Research on anti-tumor mechanism of attenuated Salmonella typhimurium VNP20009 / 药学学报

Attenuated Salmonella typhimurium VNP20009 is a widely used natural oncolytic bacterium, which has great application potential given its unique characteristics, including clinical safety, tumor targeting specificity, and explicit genome sequence. Here, we show that tumor progression can be effectively reduced by intraperitoneal administration with VNP20009 in a mouse model of melanoma (all animal experiments were conducted in accordance with the Animal Ethics Committee of China Pharmaceutical University); co-culture experiment in vitro demonstrated that VNP20009 can induce the polarization of macrophage M1, accompanied by expression of inflammation-related factors; flow cytometry analysis showed that VNP20009 induced the increase of immune cell infiltration in tumor. Further analysis showed that T cells infiltration in tumor-draining lymph node (TDLN) increased, and VNP20009 induced the activation of CD4+ T cells and CD8+ T cells in tumor. Our results demonstrate that VNP20009 treatment significantly inhibited melanoma tumors by remodeling tumor-associated macrophages to an M1-like phenotype, as well as recruiting and activating cytotoxic T cells, combined with its own antigenic activity to exert anti-tumor immunity.

Mechanism of active ingredients in Periploca forrestii compound against rheumatoid arthritis based on integrative metabolomics and network pharmacology / 中国中药杂志

In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.

Clinical Trial of Acupuncture Treatment of Gastroesophageal Reflux Disease Accompanied with Somnipathy at Acupoints of Governor Vessel at Back Segment / 针刺研究

OBJECTIVE: To observe the curative effect of needling stimulation of the back segment (10 spots below the spinous processes from T 3 to T 12)of the Governor Vessel in the treatment of gastroesophageal reflux disease(GERD)accompanied with somnipathy. METHODS: A total of 58 patients of GERD accompanied with somnipathy were randomly divided into acupuncture group (n＝28) and medication group (n＝30)according to random number table method. For patients of the acupuncture group, the spots below the spinous processes from T 3 to T 12, including acupoints Shenzhu (GV 12), Shendao (GV 11), Lingtai (GV 10), Zhiyang (GV 9), Jinsuo (GV 8), Zhongshu (GV 7) and non-acupoints (T 4, T 8, T 12) were punctured with filiform needles, once every other day for 8 weeks. Patients of the medication group were ordered to take Omeprazole capsules (20 mg/time), twice a day for 8 weeks. The therapeutic effect was assessed by "Reflux Diagnostic Questionnaire" (RDQ，scores of symptoms of heartburn, retrosternal pain, acid regurgitation and food regurgitation, 0－40 points), GERD symptom scale (scores of symptoms of the digestive system, five-sense organs, cardiovascular system, etc., 0－84 points) and Pittsburgh Sleep Quality Index (PSQI, scores of sleep quality, fall asleep time, sleep duration, sleep efficiency, etc., 0－21 points), respectively. RESULTS: After the treatment, RDQ score, GERD symptom scale score and PSQI score were significantly decreased in both acupuncture and medication groups compared with their own pre-treatment(P<0.01), and the decreased scores of RDQ, GERD scale and PSQI were significantly lower in the acupuncture group than in the medication group (P<0.01). The cured plus markedly effective rates for RDQ in the two groups were 43.3% (13/30) and 71.4% (20/28), respectively, and the effective rates of the medication and acupuncture groups were 56.7% (17/30) and 89.3% (25/28) for GERD scale, and 60.0% (18/30) and 92.9% (26/28) for PSQI, respectively. The cured plus markedly effective rate for RDQ, and the effective rates for GERD scale and PSQI were signi-ficantly higher in the acupuncture group than in the medication group respectively (P<0.05，P<0.01)．. CONCLUSION: Acupuncture stimulation of acupoints of Governor Vessel at the back segment is effective in improving symptoms of GERD patients with somnipathy.

Chemical constituents from Pachysandra terminalis / 中国中药杂志

To study chemical constituents from Pachysandra terminalis. By repeated column chromatography, including silica gel, Toyopearl HW-40, and preparative HPLC, four new (14) and one known (5) compounds were isolated and purified. On the basis of spectral data analysis, the structure of isolated compounds were elucidated as follow: 2-methyl-3-methylenepentane-1, 2, 5-triol (1), 4-methyl-3-methylenepentane-1, 2, 5-triol (2), 4-methyl-3-methylenepentane-1, 2, 5-triol-5-O-beta-D-glucopyranoside (3), 4-methyl-3-methylenep- entane-1, 2, 5-triol-1-O-beta-D-glucopyranoside (4), (7S, 8R, 8' R)-(+)-lariciresinol-9-O-beta-D-glucopyrano-side (5). Compound 5 was isolated from this genus for the first time.

