ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside （Hyp） on lipopolysaccharide （LPS）-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L^-1 LPS or immersed in 1 g·L^-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25， 50， and 100 mg·L^-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate， malformation rate， body length， and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses， and macrophage migration was observed by fluorescence microscopy. Additionally， the mRNA levels of inflammation-related genes， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， chemokine C-C motif ligand 2 （CCL2）， chemokine C-X3-C motif receptor 1 （CX3CR1）， chemokine C-C motif receptor 2 （CCR2）， and genes associated with the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-kappa B （NF-κB） signaling pathway， were measured by Real-time quantitative polymerase chain reaction（Real-time PCR）. ResultsCompared with the pure water injection group， the model group exhibited increased mortality， malformation rates and yolk sac area ratio （P0.01）， reduced body length （P0.01）， increased total swimming distance and high-speed swimming duration （P0.01）， and up-regulated mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.01）. Hyp at low， medium and high doses， as well as aspirin， reduced the mortality and malformation rates （P0.05，P0.01）， increased the body length （P0.05，P0.01）， decreased the yolk sac area ratio （P0.01）， reduced the high-speed swimming duration （P0.01）， and down-regulated the mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.05，P0.01） compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish， thereby exerting the anti-inflammatory effect.

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

ObjectiveTo investigate the effect of Danggui Shaoyaosan （DSS） on the morphology and function of mitochondria in rats model of Alzheimer's disease （AD） and its possible mechanism. MethodRats model of AD was established by injection of streptozocin （STZ） into bilateral ventricles of SD rats. The 40 rats were randomly divided into sham group， model group， low， medium and high dosages of Danggui Shaoyaosan （12，24，36 g·kg^-1·d^-1） groups，observed the morphological changes of mitochondria in hippocampus of rats by electron microscopy after 14 days of continuous gavage. In situ end labeling（TUNEL） staining used to detect apoptosis and immunofluorescencereactive used to observe the expression of reactive oxygen species （ROS） and peroxisome proliferators-activated receptor γ coactivator lalpha （PGC-1α），quantitative Real-time polymerase chain reaction（Real-time PCR）detected the mRNA expression of dynamin-related protein 1 （Drp1），mitochondrial fusion protein 2 （MFN2） ，cytochrome C oxidase subunit Ⅳ （COX Ⅳ） and PGC-1α. Western blot detected the protein expression of adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK），phosphorylation（p）-AMPK，recombinant Sirtuin 1 （SIRT1） and PGC-1α. ResultCompared with the sham group，the results of model group showed that the damage of mitochondria in hippocampus was more obvious，accelerated the ROS production and apoptosis rate （P<0.01），decreased the mRNA level of MFN2，COX Ⅳ，PGC-1α，increased the mRNA level of Drp1，and descended the protein of p-AMPK/AMPK，SIRT1，PGC-1α （P<0.05，P<0.01）.Compared with the model group，the medium and high dose of DSS group notably improved the damage of mitochondria，reduced the production of ROS and apoptosis rate （P<0.01），promoted the mRNA expression of MFN2，COX Ⅳ，PGC-1α，inhibited the mRNA expression of Drp1，and up-regulated the protein of p-AMPK/AMPK，SIRT1，PGC-1α （P<0.01）. ResultDSS can significantly ameliorate the mitochondrial homeostasis imbalance in AD rats.

