OBJECTIVE Angiogenesis therapy has attracted interest as a potential treatment for hepatocellular carcinoma (HCC). In this study, we investigated the anti-proliferative activities and anti-angiogenesis effects of saikosaponins (SS)-b on hepatocellular carcinoma (HCC) and its regulation on VEGF/ERK/HIF-1α signal pathway. METHODS H22 hepatoma-bearing mice model and HepG-2 cells were used to study the anti-tumor and anti-angiogenesis effects of SS-b in vivo and in vitro. Pathological change of tumor tissue was observed by HE staining, the microvascular changes were detected by immunohistochemical method. The effects of SS-b on angiogenesis were examined by using the chick embryo chorioallantoic membrane (CAM) model. The effects of SS- b on proliferation, migration and invasion were investigated by MTT assay, scratch wound healing assay and transwell assay inhuman umbilical vein endothelial cell (HUVEC) and HepG2 cells in vitro. Vascular endothelial growth factor (VEGF), matrix metalloproteinase-2/9(MMP-2/9), hypoxia-inducible factor-1α (HIF-1α) expression and the phosphorylation of extracellular regulated kinase(ERK) were analyzed using RT-PCR and Western-blot. RESULTS SS-b effectively inhibited the tumor growth of H22 mice in vivo. The inhibitory rate of tumor was 49.1%, 50.7%, 66.1% in SS-b 5, 10 and 20 mg·kg-1 group respectively. HE staining results showed that SS-b induced tumor necrosis and nuclear dissolution in H22 mice. Moreover, SS-b also reduced the number of microvessels of tumor tissue in H22 mice significantly and suppressed the angiogenesis of CAM induced by b-FGF. SS-b had an obvious inhibitory effect on cell proliferation, migration and invasion of HUVEC cells and HepG-2 cells. These effects were associated with down-regulation of the expression of MMP2/9 and suppression of VEGF/ERK/HIF-1α signaling in H22 mice and Hep-G2 cells. CONCLUSION Our findings showed that SS-b exerts anti-tumor effects by inhibit?ing tumor angiogenesis via regulating VEGF/ERK/HIF-1α signal pathway in vivo and in vitro.

Female ; Heart Atria ; diagnostic imaging ; surgery ; Heart Neoplasms ; diagnostic imaging ; surgery ; Humans ; Leiomyomatosis ; diagnostic imaging ; surgery ; Magnetic Resonance Imaging ; Middle Aged ; Ultrasonography

The effective exploitation of natural products is of great significance. Herein the essential oil from Herba Artimisiae Sieversianae in growth period and flower/ fruit bearing period was extracted by ethanol extraction method. The optimal extraction condition was determined by orthogonal experiment, including extracting 3 times, soaking for 90 min, and the ratios of liquid to solid for Herba Artimisiae Sieversianae in growth period and flower/ fruit bearing period were 10 mL : 1 g and 8 mL : 1 g, respectively. The main components of the products were confirmed by FT-IR and GC-MS, which were cineole, camphor, d-borneol, caryophyllene, cadina-1, 4-diene, calamenene, ethyl palmitate, etc. in herba artimisiae sieversianae in growth period, and camphor, caryophyllene, borneol, neryl formate, etc. in Herba Artimisiae Sieversianae in flower/ fruit bearing period. The radical scavenging activity of the products was determined. The results showed that the IC50 values of the essential oil from Herba Artimisiae Sieversianae in growth period and flower/fruit bearing period for 0. 05 mmol/ L DPPH solution were 0. 40 mg / mL and 1. 66 mg / mL, respectively. The essential oil extracted by ethanol from Herba Artimisiae Sieversianae was confirmed to possess good antioxidant activity.

