A tumor-targetable NIR probe with photoaffinity crosslinking characteristics for enhanced imaging-guided cancer phototherapy.

Spatiotemporally manipulating the in situ immobilization of theranostic agents within cancer cells to improve their bioavailability is highly significant yet challenging in tumor diagnosis and treatment. Herein, as a proof-of concept, we for the first time report a tumor-targetable near-infrared (NIR) probe DACF with photoaffinity crosslinking characteristics for enhanced tumor imaging and therapeutic applications. This probe possesses great tumor-targeting capability, intensive NIR/photoacoustic (PA) signals, and a predominant photothermal effect, allowing for sensitive imaging and effective photothermal therapy (PTT) of tumors. Most notably, upon 405 nm laser illumination, DACF could be covalently immobilized within tumor cells through a photocrosslinking reaction between photolabile diazirine groups and surrounding biomolecules resulting in enhanced tumor accumulation and prolonged retention simultaneously, which significantly facilitates the imaging and PTT efficacy of tumor in vivo. We therefore believe that our current approach would provide a new insight for achieving precise cancer theranostics.

An ethnobotanical study on medicinal plants of Shexian Dryland Stone Terraced System in northern China.

BACKGROUND: Shexian Dryland Stone Terraced System (SDSTS) in the Taihang Mountains was formally recognized as Globally Important Agricultural Heritage Systems (GIAHS) by Food and Agriculture Organization on May 20, 2022. People there have been relying on the terraced fields for centuries, using various plants, including medicinal plants. However, little information was reported about the flora in SDSTS, nor medicinal plants. Thus, the present study aims to identify and document medicinal plants traditionally used by the local people living around the SDSTS and associated ethnobotanical knowledge. METHODS: We conducted investigations in Shexian County, Hebei Province, North China, where SDSTS is distributed. Then, Wangjinzhuang, a community located in the core zone of SDSTS, was chosen as the case site. We selected the informants through purposive and snowball sampling. The data were collected through semi-structured interviews, participant observation, and key informant interviews. The medicinal plants traditionally used by the local people were documented and analyzed. We examined and confirmed the botanical identification based on voucher specimens and by cross-checking the descriptions with the series of books, scientific papers on medicinal plants, and the plant databases. RESULTS: The local people have rich traditional knowledge to collect and use medicinal plants in SDSTS. Records of 123 medicinal plant species belonging to 51 families were obtained from SDSTS. Asteraceae was represented by 16 species, followed by Fabaceae, Lamiaceae and Ranunculaceae. (They all have 8 species.) The majority of the reported plant species were commonly processed into decoctions. And 180 diseases affecting humans were reported to be treated with traditional medicinal plants from SDSTS. CONCLUSION: It is the first ethnobotanical study on medicinal plants in China-Nationally Important Agricultural Heritage Systems, and in globally important agricultural heritage systems as well. Medicinal plants are crucial for people living in Shexian County. It is necessary to recognize and respect traditional knowledge peculiar to the mountainous region of northern China, especially for those involved in the human-nature interaction and the role of knowledge in agrobiodiversity conservation and rural development that local residents have persisted for centuries.

Capecitabine versus 5-fluorouracil in neoadjuvant chemoradiotherapy of locally advanced rectal cancer: A meta-analysis.

