chemical components were obtained by UPLC-Q-TOF-MS and GC-MS, including 39 active components with 180 potential targets related to periodontitis. Target enrichment analysis of the active components yielded 92 KEGG pathways. Twenty KEGG pathways, 34 active components, and 99 targets were involved in the "chemical component-target-pathway" network. Molecular docking verified a good binding ability of the key targets to the key compounds. This study preliminarily indicates that QP is effective in treating periodontitis through multiple components, multiple targets, and multiple pathways, which reflects the complex system of Chinese medicine. This study provides the theoretical foundation for the subsequent research on the material basis and key quality attributes of QP.

Pueraria lobata starch regulates gut microbiota and alleviates high-fat high-cholesterol diet induced non-alcoholic fatty liver disease in mice.

The dried roots of Pueraria lobata (Willd.) Ohwi as an edible medicinal herb are enriched with starch. However, the structure, physiology, and biological bioactivity of P. lobata starch (PLS) has not yet been fully investigated. This study showed that PLS consisted of mixed population of granules with polyhedral or spherical surface. The apparent content of resistant starch was 23.14%, and the molecular weight was 1.93 × 107 Da. PLS showed a branching degree and an average polymerization rate of 2.06% and 20.74%, respectively, with fairly high proportion of B1 short chains. The solubility and swelling power of PLS were 38.51% and 28.10 g/g, respectively, showing high hot stability of the viscosity. In vitro fermentation of PLS resulted in specifically altered composition of gut microbiota and increased production of SCFAs, showing a potential prebiotic effect. Moreover, PLS remarkably alleviated inflammation, hepatic steatosis and dyslipidemia in mice with high-fat high-cholesterol diet induced non-alcoholic fatty liver disease (NAFLD). The protective effect of PLS was associated with amelioration of NAFLD-associated gut dysbiosis through specifically increasing the abundance of Lactobacillus, Bifidobacterium and Turicibacter, and decreasing Desulfovibrio. The results would support the use of PLS as a functional prebiotic for protecting against NAFLD.

Semiconducting Polymer Nanoparticles with Intramolecular Motion-Induced Photothermy for Tumor Phototheranostics and Tooth Root Canal Therapy.

Much effort is devoted to develop agents with superior photoacoustic/photothermal properties for improved disease diagnosis and treatment. Herein, a new fused two isoindigo (DIID)-based semiconducting conjugated polymer (named PBDT-DIID) is rationally designed and synthesized with a strong near-infrared absorption band ranging from 700 to 1000 nm. Water-dispersing nanoparticles (NPs) of PBDT-DIID are prepared with good biocompatibility and a rather high photothermal conversion efficiency (70.6%), as the active excited-state intramolecular twist around the central double bonds in DIID permits most of the absorbed excitation energy flow to heat deactivation pathway through internal conversion. The photoacoustic signal can be further magnified by incorporation of polylactide (PLA) in the NP core to confine the generated heat of PBDT-DIID within NPs. The resultant doped NPs show excellent performance in photoacoustic imaging-guided photothermal therapy in an orthotopic 4T1 breast tumor-bearing mouse model. It is also found that the photothermal effect of the PBDT-DIID NPs is safe and quite efficacious to highly improve the root canal treatment outcome by heating the 1% NaClO solution inside the root canal upon 808 nm laser irradiation in a human extracted tooth root canal infection model.

The Role of Vitamin D in Gastrointestinal Diseases: Inflammation, Gastric Cancer, and Colorectal Cancer.

Vitamin D as a prohormone is converted into the active form in vivo and binds to vitamin D receptors, exercising a wide range of biological functions. Recent studies strongly support that vitamin D supplementation is associated with reduced cancer risk and a good prognosis. Gastrointestinal cancer is the leading cause of cancer-related deaths worldwide. The key role of vitamin D in the development of gastrointestinal cancer has been observed. Moreover, Vitamin D can also affect innate immunity and perform anti-inflammation and anti-infection actions. Given the intimate relationship between cancer and inflammation, we herein summarize epidemiological and preclinical studies of vitamin D and the underlying mechanism of its action in inflammation, gastric and colorectal cancer by our group and other researchers. A beneficial effect of vitamin D in cancer and inflammatory disease has been supported by different studies. More controlled and larger clinical trials are needed before a reliable conclusion and realization of vitamin D supplementation in the adjunct treatment of gastrointestinal inflammation and cancer.