Objective: To compare the clinicopathological characteristics and the prognosis of gastric adenocarcinoma patients with and without neuroendocrine differentiation (NED) after radical gastrectomy plus D2 lymph node dissection. Methods: A retrospective cohort study was performed. The inclusion criteria were as follows: (1) patients who underwent radical resection of gastric cancer plus D2 lymph node dissection and were confirmed as gastric adenocarcinoma by postoperative pathology and received immunohistochemical examination of neuroendocrine markers Syn and/or CgA; (2) patients aged 20 to 75 years with normal organ function; (3) patients who did not receive neoadjuvant chemotherapy or radiotherapy before operation; (4) patients with postoperative pathological stage I to III according to the 8th edition of tumor staging system of American Joint Committee on Cancer (AJCC); and (5) patients who completed adjuvant chemotherapy according to the postoperative pathological stage. Those who had other malignant tumors in the past 5 years and who could not be followed up according to the required rules were excluded. According to the above criteria, the clinicopathological characteristics of gastric cancer patients who underwent radical resection plus D2 lymph node dissection in Zhongshan Hospital of Fudan University from January 2010 to June 2017 were collected and compared. All patients were followed up till June 2020. The disease-free survival (DFS) and overall survival (OS) between the patients with and without NED were compared, and the effect of NED on the prognosis was corrected by Cox proportional hazards model. The propensity score matching method was used for sensitivity analysis. Results: A total of 539 patients were enrolled in this study, including 35 with NED and 504 without NED. Compared with the patients without NED, the patients with NED were older [(65.0±7.5) years vs. (54.5±11.3) years, t=-7.681, P<0.001], had higher proportion of undergoing proximal gastrectomy [22.9% (8/35) vs. 7.6% (36/504), χ(2)=10.335, P=0.006], higher proportion of intestinal-type based on Lauren classification [77.1% (27/35) vs. 42.5% (214/504), χ(2)=14.553, P<0.001], and higher proportion of pathologic stage III [65.7% (23/35) vs. 27.6% (139/504), χ(2)=25.653, P<0.001]. The 3-year DFS of patients with NED and those without NED was 48.9% (95% CI: 33.8%-70.8%) and 37.4% (95% CI: 32.9%-42.5%) respectively, and no significant difference was found (P=0.44). The 3-year OS was 56.1% (95% CI: 39.9%-79.1%) and 64.3% (95% CI: 59.3%-69.7%) respectively, and no significant difference was found as well (P=0.32). Univariate and multivariate analyses showed that NED was not an independent risk factor for DFS and OS (all P>0.05). Sensitivity analysis showed that there was no significant difference in DFS and OS between the two groups after propensity score matching. Conclusion: Compared with patients without NED, patients with NED were older at onset, had a higher proportion of proximal gastrectomy, intestinal-type, and later diagnostic stage, but the survival prognosis had no significant difference with that of patients without NED.
Adult ; Aged ; Gastrectomy ; Humans ; Lymph Node Excision ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Young Adult

A retrospective analysis of a case of death from sudden convulsions caused by oral high-dose diquat was conducted, and the mechanism and treatment of central damage caused by diquat were investigated to lay the foundation for increasing the success rate of treatment of high-dose diquat poisoning. At the same time, at the same time, our clinical treatment experience has also been accumulated.
Diquat ; Humans ; Poisoning ; Retrospective Studies ; Seizures

The enzymatic browning is one of the main reasons for affecting the quality of medicinal flowers. In the process of chrysanthemum harvesting and processing, improper treatment will lead to the browning and severely impact the appearance and quality of chrysanthemum. Peroxidase enzyme is one of the oxidoreductases that cause enzymatic browning of fresh chrysanthemum. The enzymatic characteristics of peroxidase (POD) in chrysanthemum were studied in this paper. In this experiment, the effects of different reaction substrates and their concentrations, PH value of buffer and reaction temperatures on the activity of POD enzyme were investigated. The results showed that the optimal substrate of POD was guaiacol, and the optimal concentration of POD was 50 mmol·L⁻¹. The optimal pH value and reaction temperature were 4.4 and 30-35 °C, respectively. Michaelis-Menten equation was obtained to express the kinetics of enzyme-catalyzed reaction of POD, Km=0.193 mol·L⁻¹, Vmax=0.329 D·min⁻¹. In addition, the results of POD enzyme thermal stability test showed that the POD enzyme activity was inhibited when being treated at 80 °C for 4 min or at 100 °C for 2 min. The above results were of practical significance to reveal the enzymatic browning mechanism, control the enzymatic browning and improve the quality of chrysanthemum, and can also provide the basis for the harvesting and processing of medicinal materials containing polyphenols.