BACKGROUND: The differences in efficacy between capecitabine and 5-fuorouracil (5-FU) in neoadjuvant chemoradiotherapy (CRT) of locally advanced rectal cancer (LARC) are not well recognized. We performed this meta-analysis to analyze the effect of capecitabine and 5-FU on neoadjuvant CRT to more accurately understand the differences between the 2 drugs. METHODS: MEDLINE, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database were performed to identify all published studies investigating the efficacy of capecitabine in neoadjuvant CRT of LARC versus 5-FU before August, 2017. Primary endpoint was the odds ratio (OR) for improving pathological complete response (pCR) rate of patients with LARC. Secondary endpoints were the ORs of efficiency for downstaging tumor and increasing R0 resection in patients with LARC. Safety analyses were also performed. The OR was the principal measurement of effect, which was calculated as capecitabine group versus 5-FU group, and was presented as a point estimate with 95% confidence intervals (CIs). All calculations and statistical tests were performed using RevMan 5.3 software. RESULTS: In all, 2916 patients with LARC enrolled in the 10 studies were divided into capecitabine group (n = 1451) and 5-FU group (n = 1465). The meta-analysis showed that capecitabine improved pCR (OR 1.34, 95% CI 1.10-1.63), and R0 resection rate (OR 1.92, 95% CI 1.10-3.36). There were no statistically significant differences either in overall downstaging rate (OR 1.31, 95% CI 0.79-2.16) or in the tumor downstaging rate (OR 1.24, 95% CI 0.79-1.92), but there was a significant difference of the nodal downstaging rate between the 2 groups (OR 1.68, 95% CI 1.11-2.54). There was no statistically significant difference in sphincter preservation rate between the 2 groups (OR 1.36, 95% CI 0.96-1.92). No obvious safety concerns about mortality and complications were raised in these studies. There were no statistically significant differences in 3-year disease-free-survival (OR 1.29, 95% CI 0.75-2.20), and in grade 3 to 4 acute toxicity during CRT (OR 0.63, 95% CI 0.31-1.30). CONCLUSIONS: Compared with 5-FU-based neoadjuvant CRT, capecitabine-based neoadjuvant CRT can safely improve pCR, nodal down-staging, ad R0 resection of patients with LARC.

Cervical cancer treated with reduced-volume intensity-modulated radiation therapy base on Sedlis criteria (NCCN VS RTOG).

OBJECTIVE: This study aimed to evaluate the clinical efficacy of different target volumes in pelvic radiotherapy in postoperative treatment of cervical cancer based on the Sedlis criteria. METHODS: Patients who admitted to our department for post-operative radiotherapy of cervical cancer from December 2001 to December 2011 and met the Sedlis criteria were retrospectively analysed. The incidences of acute and late radiation injuries, and overall, disease-free and tumour-specific survival with reduced-volume pelvic and whole-pelvis radiotherapy were evaluated and compared. RESULTS: A total of 371 patients were included in the study, including 239 receiving whole-pelvis radiotherapy and 132 receiving reduced-volume pelvic radiotherapy. The volume of contours for mean PTV volumes, bilateral femoral heads and small intestine volumes in reduced-volume pelvic radiotherapy were lower than whole-pelvis radiotherapy; the results were similar to the V10, V20, V30, V40 and V45 for pelvic bone marrow and small intestine dose volume (both p < 0.05). The acute radiation injury observed in the two groups was mainly haematologic toxicity and upper and lower gastrointestinal symptoms. The incidences of acute radiation injury, and late radiation injury of gastrointestinal and urinary tracts were both significantly lower with reduced-volume pelvic radiotherapy than with whole-pelvis radiotherapy (both p < 0.05). Moreover, there was no significant difference in the incidence of lower extremity oedema, or 2-year or 5-year overall, disease-free or tumour-specific survival between groups (all p > 0.05). CONCLUSION: Reduced-volume pelvic radiotherapy could relieve acute and late radiation injuries, especially myelosuppression, and did not affect long-term survival. Advanced in knowledge: Our study shows that reduced-volume base on National Comprehensive Cancer Network 2016 is more fit for cervical cancer than others.

Protective Effects of Dietary Supplementation with a Combination of Nutrients in a Transgenic Mouse Model of Alzheimer's Disease.