: ,Objective To analyze the current status and development trends of the patents of spleen-invigorating health food with the homology of medicine and food in China, and to provide ideas and references for the research and development of traditional Chinese medicine (TCM) spleen-invigorating health food with the homology of medicine and food. Methods: The State Administration for Market Regulation website’s “Special Food Information Query Platform” and the incoPat global patent database were searched in this study. Based on the methods of bibliometrics, the registered health food and patents related to spleen-invigorating health food with the homology of medicine and food in China were sorted out. Furthermore, the research and development numbers, provinces, institutions, technology and efficacy classification, major drugs, active ingredients and others of invigorating spleen health food in China were analyzed, and filtered patent data were visualized and analyzed by R programming language and CytoScape software. Results: A total of 285 patents of health food with the homology of medicine and food for invigorating spleen were included and analyzed. From 2012, the patent registration numbers of these spleen-invigorating health food with the homology of medicine and food increased significantly in China. Over the past 20 years, the top five provinces in terms of patent disclosures were Guangdong, Anhui, Jiangsu, Shandong, and Guangxi. It was found that the technical efficacy of over 20 patents was described as “immune enhancement” “digestion” “disease prevention”, etc. Patent applications were mainly aimed at the research and development of the preservation of food or ingredients, the specific therapeutic activity of compounds, and pharmaceutical preparations, which were led by corporation research and development registrations, and supplemented by applications from research institutions and individuals. Among the 285 patents, the top 10 raw materials of spleen-invigorating health food with the homology of medicine and food were Shanyao (Dioscoreae Rhizoma), Fuling (Poria), Shanzha (Crataegi Fructus), Baizhu (Atractylodis Macrocephalae Rhizoma), Chenpi (Citri Reticulatae Pericarpium), Dazao (Jujubae Fructus), Gancao (Glycyrrhizae Radix et Rhizoma), Fengmi (Mel), Maiya (Hordei Fructus Germinatus), and Dangshen (Salviae Miltiorrhizae Radix et Rhizoma). The main functions were to nourish spleen and replenish Qi, invigorate spleen and benefit lungs, nourish blood and promote fluid production, and nourish spleen and stomach. Conclusion The main drug composition and functional components of spleen-invigorating health food with the homology of medicine and food are relatively clear, and the technical effects of invigorating the spleen and stomach, eliminating accumulation of food, and enhancing immunity are highly targeted. This paper provides evidence for the research and development, mechanism research, and process improvement of spleen-invigorating health food with the homology of medicine and food in the future.

Objective: To study the mechanism of action of Danggui Shaoyao San (DSS) in the treatment of Alzheimer'sdisease (AD) from a systematic network level using network pharmacology. Methods: The active ingredients of DSS intreating AD was screened from the Traditional Chinese Medicine System Pharmacology Database (TCSMP), and thedrugs-targets-disease network was built. Target organ localization network, GO analysis and Pathway enrichmentanalysis were used for bioinformatics analysis. Results: 51 kinds of DSS active ingredients were screened by networkpharmacology, showing 377 predicted targets of active compounds. Among them, 197 targets were associated with AD, and the pharmacodynamic targets of DSS active compounds were highly enriched with AD-related signals. The pathwaywas closely related to the reduction of Aβ aggregation and inhibition of tau hyperphosphorylation and biological processessuch as anti-inflammatory and anti-apoptosis, and the mRNA expression of the targeted gene was mainly enriched in theliver, heart, and brain. Conclusion: DSS active compounds interact with multiple targets in multiple ways in a synergisticmanner, mainly to produce important therapeutic effects on AD with anti-inflammatory, anti-apoptotic, enhancingmetabolism and immune system.

Objective To analyze the clinical efficacy,toxicity and survival prognosis of patients diagnosed with Siewert type Ⅱ and Ⅲ locally advanced adenocarcinoma of esophagogastric junction (AEG) undergoing preoperative involved-field irradiation with concurrent chemotherapy. Methods A total of 45 cases were recruited in this prospective clinical trial. Prior to surgery, patients received 2 cycles of chemotherapy with XELOX and concurrent radiotherapy ( a total of 45 Gy in 25 fractions,5 times weekly). After 6-8 weeks,they underwent surgical resection. After the surgery,patients received 6 cycles of adjuvant chemotherapy. The completion of preoperative neoadjuvant chemoradiotherapy, postoperative pathological status,TNM down-staging effect and adverse reactions were observed. Kaplan-Meier method was applied to estimate survival analysis. Results All 45 patients completed preoperative neoadjuvant chemoradiotherapy. Among them, 39 patients completed 2 cycles of chemotherapy, and 6 patients completed 1 cycle of chemotherapy. The median time of surgical interval was 6 weeks. The R0resection rate was 96%.The pathological complete response (pCR) rate was 22%. The TNM down-staging rate was 69%.The incidence of acute radiation-induced esophagitis or gastritis was 44% and the incidence of radiation-induced pneumonitis was 7%. The incidence of grade 1-3 leukocytopenia,thrombocytopenia and neutropenia was 78%,47% and 44%,respectively. In terms of gastrointestinal reactions,the incidence of nausea,vomiting and loss of appetite was 62%,24% and 71%,respectively. No hematologic or nonhematologic adverse effects was observed at grade 4 or 5.The median follow-up time was 30 months. 11 patients died of cancer,1 patient was treatment-related death in the perioperative period and 1 patient died of pneumonia. The 1-,2-and 3-year progression-free survival (PFS) rates were 90%,70% and 67%,respectively. The 1-,2-and 3-year overall survival rates were 95%,80% and 75%,respectively. The 1-,2-and 3-year local control rates were 95%,84% and 84%, respectively. The 1-, 2-and 3-year distant metastasis rates were 7%, 25% and 25%, respectively. Conclusions Preoperative involved-field irradiation with concurrent chemotherapy yields relatively high clinical efficacy and is well tolerated by patients with Siewert typeⅡandⅢlocally advanced AEG.Patients are recommended to receive 4 cycles of adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery.

