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We present the application of N -difluoroacetylglucosamine (GlcNDFA) in a chemical evolution strategy to synthesize oligosaccharides. In comparison to conventional N -trifluoroacetylglucosamine, GlcNDFA exhibits superior substrate compatibility with glycosyltransferases as well as stability in aqueous environments. Using our 16-step assembly line, GlcNDFA can be used to produce homogeneous dekaparin, a heparin-like medication, with a yield of 62.2%. This underscores the significant potential of GlcNDFA as a chemical evolution precursor in the precise synthesis of structurally defined polysaccharides.

Heparin is an important anticoagulant drug, and microbial heparin biosynthesis is a potential alternative to animal-derived heparin production. However, effectively using heparin synthesis enzymes faces challenges, especially with microbial recombinant expression of active heparan sulfate N-deacetylase/N-sulfotransferase. Here, we introduce the monosaccharide N-trifluoroacetylglucosamine into Escherichia coli K5 to facilitate sulfation modification. The Protein Repair One-Stop Service-Focused Rational Iterative Site-specific Mutagenesis (PROSS-FRISM) platform is used to enhance sulfotransferase efficiency, resulting in the engineered NST-M8 enzyme with significantly improved stability (11.32-fold) and activity (2.53-fold) compared to the wild-type N-sulfotransferase. This approach can be applied to engineering various sulfotransferases. The multienzyme cascade reaction enables the production of active heparin from bioengineered heparosan, demonstrating anti-FXa (246.09 IU/mg) and anti-FIIa (48.62 IU/mg) activities. This study offers insights into overcoming challenges in heparin synthesis and modification, paving the way for the future development of animal-free heparins using a cellular system-based semisynthetic strategy., (© 2024. The Author(s).)

Currently, natural products are one of the priceless options for finding novel chemical pharmaceutical entities. Ellipticine is a naturally occurring alkaloid isolated from the leaves of Ochrosia elliptica Labill. Ellipticine and its derivatives are characterized by multiple biological activities. The purpose of this review was to provide a critical and systematic assessment of ellipticine and its derivatives as bioactive molecules over the last 60 years. Publications focused mainly on the total synthesis of alkaloids of this type without any evaluation of bioactivity have been excluded. We have reviewed papers dealing with the synthesis, bioactivity evaluation and mechanism of action of ellipticine and its derivatives. It was found that ellipticine and its derivatives showed cytotoxicity, antimicrobial ability, and anti-inflammatory activity, among which cytotoxicity toward cancer cell lines was the most investigated aspect. The inhibition of DNA topoisomerase II was the most relevant mechanism for cytotoxicity. The PI3K/AKT pathway, p53 pathway, and MAPK pathway were also closely related to the antiproliferative ability of these compounds. In addition, the structure-activity relationship was deduced, and future prospects were outlined. We are confident that these findings will lay a scientific foundation for ellipticine-based drug development, especially for anticancer agents., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Sanguinarine is a quaternary ammonium benzophenanthine alkaloid found in traditional herbs such as Chelidonium, Corydalis, Sanguinarum, and Borovula. It has been proven to possess broad-spectrum biological activities, such as antitumor, anti-inflammatory, antiosteoporosis, neuroprotective, and antipathogenic microorganism activities. In this paper, recent progress on the biological activity and mechanism of action of sanguinarine and its derivatives over the past ten years is reviewed. The results showed that the biological activities of hematarginine and its derivatives are related mainly to the JAK/STAT, PI3K/Akt/mTOR, NF-κB, TGF-β, MAPK and Wnt/β-catenin signaling pathways. The limitations of using sanguinarine in clinical application are also discussed, and the research prospects of this subject are outlined. In general, sanguinarine, a natural medicine, has many pharmacological effects, but its toxicity and safety in clinical application still need to be further studied. This review provides useful information for the development of sanguinarine-based bioactive agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Natural products are treasure houses for modern drug discovery. Diphyllin is a natural arylnaphthalene lignan lactone isolated from the leaf of Astilboides tabularis . Studies have found that it possesses plenty of bioactivity characteristics. In this paper, we reviewed the structure, bioactivity, and mechanism of action of diphyllin and its derivatives. The references were obtained from PubMed, Web of Science, and Science Direct databases up to August 2023. Papers without a bio-evaluation were excluded. Diphyllin and its derivatives have demonstrated V-ATPase inhibition, anti-tumor, anti-virus, anti-biofilm, anti-inflammatory, and anti-oxidant activities. The most studied activities of diphyllin and its derivatives are V-ATPase inhibition, anti-tumor activities, and anti-virus activities. Furthermore, V-ATPase inhibition activity is the mechanism of many bioactivities, including anti-tumor, anti-virus, and anti-inflammatory activities. We also found that the galactosylated modification of diphyllin is a common phenomenon in plants, and therefore, galactosylated modification is applied by researchers in the laboratory to obtain more excellent diphyllin derivatives. This review will provide useful information for the development of diphyllin-based anti-tumor and anti-virus compounds.