OBJECTIVE: This study investigated the effects of intervention with a combination of nutrients in the amyloid precursor protein-presenilin (APP-PSN) C57BL/6J double transgenic mouse model of Alzheimer's disease (AD). METHODS: A total of 72 2-month-old APP-PSN mice were randomly assigned to three groups. The model group (MG) was fed regular, unsupplemented chow, while the low- and high-dose treatment groups (LG and HG, respectively) were given a combination of nutrients that included phosphatidylserine, blueberry extracts, docosahexaenoic acid, and eicosapentaenoic acid as part of their diet. An additional 24 wild-type littermates that were fed unsupplemented chow served as the negative control group (NG). After 3 and 7 months of treatment, the cognitive performance was assessed with the Morris water maze and the shuttle box escape/avoidance task, and the biochemical parameters and oxidative stress were evaluated in both the blood and brain. RESULTS: An improvement in antioxidant capacity was observed in the treatment groups relative to the MG at 3 months, while superior behavioral test results were observed in the mice of the HG and NG groups. In the MG, pycnosis was detected in neuronal nuclei, and a loss of neurons was observed in the cerebral cortex and the hippocampus. At 7 months, the ß-amyloid1-42 peptide accumulation was significantly elevated in the MG but was markedly lower in the mice fed the nutrient combination. The antioxidant capacity and behavioral test scores were also higher in these mice. CONCLUSIONS: Early intervention with a combination of nutrients should be considered as a strategy for preventing cognitive decline and other symptoms associated with AD.

Effectiveness of 5-flurouracil-based neoadjuvant chemotherapy in locally-advanced gastric/gastroesophageal cancer: a meta-analysis.

AIM: To investigate the effectiveness of 5-flurouracil-based neoadjuvant chemotherapy (NAC) for gastroesophageal and gastric cancer by meta-analysis. METHODS: MEDLINE and manual searches were performed to identify all published randomized controlled trials (RCTs) investigating the efficacy of the flurouracil-based NAC for gastroesophageal and gastric cancer, and RCTs of NAC for advanced gastroesophageal and gastric cancer vs no therapy before surgery. Studies that included patients with metastases at enrollment were excluded. Primary endpoint was the odds ratio (OR) for improving overall survival rate of patients with gastroesophageal and gastric cancer. Secondary endpoints were the OR of efficiency for down-staging tumor and increasing R0 resection in patients with gastroesophageal and gastric cancer. Safety analyses were also performed. The OR was the principal measurement of effect, which was calculated as the treatment group (NAC plus surgery) vs control group (surgery alone) and was presented as a point estimate with 95% confidence intervals (CI). All calculations and statistical tests were performed using RevMan 5.1 software. RESULTS: Seven RCTs were included for the analysis. A total of 1249 patients with advanced gastroesophageal and gastric cancer enrolled in the seven trials were divided into treatment group (n = 620) and control group (n = 629). The quality scores of the RCTs were assessed according to the method of Jadad. The RCT quality scores ranged from 2 to 7 (5-point scale), with a mean of 3.75. The median follow-up time in these studies was over 3 years. The meta-analysis showed that NAC improved the overall survival rate (OR 1.40, 95%CI 1.11-1.76; P = 0.005), which was statistically significant. The 3-year progression-free survival rate was significantly higher in treatment group than in control group (37.7% vs 27.3%) (OR 1.62, 95%CI 1.21-2.15; P = 0.001). The tumor down-stage rate was higher in treatment group than in control group (55.76% vs 41.38%) (OR 1.77, 95%CI 1.27-2.49; P = 0.0009) and the R0 resection rate of the gastroesophageal and gastric cancer was higher in treatment group than in control group (75.11% vs 68.56%) (OR 1.38, 95%CI 1.03-1.85; P = 0.03), with significant differences. No obvious safety concerns about mortality and complications were raised in these trials. There were no statistically significant differences in perioperative mortality (5.08% vs 4.86%) (OR 1.05, 95%CI 0.57-1.94; P = 0.87 fixed-effect model) and in the complication rate between the two groups (13.25% vs 9.66%) (OR 1.40, 95%CI 0.91-2.14; P = 0.12 fixed-effect model). Trials showed that patients from Western countries favored NAC compared with those from Asian countries (OR 1.40, 95%CI 1.07-1.83). Monotherapy was inferior to multiple chemotherapy (OR 1.40, 95%CI 1.07-1.83). Intravenous administration of NAC was more advantageous than oral route (OR 1.41, 95%CI 1.09-1.81). CONCLUSION: Flurouracil-based NAC can safely improve overall survival rate of patients with gastroesophageal/gastric cancer. Additionally, NAC can down the tumor stage and improve R0 resection.