Objective To examine the effects of different pre-treatment nutritional status and inflammatory markers on acute adverse reactions in esophageal cancer patients during concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy.Methods The acute adverse reactions of 338 eligible esophageal cancer patients who received concurrent IMRT and chemotherapy in our hospital from 2006 to 2014 were reviewed.The effects of different pre-treatment nutritional status, such as body mass index level (BMI), albumin level (ALB), total lymphocyte count (TLC), the presence or absence of anemia, and inflammatory indicators including neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), on acute adverse reactions in the patients were examined.Data were analyzed using the chi-square test with continuity correction and logistic regression analysis.Results The incidence rate of malnutrition in the patients based on their nutritional status was 5.62%-54.14%.The incidence rate of grade≥2 acute radiation esophagitis (RE) was significantly higher in the low ALB group than in the normal ALB group (P=0.000).The incidence rate of adverse reactions in the hematologic system increased as TLC decreased (P=0.006), but the incidence rate of acute radiation pneumonitis (RP) was reduced as TLC decreased (P=0.001).In addition, the incidence rate of grade ≥2 acute RE was significantly higher in the anemia group than in the non-anemia group.Inflammatory marker analysis demonstrated that the incidence rate of acute RE was significantly higher in the high NLR group and high PLR group than in the low NLR group and low PLR group (P=0.000 and P=0.024, respectively).Logistic regression analysis of nutritional status and inflammatory markers showed that TLC was an independent risk factor for acute adverse reactions in the hematologic system (P=0.001), and ALB and PLR were independent risk factors for acute RE (P=0.017 and P=0.011,respectively).Conclusions Nutritional status and inflammatory markers are associated with concurrent chemoradiotherapy-induced acute adverse reactions in esophageal carcinoma patients, and hence may be valuable indicators of acute adverse reactions during treatment.In addition, nutritional treatment and support care should be actively provided to the patients to prevent the development of acute adverse reactions during treatment.

Aim To investigate the effects of Naotai formula extract(NTE)on the expression of heme oxygenase-1(HO-1) and hephaestin(Heph) in hippocampus of rats after cerebral ischemia/reperfusion by Keap1-Nrf2/ARE signaling pathway.Methods Eighty rats were randomly divided into five groups as follows: sham operation group(Sham), cerebral ischemia/reperfusion group(I/R), low dose group of NTE(4.5 g·kg-1), middle dose group of NTE (9 g·kg-1) and high dose group of NTE(18 g·kg-1).Rats were pretreated by intragastric administration for three consecutive days, and then subjected to middle cerebral artery occlusion (MCAO) 2 hours before reperfusion.The rats were administered with intragastric administration for two days.After cerebral ischemia reperfusion 72 hours, the behavioral activity of rats was recorded by Zea Longa neurological score, and the infarct volume was measured by TTC staining.The expressions of Nrf2, HO-1 and Heph in hippocampus of cerebral ischemia reperfusion rats were observed by real-time quantitative PCR and Western blot, respectively.Results Compared with model group, the neurobehavioral scores significantly decreased in NTE high-dose and middle-dose groups (P<0.01);the infarct volume of NTE groups markedly decreased (P<0.01);the expression of HO-1 mRNA apparently increased (P<0.05) in NTE groups;the expression of Heph mRNA significantly increased in NTE middle-dose and high-dose groups (P<0.05);the expression of Nrf2 and Heph protein evidently increased in the NTE middle and high dose groups (P<0.05, P<0.01);and the expression of HO-1 protein also increased in NTE groups(P<0.01).Conclusions Naotai formula can relieve cerebral ischemia-reperfusion injury.The mechanism might be associated with activating Keap1-Nrf2/ARE signaling pathways, promoting HO-1 generation, advancing the expression of Heph, and then reducing brain iron deposition, to achieve the protection of neurons after cerebral ischemia-reperfusion.

