Abstract Alhagi honey (AH) is produced in arid and hot areas of Central Asia, and its polysaccharides (AP) are widely known for their activity in the treatment of intestinal diseases such as diarrhea. However, the therapeutic potential and mechanism of AP in ulcerative colitis (UC) remain unclear. Here, AH polysaccharide‐2 (AP2), a polysaccharide with the highest content in AP, was isolated and evaluated for its effects on dextran sulfate sodium (DSS)‐induced UC in mice. AP2 was found to alleviate UC symptoms and regulate gut microbiota dysbiosis by decreasing Helicobacter levels and increasing Lactobacillus levels. Analysis of PICRUSt2 predicted that AP2 may regulate carbohydrate and amino acid metabolism, and metabolomic analysis confirmed that AP2 promotes the metabolism of tryptophan to produce kynurenic acid (kyna). Moreover, kyna acted as an aryl hydrocarbon receptor (AhR) ligand, which activated AhR to increase the expression of the tight junction proteins claudin‐1 and occludin. Interestingly, AP2 showed similar effects in protecting the intestinal barrier and alleviating colitis as the AhR agonist 6‐formylindolo[3,2‐ b ]carbazole, and the AhR antagonist CH223191 partially blocked the therapeutic effect of AP2 in UC mice, indicating that the anti‐UC effect of AP2 was AhR dependent. These findings demonstrate that AP2 alleviates UC by regulating the gut microbiota and promoting tryptophan metabolism to generate kyna‐activated AhR. The insights gained from this study could help in the future development of AP2 as a drug candidate or functional food for the treatment of UC.
Objective
To investigate the clinical efficacy of three-dimensional visualization technique (3DVT) combined with enhanced recovery after surgery (ERAS) in the treatment of hepatolithiasis.
Methods
The retrospective cohort study was conducted. The clinicopathological data of 64 patients with hepatolithiasis who were admitted to Zhujiang Hospital of Southern Medical University from November 2015 to August 2018 were collected. There were 17 males and 47 females, aged from 30 to 82 years, with a median age of 55 years. Of the 64 patients, 23 who completed preoperative assessment and planning using 3DVT, and furthermore received ERAS for perioperative management were divided into 3DVT + ERAS group, and 41 who received preoperative assessment merely under the guidance of 3DVT, combined with conventional perioperative management were divided into 3DVT + conventional group. Observation indicators: (1) preoperative CT and 3DVT assessment; (2) perioperative conditions; (3) follow-up. The follow-up was conducted by outpatient service, e-mail or telephone interview to detect the postoperative recurrence of hepatolithiasis up to March 2019. The measurement data with normal distribution were expressed as Mean±SD, and the t test was used for comparison between groups. The measurement data with skewed distribution were expressed as M (P25, P75), and the Mann-Whitney U test was used for comparison between groups. The count data were expressed as absolute numbers or percentages, and the comparison between groups was performed using the chi-square test or Fisher exact probability.