This study aims to investigate the preventive effect of Dendrobium officinale in LPS-induced intestinal mucosal damage. Forty SPF-grade C57 BL/6 J male mice were randomly divided into normal group(NC), model group(LPS), and two superfine powder groups of Dendrobium officinale(DOF)(DOF-L, 0.30 g·kg~(-1)and DOF-H, 0.60 g·kg~(-1), respectively), with 10 mice in each group. DOF superfine powder suspension was given via oral administration to mice for 7 days, while the mice in NC and LPS groups received the same volume of saline for 7 days. On the eighth day, the mice in LPS group and DOF treatment groups were injected with LPS(5 mg·kg~(-1)) by intraperitoneal injection to establish the intestinal mucosal injury model, while the mice in NC group were injected with the same volume of sterile saline in the same manner. Six hours after injection with LPS or saline, plasma and the intestinal tissue were collected. The diamine oxidase(DAO) and D-lactate levels in plasma were detected with a biochemical method. The levels of proinflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in plasma were detected by ELISA. The histomorphology and ultrastructure of mouse ileum tissues were observed by hematoxylin-eosin(HE) staining in optical microscope and transmission electron microscope(TEM). The expression and distribution of tight junction(TJ) proteins claudin-1, occludin and F4/80 were detected by immunohistochemistry while the protein expression levels of Toll-like receptor 4(TLR-4) and nuclear factor kappa B p65(NF-κB p65) in jejunum were detected by Western blot. The experimental results showed that continuous intragastric administration of D. officinale superfine powder for 7 days obviously alleviated the damage and ultrastructural changes of intestinal mucosa induced by LPS; significantly decreased DAO and D-lactate levels in plasma in model group(P<0.05); up-regulated the protein expression of claudin-1 and occludin in ileum tissues; down-regulated the protein expression of TLR-4 and NF-κB p65 in jejunum tissues(P<0.01); significantly decreased TNF-α and IL-6 levels in plasma(P<0.05); and decreased the infiltration of F4/80~+ macrophage cells. Our results suggested that D. officinale had significant protective effects on LPS-induced intestinal mucosal damage and reduced intestinal permeability. The mechanism might be related to its effects of inhibiting inflammation via TLR-4/NF-κB p65, and up-regulating the expression of tight junction proteins.
Animals ; Dendrobium ; Intestinal Mucosa ; Lipopolysaccharides ; Male ; Mice ; NF-kappa B ; Powders ; Tumor Necrosis Factor-alpha/genetics*