postoperative pathological examination results and radiotherapy toxicities. Results All the 45 patients completed preoperative concurrent chemoradiotherapy and surgery, with two cycles of chemotherapy in 39 patients and one cycle in 6 patients. The rates of R0resection and pathological complete response(pCR) were 95.6%(43/45)and 22.2%(10/45), respectively. There were 10(22.2%), 17(37.8%), 15 (33.3%),and 3(6.7%)patients with tumor regression grades 0,1,2,3,respectively. The rate of lymph node metastasis was 37.8%(17/45),and the lymph node ratio was 4.33%(46/1 062). The postoperative pathological examination showed that T and N downstaging after surgery was observed in 24 and 26 patients, respectively;the proportions of patients with T3-T4tumors and positive lymph nodes after surgery declined by 51.1%(P=0.000)and 42.2%(P=0.000), respectively. The overall incidence of radiation esophagitis/gastritis was 44.4%(20/45), and the incidence rates of grade 1, 2, and 3 radiation esophagitis/gastritis were 18%,22%,and 4%,respectively. The incidence of acute radiation pneumonitis was 6.7%(3/45), all in grades 1 and 2. There was one perioperative treatment-related death. Conclusions Two cycles of XELOX chemotherapy combined with concurrent 45 Gy radiotherapy before surgery in patients with locally advanced Siewert type Ⅱ and Ⅲ AEG can achieve a relatively high pCR rate,effectively reduce the lymph node metastasis rate, achieve downstaging, and increase R0resection rate. This regimen has many good advantages,including low incidence of acute toxicities,good tolerability,and acceptable rate of perioperative treatment-related deaths. The target volume delineation involving metastatic lymph nodes is feasible.

Objective To investigate the clinical effect of induction chemotherapy plus concurrent radiochemotherapy in the treatment of locally advanced non-small cell lung cancer (NSCLC) through a meta-analysis.Methods CBM, CNKI, Cochrane Library, PubMed, and EMbase were searched for the articles on comparison between induction chemotherapy plus concurrent radiochemotherapy and concurrent radiochemotherapy for patients with locally advanced NSCLC.According to the inclusion and exclusion criteria, the data on short-term outcome and survival were collected.A Meta-analysis was performed to evaluate the clinical effect of induction chemotherapy followed by concurrent radiochemotherapy.Results A total of 5 articles were included, which involved 845 patients.The results showed that the short-term outcome and the 2-and 3-year survival rates were similar between patients receiving induction chemotherapy plus concurrent radiochemotherapy and those receiving concurrent radiochemotherapy ( OR=0.875, 95% CI 0.507-1.510, P=0.631;HR=0.770, 95% CI 0.515-1.151, P=0.203;HR=0.809, 95% CI 0.559-1.172, P=0.262), but the patients receiving induction chemotherapy plus concurrent radiochemotherapy showed a significantly higher incidence rate of grade ≥ 3 leukopenia than those receiving concurrent radiochemotherapy alone ( OR=0.637, 95% CI 0.435-0.931, P=0.020).Conclusions Induction chemotherapy plus concurrent radiochemotherapy shows no significant advantages over concurrent radiochemotherapy alone in the short-term outcome and 2-and 3-year survival rates, but it significantly increases myelosuppression.Since there are few studies involving a limited number of cases included in this analysis, more multicenter randomized trials are needed to provide more detailed data and further clarify the clinical value of induction chemotherapy plus concurrent radiochemotherapy.