Ze-Qi-Tang Formula Induces Granulocytic Myeloid-Derived Suppressor Cell Apoptosis via STAT3/S100A9/Bcl-2/Caspase-3 Signaling to Prolong the Survival of Mice with Orthotopic Lung Cancer.

Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.

Analysis of "Gansu Prescriptions" in Prevention and Treatment of Coronavirus Disease-2019 / 中国实验方剂学杂志

Coronavirus disease-2019 (COVID-19) is an acute infectious disease caused by a 2019 novel coronavirus (2019-nCoV) infection. It is highly contagious, and can spread quickly home and abroad. It has caused a global pandemic. After the outbreak, Gansu province actively responded to the national "integrated Chinese and western medicine(ICWM)" epidemic prevention policy by organizing an expert group on the prevention and treatment of traditional Chinese medicine(TCM) and establishing a joint working mechanism of ICWM. In adherence to the principle of ICWM, it highlighted the advantages of TCM in epidemic prevention, and emphasized early, timely and whole course use of TCM. The expert group continued to summarize in practice and form a series of "Gansu prescriptions", so as to explore the prevention and control strategy of "prevention in advance, timely interruption and reversal, early prevention and cure, and cure in early stage". Before illness, the prevention shall be made in advance by taking Fuzheng Biwen prescription based on constitution differentiation, in order to strengthen the body resistance and removing pathogenic Qi, after the onset, the syndromes were first treated, interrupted and reversed, and Xuanfei Huazhuo prescription and Qingfei Tongluo prescription were administered based on syndrome differentiation, so as to exorcise pathogenic Qi and cure COVID-19 at the early stage, at the beginning stage of recovery, Jianpi Yifei prescription was used to strengthen the spleen and lungs, and harmonize the stomach and resolve dampness, so as to prevent recurrence. In the principle of ICWM, "Gansu prescriptions" were selected based on the constitution differentiation and syndrome differentiation, so as to prevent the occurrence of epidemics, block light and common symptoms from developing to heavy and critical symptoms, improve the clinical efficacy, shorten the course of disease, and reduce the incidence of critical illness, thereby reducing mortality.

Oyster-Derived Zinc-Binding Peptide Modified by Plastein Reaction via Zinc Chelation Promotes the Intestinal Absorption of Zinc.

Zinc-binding peptides from oyster (Crassostrea gigas) have potential effects on zinc supplementation. The aim of this study was to prepare efficient zinc-binding peptides from oyster-modified hydrolysates by adding exogenous glutamate according to the plastein reaction and to further explore the zinc absorption mechanism of the peptide-zinc complex (MZ). The optimum conditions for the plastein reaction were as follows: pH 5.0, 40 °C, substrate concentration of 40%, pepsin dosage of 500 U/g, reaction time of 3 h and l-[1-13C]glutamate concentration of 10 mg/mL. The results of 13C isotope labelling suggested that the addition of l-[1-13C]glutamate contributed to the increase in the zinc-binding capacity of the peptide. The hydrophobic interaction was the main mechanism of action of the plastein reaction. Ultraviolet spectra and scanning electronic microscopy (SEM) revealed that the zinc-binding peptide could bind with zinc and form MZ. Furthermore, MZ could significantly enhance zinc bioavailability in the presence of phytic acid, compared to the commonly used ZnSO4. Additionally, MZ significantly promoted the intestinal absorption of zinc mainly through two pathways, the zinc ion channel and the small peptide transport pathway. Our work attempted to increase the understanding of the zinc absorption mechanism of MZ and to support the potential application of MZ as a supplementary medicine.

Advances in colorectal cancer research from 2017 annual meeting of the American Society of Clinical Oncology / 中华消化外科杂志

It is plentiful about the 289 abstracts for the colorectal cancer (CRC) in the 2017 annual meeting of the American Society of Clinical Oncology (ASCO),which include:(1) comparison between long and short courses of postoperative adjuvant chemotherapy for stage Ⅲ CRC in the early diseases,applications of the full course of neoadjuvant therapy for locally advanced rectal cancer and laparoscopic total mesorectal excision for rectal cancer.(2) The use of Vitamin D3 and selective interstitial radiotherapy for metastatic CRC in the advanced diseases showed an encouraging efficacy.Patients with BRAF mutation and poor prognosis underwent a combination therapy of BRAF inhibitor and epidermal growth factor receptor (EGFR),which has created a new situation for precision therapy.And China's domestically designed Fruquintinib (small-molecule kinase inhibitor) and EGFR CMABO09 have showed better clinical efficacies in the second-line therapy.(3) On the precision medicine and translational researches,clinical value of consensus of molecular subtypes is being revealed and liquid biopsy is advantageous to predict postoperative tumor recurrence.These new therapies and researches would impact the clinical practices,promote clinical development and benefit the patients.