Epidemiological study of the effects of smoking cigarette on thyroid gland / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the effect of cigarette smoking on thyroid gland volume, thyroid function and thyroid autoantibodies in the areas with different iodine intakes.</p><p><b>METHODS</b>A cross-sectional epidemiological study in Panshan (mild iodine-deficient area), Zhangwu (more than adequate iodine intake area) and Huanghua (iodine-excessive area) was conducted in 3761 subjects in 1999.80.2 % of them were followed up in 2004. Questionnaires, thyroid function, thyroid autoantibodies, urinary iodine concentration,and thyroid B ultrasound were performed.</p><p><b>RESULTS</b>The prevalence of goiter was higher in smokers than in non-smokers (15.1% vs. 11.5%, P< 0.05). The average thyroid volume was higher in smokers with phenomenon more obvious in Panshan and Huanghua areas. Data from logistic analysis showed that smoking cigarette was an independent risk factor of goiter. There was no difference in serum TSH and Tg level between smokers and non-smokers. The positive rate of TPOAb (>100 IU/ml) was higher in smokers than in non-smokers(10.8% vs. 9.0 % , P <0.05) and was especially obvious in Huanghua area. Smoking was a independent risk factor of increasing positive rate of TPOAb. During the prospective observation,it was found that the incidence of positive TPOAb(>,100 IU/ml) was 7.4% in the subjects that were from non-smokers turning to smokers and 2.9% in those whose smoking behavior did not change. Logistic analysis indicated that the shifting from non-smoking to smoking was independent risk factor for the increase on high incidence of positive TPOAb.</p><p><b>CONCLUSION</b>Smoking cigarette was a independent risk factor of goiter. Smoking was also a risk factor of increasing TPOAb positive rate. Shifting from not smoking to smoking was an independent risk factor of increasing high incidence of positive TPOAb.</p>

Thyroid autoantibodies In a five-year follow-up survey of populations with different Iodine intakes / 中华内分泌代谢杂志

Objective To perform a follow-up survey about thyroid disorders in three rural communities with different iodine intakes in China,observe the incidences and natural outcomes of positive thyroid autoantibodies in euthyroid population,and also explore the influence of iodine intakes on these outcomes and autoantibodies.Methods In 1999,a cross-sectional study on thyroid disorders was performed in three rural communities of Pansan ( mild iodine deficient area),Zhangwu ( more than adequate iodine intake area) and Huanghua (excessive iodine intake area) in China.The 5-year follow-up study was performed in 2004.Both in 1999 and 2004,serum levels of TSH,thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were measured with the same method.Iodine in urine and B ultrasound on thyroid were also examined.Results Among the euthyroid subjects with normal TSH level in 1999,an increased prevalence of positive TPOAb in Zhangwu and an increased prevalence of positive TgAb in Hnanghua were observed in 2004 (both P＜0.05 ).Most of euthyroid subjects with positive TPOAb or positive TgAb in 1999 remained positive thyroid antibodies in 2004. The percentage was even higher in those with high levels of antibodies.Thyroid dysfunction was more frequent in subjects with positive TPOAb and/or TgAh than in those without thyroid antibodies (14.44% vs 3.11%,P＜0.01).For those with positive antibodies in 1999,the incidence of hypothyroidism in 2004 was 1.32%,8.46% and 15.38% in Pansan,Zhangwu and Huanghua,respectively (P＜0.05).The 5-year cumulative incidences of positive TPOAb (≥50 U/ml) and TgAb (≥40 U/ml) were 2.81% and 3.82%,respectively.The incidence of positive TPOAb was the highest in Zhangwu ( 3.84% ).The incidence of positive TgAb was the highest in Huanghua (5.07%),significantly higher than those in other two areas (P＜0.05).Conclusion The incidence of thyroid dysfunction is higher in subjects with positive antibodies than that in those with negative antibodies.The high iodine intake is a risk factor of hypothyroidism in subjects with positive thyroid antibodies.Sustained excessive iodine intake increases the incidence of positive thyroid antibodies.