Results
(1) Preoperative CT and 3DVT assessment: 23 patients in the 3DVT + ERAS group underwent preoperative CT examination and 3DVT assessment, the consistency between CT results and intraoperative findings was 91.3%(21/23), and the consistency between 3DVT results and intraoperative findings was 95.7%(22/23). Fourty-one patients in the 3DVT + conventional group underwent preoperative CT examination and 3DVT assessment, the consistency between CT results and intraoperative findings was 90.2%(37/41), and the consistency between 3DVT results and intraoperative findings was 95.1%(39/41). (2) Perioperative conditions: the volume of intraoperative blood loss, duration of postoperative hospital stay, postoperative total bilirubin, postoperative direct bilirubin, postoperative albumin, postoperative alanine aminotransferase, postoperative aspartate aminotransferase and postoperative hemoglobin were 50 mL (10 mL, 100 mL), 8 days (7 days, 9 days), 12 μmol/L (9 μmol/L, 16 μmol/L), 6 μmol/L (4 μmol/L, 8 μmol/L), (37±4)g/L, 44 U/L (18 U/L, 85 U/L), 32 U/L (20 U/L, 65 U/L), (117±18)g/L in the 3DVT + ERAS group, and 100 mL (50 mL, 300 mL), 13 days (10 days, 16 days), 17 μmol/L (12 μmol/L, 33 μmol/L), 11 μmol/L (7 μmol/L, 21 μmol/L), (29±6)g/L, 78 U/L (43 U/L, 122 U/L), 121 U/L (72 U/L, 176 U/L), (106±13)g/L in the 3DVT + conventional group, respectively; there were significant differences between two groups (Z=-3.084, -4.827, -2.953, -3.632, t=5.261, Z=-2.960, -4.625, t=2.773, P<0.05). Two patients had pulmonary infection and 2 had pleural effusion in the 3DVT + ERAS group, and all the 4 patients were cured after treatment. One case of biliary fistula, 4 cases of pulmonary infection and 5 cases of pleural effusion occurred in the 3DVT + conventional group, and these patients were cured by adequate abdominal drainage, antibiotic therapy and thoracocentesis, respectively. There was no perioperative death in either group. (3) Follow-up: 64 patients were followed up for 6-36 months, with a median time of 23 months. During the follow-up, no recurrent hepatolithiasis in the 3DVT + ERAS group, and 1 case of recurrent hepatolithiasis was confirmed by ultrasound in the 3DVT + conventional group. No cholangiocarcinoma occurred in either group.
Conclusion
The combination of 3DVT and ERAS is effective, safe and feasible in the management of hepatolithiasis, which can accelerate the postoperative recovery of liver function, thus enhancing perioperative recovery and improving the prognosis of patients simultaneously.
Key words:
Hepatolithiasis; Three-dimensional visualization; Enhanced recovery after surgery; Efficacy; Diagnosis; Management
Although the prognostic value of nodal metastases in differentiated thyroid cancer remains controversial, it is of interest to evaluate and understand the different characteristics of predictive outcomes. A multicenter retrospective study was conducted in 215 untreated patients with differentiated thyroid cancer from July 1997 to July 2015 in 4 medical centers of Guangdong Province. A total of 107 patients with nodal metastases (group A) were compared to 108 patients without metastases (group B). The 5-year disease-free survival (DFS), overall survival (OS), and postoperative complications in both groups were calculated. Variables predictive of DFS and OS were evaluated in group A. The group A had lower 5-year DFS (69.16%, 11 months) and shorter median time of recurrence than those in group B (87.96%, 8.5 months, respectively, P < 0.001). The incidence of temporary hypoparathyroidism in group A is lower; whereas higher incidence of temporary unilateral vocal cord palsy, permanent hypoparathyroidism, permanent unilateral vocal cord palsy, and bilateral vocal cord palsy in group A were observed. Both univariate and multivariate analyses in group A revealed that age, pathological tumor node metastasis (pTNM) stage, and histology were related to DFS (P < 0.05); while pTNM stage and histology were related to OS only in univariate analyses. Positive nodal metastases have significant prognostic value in patients with differentiated thyroid cancer in Guangdong, China and primarily reduce DFS. Moreover, patients with positive nodal metastases who are >45 years and have higher pTNM stage or follicular histology tend to have poor prognosis. Selective lymph node dissection with appropriate postoperative treatment and frequent follow-up should be accorded to these vulnerable groups of patients.