Effect of Eclipta prostrata on lipid metabolism in hyperlipidemic animals.

Eclipta prostrata (Linn.) Linn. is a traditional Chinese medicine and has previously been reported to have hypolipidemic effects. However, its mechanism of action is not well understood. This study was conducted to identify the active fraction of Eclipta, its toxicity, its effect on hyperlipidemia, and its mechanism of action. The ethanol extract (EP) of Eclipta and fractions EPF1-EPF4, obtained by eluting with different concentrations of ethanol from a HPD-450 macroporous resin column chromatography of the EP, were screened in hyperlipidemic mice for lipid-lowering activity, and EPF3 was the most active fraction. The LD50 of EPF3 was undetectable because no mice died with administration of EPF3 at 10.4 g/kg. Then, 48 male hamsters were used and randomly assigned to normal chow diet, high-fat diet, high-fat diet with Xuezhikang (positive control) or EPF3 (75, 150 and 250 mg/kg) groups. We evaluated the effects of EPF3 on body weight gain, liver weight gain, serum lipid concentration, antioxidant enzyme activity, and the expression of genes involved in lipid metabolism in hyperlipidemic hamsters. The results showed that EPF3 significantly decreased body-weight gain and liver-weight gain and reduced the serum lipid levels in hyperlipidemic hamsters. EPF3 also increased the activities of antioxidant enzymes; up-regulated the mRNA expression of peroxisome proliferator-activated receptor α (PPARα), low density lipoprotein receptor (LDLR), lecithin-cholesterol transferase (LCAT) and scavenger receptor class B type Ι receptor (SR-BI); and down-regulated the mRNA expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) in the liver. These results indicate that EPF3 ameliorates hyperlipidemia, in part, by reducing oxidative stress and modulating the transcription of genes involved in lipid metabolism.

Ethanol extract of Dendrobium chrysotoxum Lindl ameliorates diabetic retinopathy and its mechanism.

Diabetic retinopathy (DR) is the most common and serious complication of diabetes mellitus (DM). The present study investigates the amelioration of ethanol extract of Dendrobium chrysotoxum Lindl (DC) on streptozotocin (STZ)-induced DR and its engaged mechanism. Retinal immunofluorescence staining with cluster of differentiation 31 (CD31) demonstrated that DC (30-300 mg/kg) decreased the increased retinal vessels in STZ-induced diabetic rats. Retinal histopathological observation also showed that retinal vessels were decreased in DC-treated diabetic rats. DC decreased the increased retinal mRNA expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) in diabetic rats, and DC also decreased the elevated serum VEGF level. Immunohistochemical staining further evidenced that DC decreased VEGF and VEGFR2 expression in retinas. Retinal mRNA expression of matrix metalloproteinase (MMP) 2/9 was decreased in DC (300 mg/kg)-treated diabetic rats. Serum levels of MMP 2/9, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) A/B, insulin-like growth factor 1 (IGF-1), interleukin 1ß (IL-1ß), and IL-6 were all decreased in DC-treated diabetic rats. In addition, DC decreased the increased phosphorylation of p65 and the increased expression of intercellular adhesion molecule-1 (ICAM-1). In conclusion, DC can alleviate retinal angiogenesis during the process of DR via inhibiting the expression of VEGF/VEGFR2, and some other pro-angiogenic factors such as MMP 2/9, PDGF A/B, bFGF, IGF-1. In addition, DC can also ameliorate retinal inflammation via inhibiting NFκB signaling pathway.

[Bibenzyl from Dendrobium inhibits angiogenesis and its underlying mechanism].