OBJECTIVE: To screen the active components from Fuzheng Huayu Recipe (FZHY) and redesign a new recipe composed of the active components, and validate the effect of active components formulation from FZHY against liver fibrosis. METHODS: Thirty-two components from FZHY were evaluated for their activities against liver fibrosis respectively, with 6 kinds of cell models in vitro, including oxidative stressed hepatocyte in L-02, hypoxia injured/proliferative hepatic sinusoidal endothelial cells in SK-HEP-1 and human hepatic sinusoidal endothelial cells (HHSEC), and activated hepatic stellate cell in LX-2. The comprehensive activity of each component against liver fibrosis was scored according to the role of original herbs in FZHY and cell functions in fibrogenesis. Totally 7 active components were selected and combined with equal proportion to form a novel active components formulation (ACF). The efficacy of ACF on liver fibrosis were evaluated on activation of LX-2 and proliferation of HHSEC in vitro and in liver fibrosis model mice induced by dimethylnitrosamine (DMN). Totally 72 mice were divided into 6 groups using a random number table, including normal, high-dose ACF control (20 µ mol/L × 7 components/kg body weight), model, low-, medium-, high-dose ACF groups (5, 10, 20 µ mol/L × 7 components/kg body weight, respectively). Hematoxylin eosin and Sirius red stainings were used to observe inflammation and fibrosis change of liver tissue; scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were utilized to observe the effect of ACF on ultrastructure of hepatic sinusoids. RESULTS: Fifteen components from FZHY showed higher scores for their activity on against liver fibrosis. Among them, 7 components including tanshinone II A, salvianolic acid B, cordycepin, amygdalin, quercetin, protopanaxatriol, and schizandrin B were recombined with equal proportions to form ACF. ACF at 1,2, 4 µ mol/L showed strong inhibitory effects on activation of LX-2 and proliferation of HHSEC in vitro (all P<0.01). Compared with the model group, ACF attenuated liver collagen deposition, improved sinusoidal capillarization in a dose-dependent manner (all P<0.05). CONCLUSION ACF exerts a satisfactory effect against experimental liver fibrosis and attenuates sinusoidal capillarization, which warrant a further research and development for herbal components formulation on liver fibrosis.
Animals ; Body Weight ; Drugs, Chinese Herbal/adverse effects* ; Endothelial Cells ; Liver ; Liver Cirrhosis/drug therapy* ; Mice

Objective: To examine the outcomes of Slide tracheoplasty for the children with severe congenital tracheal stenosis received previous repeated balloon dilatation or metal stent placement under endoscopy. Methods: A retrospective study was conducted in 9 children with congenital tracheal stenosis undergoing previous interventional therapy under tracheoscopy and later received Slide tracheoplasty due to obvious respiratory symptoms at Department of Cardiac Surgery, Qilu Children's Hospital of Shandong University between February 2017 and July 2021. There were 7 males and 2 females with a median age at operation of 72.4 months (range: 13.3 to 98.9 months), and the median weight was 19.0 kg (range: 9.0 to 33.0 kg). Among the 9 patients, 2 patients began to receive repeated balloon dilatation (more than 3 times) 17.8 and 51.8 months ago respectively. One patient received metal stents placement into the trachea for 4 days and the other 6 children for median 56.8 months (range: 21.6 to 74.2 months). Complete tracheal cartilage rings and long segmental stenosis were present. in all 9 children. Operative details and outcome measures, including the need for endoscopic airway intervention and mortality, were collected. Results: Slide tracheoplasty was performed in all cases. Two patients with repeated balloon dilatation had different thickness of tracheal wall, local scar hyperplasia and irregular lumen. Among them, 1 case had obvious local calcification of tracheal wall, which was difficult to suture. The metal stent in one patient with short time of placement was completely removed. However, only part of the metal stents could be removed due to the long placement time in the other 6 cases. There was no operative death in the 9 children. The median postoperative tracheal intubation time was 25.3 hours (range: 17.4 to 74.5 hours). A silicone stent was placed in the trachea of 1 child due to obvious respiratory symptoms. Follow-up of median 11 months (range: 1 to 23 months) showed that no death occurred after discharge and all children had basically normal activity tolerance with no obvious respiratory symptoms. Conclusions: Slide tracheoplasty is feasible for children undergoing prior balloon dilatation or metal stents placement. Previously repeated balloon dilatation or metal stent placement under endoscopy increased the difficulty of slide tracheoplasty, the metal stent could not be completely removed after a long time.
Child ; Constriction, Pathologic ; Dilatation ; Endoscopy ; Female ; Humans ; Infant ; Male ; Reconstructive Surgical Procedures ; Retrospective Studies ; Stents ; Trachea/surgery* ; Tracheal Stenosis/surgery* ; Treatment Outcome