We report wide-field polygon-scanning functional OR-PAM that for the first time achieves 1-MHz A-line rate of oxygen saturation in vivo. We address two technical challenges. The first is a 1-MHz dual-wavelength pulsed laser that has sufficient pulse energy and ultrafast wavelength switching. The second is a polygon-scanning imaging probe that has a fast scanning speed, a large field of view, and great sensitivity. The OR-PAM system offers a B-scan rate of 477.5 Hz in a 12-mm range and a volumetric imaging rate of ∼1 Hz over a 12 × 5 mm
Currently the extent of lymph node dissection (LND) for papillary thyroid microcarcinoma (PTMC) remains controversial. The present study aims to investigate the clinicopathologic predictors of lymph node metastasis (LNM) and prognosis in PTMC patients from Guangdong to enable appropriate treatment and follow-up.Data including demographics, tumor size, multifocality, extrathyroidal extension (ETE) and concomitant thyroiditis were collected from 374 untreated PTMC patients from Guangdong, China. Univariate and multivariate analyses were performed to identify clinicopathologic predictors of LNM and prognostic indicators in PTMC patients with LNM.During the follow-up period of 120 months, recurrence was significantly higher in patients with LNM than in patients without LNM (P<0.05). Age <45 years, larger tumor (>5 mm) and multifocality were predictors of LNM; age <45 years, larger tumor size and absence of concomitant thyroiditis were associated with central LNM (CLNM); male sex, ETE and multifocality were correlated with lateral LNM (LLNM) (P<0.05). There was no difference in recurrence between patients with CLNM and LLNM (P>0.05). LNM in PTMC primarily influenced disease-free survival. Age >45 years and male sex were risk factors of recurrence in PTMC patients with LNM. Male patients with CLNM and older patients with LLNM exhibited worse prognosis (P<0.05).PTMC easily metastasizes to cervical lymph nodes, which significantly influences prognosis. Prophylactic LND is recommended in PTMC patients from Guangdong, China, who have a high risk of CLNM and/or LLNM. More aggressive postoperative treatment and more frequent follow-up could be considered for older and/or male PTMC patients with LNM.
80% of advanced cancer patients suffer from cachexia, but there are no FDA-approved drugs. Therefore, it is imperative to discover potential drugs. Objective: This study aims at exploring the effect and targets of Aloin A against cancer cachexia (CC)-induced muscle atrophy. Methods: Network pharmacology, molecular docking, molecular dynamics (MD) and animal model of CC-induced muscle atrophy with a series of behavior tests, muscle quality, HE staining and RT-PCR were performed to investigate the anticachectic effects and targets of Aloin A and its molecular mechanism. Results: Based on network pharmacology, 51 potential targets of Aloin A on CC-induced muscle atrophy were found, and then 10 hub genes were predicted by the PPI network. Next, KEGG and GO enrichment analysis showed that the anticachectic effect of Aloin A is associated with PI3K-AKT, MAPK, TNF, TLR, etc., pathways, and biological processes like inflammation, apoptosis and cell proliferation. Molecular docking and MD results showed good binding ability between the Aloin A and key targets. Moreover, experiments in vivo demonstrated that Aloin A effectively rescued muscle function and wasting by improving muscle quality, mean CSA, and distribution of muscle fibers by regulating HSP90AA1/AKT signaling in tumor-bearing mice. Conclusion: This study offers new insights for researchers to understand the effect and mechanism of Aloin A against CC using network pharmacology, molecular docking, MD and experimental validation, and Aloin A retards CC-induced muscle wasting through multiple targets and pathways, including HSP90AA1/AKT signaling, which provides evidence for Aloin A as a potential therapy for cancer cachexia in clinic.
To date, plant medicine research has focused mainly on the chemical compositions of plant extracts and their medicinal effects. However, the therapeutic or toxic effects of nanoparticles in plant extracts remain unclear. In this study, large numbers of spherical nanoparticles were discovered in some plant extracts. Nanoparticles in Turkish galls extracts were used as an example to examine their pH responsiveness, free radical scavenging, and antibacterial capabilities. By utilizing the underlying formation mechanism of these nanoparticles, a general platform to produce spherical nanoparticles via direct self-assembly of Turkish gall extracts and various functional proteins was developed. The results showed that the nanoparticles retained both the antibacterial ability and intracellular carrier ability of the original protein or catechol. This work introduces a new member of the plant-derived edible nanoparticle (PDEN) family, establishes a simple and versatile platform for mass production nanoparticles, and provides new insight into the formation mechanism of nanoparticles during plant extraction.
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