Bibenzyl is a type of active compounds abundant in Dendrobium. In the present study, we investigated the inhibitory effects of six bibenzyls isolated from Dendrobium species on vascular endothelial growth factor (VEGF)-induced tube formation in human umbilical vascular endothelial cells (HUVECs). All those bibenzyls inhibited VEGF-induced tube formation at 10 micromol x L(-1) except tristin, and of which moscatilin was found to have the strongest activity at the same concentration. The lowest effective concentration of moscatilin was 1 micromol x L(-1). Further results showed that moscatilin inhibited VEGF-induced capillary-like tube formation on HUVECs in a concentration-dependent manner. Western blotting results showed that moscatilin also inhibited VEGF-induced phosphorylation of VEGFR2 (Flk-1/KDR) and extracellular signal-regulated kinase 1/2 (ERK1/2). Further results showed that moscatilin inhibited VEGF-induced activation of c-Raf and MEK1/2, which are both upstream signals of ERK1/2. Taken together, results presented here demonstrated that moscatilin inhibited angiogenesis via blocking the activation of VEGFR2 (Flk-1/KDR) and c-Raf-MEK1/2-ERK1/2 signals.

Impact of periconceptional multi-micronutrient supplementation on gestation: a population-based study / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To examine the effect of periconceptional multi-micronutrient supplementation on gestation and birth outcomes.</p><p><b>METHODS</b>A population-based community intervention program was conducted in 18 counties in China. Participants were divided into an intervention group, who received multi-micronutrient supplementation from at least 3 months before pregnancy throughout the first trimester, and a control group. Pregnant women were followed up to record information about birth outcomes. Maternal socio-economic characteristics and main birth outcomes were evaluated. Gestational age was further analyzed using survival analysis, to determine the time distribution of delivery.</p><p><b>RESULTS</b>Periconceptional multi-micronutrient supplementation was associated with higher birth weight, birth length and occipitofrontal head circumference, and with lower incidence rates for stillbirth, low birth weight, and preterm birth. Moreover, periconceptional multi-micronutrient supplementation changed the time distribution of delivery, making the deliveries more clustered in the period between day 275 and day 295 of gestation.</p><p><b>CONCLUSION</b>Our study shows that periconceptional multi-micronutrient supplementation is beneficial for fetal development and optimizes all measured aspects of health in neonates in socioeconomically disadvantaged areas in China. The change in time distribution of deliveries caused by multi-micronutrient supplementation needs further clarification.</p>

Influence of intestinal early enteral nutrition therapy on intestinal barrier function and immune response of patients with radiation enteritis / 中华放射医学与防护杂志

Objective To investigate the influence of early enteral nutrition therapy on the intestinal barrier function and immune response of the patients with radiation enteritis (ER) so as to find a relatively simple and effective method to treat RE.Methods Fifty-six patients with radiation enteritis (RE) diagnosed by colonoscopy,X-rays,and pathology were randomly divided into 2 equal groups:experimental group undergoing enteral inutrition therapy,and control group undergoing conventional therapy only.Peripheral blood samples were collected 1,11,and 21 days after admission.Plasma diamine oxidase (DAO),D-lactic acid,endotoxin,and lactulose/mannitol (L/M) ratio,and levels of IgG,IgM,and IgA,and CD4/CD8 ratio were examined.Five cases from the experimental group and 5 cases from the control group underwent second-time operation because of incomplete intestinal obstruction,intestinal stenosis,or recurrent tumor respectively.The biopsy specimens of the terminal ileum or distal descending colon taken during the first and second operations underwent pathological examination.Peripheral blood samples were collected 1,11,and 21 days after admission.Plasma diamine oxidase (DAO),D-lactic acid,endotoxin,and lactulose/mannitol (L/M) ratio,and levels of IgG,IgM,and IgA,and CD4/CD8 ratio were examined.Results There were no significant differences in the intestinal function and blood immunological indices between these 2 groups.The levels of DAO,D-lactic acid,and endotoxin,and the L/M ratio 11 days after admission of the experiment group were all significantly lower than those of the control group (t =2.568,2.427,2.143,2.443,P ＜ 0.05),and all those indices 21 days after admission of the experiment group were all much more significantly lower in comparison with the control group (t =6.019,12.834,7.837,7.997,P ＜ 0.01).The levels of IgG,IgM,and IgA,and CD4/CD8 ratio 11 days after admission of the experimental group were all significantly higher than those of the control group (t =2.096,2.211,2.182,P＜ 0.05,and t=2.301,P＜ 0.05),and the differences became much more significant 21 days after admission (t =2.703,2.679,3.138,P ＜ 0.01,and t =5.107,P ＜ 0.01).The height of the intestinal villa and the thickness of the mucosa of the specimens taken at the second-time operation were both much greater than those at the first-time operation.Conclusion Early enteral support therapy helps effectively maintain the intestinal barrier and immune response function of the RE patients.

Inhibitory effects of Sanleng pellet on angiogenesis of endometriosis in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of Sanleng pellet on angiogenesis of endometriosis in SD rats.</p><p><b>METHOD</b>The rat model of endometriosis were treated with Sanleng pellet. Observe microvessels density by immunohistochemical test as well as the expression of vascular endothelial growth factor and tumor necrosis factor-alpha in ectopic endometriotic tissue by immunohistochemical test and RT-PCR.</p><p><b>RESULT</b>Sanleng pellet can reduce MVD, and inhibit the level of protein and mRNA of vascular endothelial growth factor and TNF-alpha in ectopic endometriotic tissue.</p><p><b>CONCLUSION</b>Sanleng pellet can reduce the degree of angiogenesis in the endometriosis rats, and its mechanism might be associated with inhibiting the expression of vascular endothelial growth factor and TNF-alpha in the heterotopic tissue.</p>

Inhibitory effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer.</p><p><b>METHODS</b>In vitro, the inhibitory effects of YH-16 and 5-FU on the growth of vascular endothelial cells and colorectal cancer cells were examined by MTT assay. In vivo, colorectal cancer cells were transplanted into BALB/c mice, and the mice were divided into six groups randomly:control group, low-dose YH-16 group, middle-dose YH-16 group, high-dose YH-16 group, 5-FU group and combination group. The number of liver metastases, the size of primary tumor and the toxicity were examined after 2 weeks postoperatively. The expression of vascular endothelial growth factor (VEGF) in liver metastases was detected by immunohistochemistry, and tumor microvessel density (MVD) was measured by immunostaining with CD34 and factor VIII (monoclonal antibodies.</p><p><b>RESULTS</b>In vitro, YH-16 inhibited the growth of colon cancer cells and vascular endothelial cells, with the IC50 at (2.16+/-0.28) microg/ml and (0.64+/-0.10) microg/ml respectively. In vivo high-dose YH-16 and 5-FU had a remarkable inhibitory effect on liver metastasis, and the combination group showed significant enhancement on this effect (P< 0.05). The combination group and 5-FU group could inhibit the growth of primary tumor, but not found in YH-16 group. The toxicity of YH-16 was lower than that of 5-FU (P< 0.05), and the difference was not found in the toxicity between combination group and 5-FU group (P > 0.05). Expression of VEGF in liver metastases was clearly inhibited by YH-16 in combination with 5-FU or 5-FU alone compared to the control group, and MVD in middle-dose and high-dose YH-16 group, 5-FU group and combination group was lower than that in control group (P< 0.05).</p><p><b>CONCLUSIONS</b>The angiogenesis inhibitor YH-16 can inhibit liver metastasis of colorectal cancer through inhibiting the growth of vascular endothelial cells. YH-16 in combination with 5-FU has additive effect on inhibitory activity against liver metastasis.</p>

Comparing the effect of adjuvant chemotherapy by portal vein infusion with intraluminal chemotherapy for colorectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To compare the effect of 5-fluorouracil (5-FU) portal vein infusion (PVI) for 7 days after radical resection, with intraluminal chemotherapy during operation for eliminating liver metastasis and elevating long-term prognosis in colorectal cancer.</p><p><b>METHODS</b>162 colorectal cancer patients with radical resection were divided into portal vein chemotherapy group (group A, 82 cases) and intraluminal chemotherapy group (group B, 80 cases) randomly. In group A, 5-fluorouracil were infused with 1g per day constantly for 7 days after operation through portal vein catheters, which placed into greater omental vein and fixed on the abdominal wall. In group B, intraluminal chemotherapy was given and 5-fluorouracil 0.5 g was injected into the greater omental vein during operation.</p><p><b>RESULTS</b>The short-term complications and long-term effect in the two groups were compared by statistical software SPSS 8.0. Group A had more operative complications, and no statistical differences was found in hospital time and survival rate of the two groups. The 5-year survival rate is 76.7% (group A: 74.3%, group B: 79.2%), and the liver metastasis rate is 19.8%. There is no significant difference between the two group-survival curves. Multiple variable analysis suggested that Dukes' stage was the prognosis factor (P < 0.05).</p><p><b>CONCLUSIONS</b>The present study demonstrated that the two chemotherapy methods play an important role in preventing liver metastasis and improving the survival rate, and the intraluminal chemotherapy would be easier and simpler. The result should be further improved by using combined chemotherapy.</p>