The efficiency of de novo synthesis of hyaluronic acid (HA) using Pasteurella multocida hyaluronate synthase (PmHAS) is limited by its low catalytic activity during the initial reaction steps when monosaccharides are the acceptor substrates. In this study, we identified and characterized a β-1,4-N-acetylglucosaminyl-transferase (EcGnT) derived from the O-antigen gene synthesis cluster of Escherichia coli O8:K48:H9. Recombinant β1,4 EcGnT effectively catalyzed the production of HA disaccharides when the glucuronic acid monosaccharide derivative 4-nitrophenyl-β-D-glucuronide (GlcA-pNP) was used as the acceptor. Compared with PmHAS, β1,4 EcGnT exhibited superior N-acetylglucosamine transfer activity (~ 12-fold) with GlcA-pNP as the acceptor, making it a better option for the initial step of de novo HA oligosaccharide synthesis. We then developed a biocatalytic approach for size-controlled HA oligosaccharide synthesis using the disaccharide produced by β1,4 EcGnT as a starting material, followed by stepwise PmHAS-catalyzed synthesis of longer oligosaccharides. Using this approach, we produced a series of HA chains of up to 10 sugar monomers. Overall, our study identifies a novel bacterial β1,4 N-acetylglucosaminyltransferase and establishes a more efficient process for HA oligosaccharide synthesis that enables size-controlled production of HA oligosaccharides. KEY POINTS: • A novel β-1,4-N-acetylglucosaminyl-transferase (EcGnT) from E. coli O8:K48:H9. • EcGnT is superior to PmHAS for enabling de novo HA oligosaccharide synthesis. • Size-controlled HA oligosaccharide synthesis relay using EcGnT and PmHAS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Our study aimed to investigate the role of lncRNA-Neighboring Enhancer of FOXA2 (NEF) in esophageal squamous-cell carcinoma., Patients and Methods: Tumor tissues and adjacent tissues were obtained from esophageal squamous-cell carcinoma patients, and blood samples were extracted from both patients with esophageal squamous-cell carcinoma and healthy volunteers. The expression of NEF was detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). All patients were followed-up for 5 years and ROC curve analysis and survival analysis were performed to evaluate the diagnostic and prognostic values of serum NEF for esophageal squamous-cell carcinoma. NEF expression vector was transfected into cells of esophageal squamous-cell carcinoma cell lines. Cell proliferation, migration and invasion were detected by CCK-8 assay, transwell migration assay, and transwell invasion assay, respectively. The interaction between NEF and wnt/β-catenin pathway were explored by Western blot and qRT-PCR., Results: Expression of NEF was significantly downregulated in tumor tissues than in adjacent tissues in most patients. Serum level of NEF was higher in esophageal squamous-cell carcinoma patients than in healthy controls, and was significantly correlated with tumor size and tumor distant tumor metastasis. Serum NEF is a promising diagnostic and prognostic marker for esophageal squamous-cell carcinoma. NEF overexpression inhibited cancer cell proliferation, migration and invasion. NEF overexpression decreased the expression levels of wnt/β-catenin pathway-related proteins, while Wnt activator showed no significant effects on NEF. However, Wnt inhibitor reduced the effects of NEF overexpression on cell proliferation, migration and invasion., Conclusions: LncRNA NEF may inhibit the proliferation, migration and invasion of esophageal squamous-cell carcinoma cells by inactivating with wnt/β-catenin pathway.

Winter wheat and summer maize were the main crops in the North China Plain. While intensive farming system could generally achieve high yield, the perennial large amounts of nitrogen (N) fertilization application cause environmental problems including NO 3 - -N accumulation and leaching at deep soil layer. Here, the effects of different N application rates on soil NO 3 - -N accumulation and leaching in winter wheat-summer maize cropping system were investigated from 2010 to 2016 at Qingyuan County, Hebei Province, China. There were five treatments with N application rates at 0 (N 0 ), 100 (N 100 ), 180 (N 180 ), 255 (N 255 ) and 330 (N 330 ) kg·hm -2 . Results showed that crop yield and soil N status significantly varied among treatments for both wheat and maize after each harvest, respectively. Soil NO 3 - -N were accumulated during winter wheat growing season and leached to deeper soil during summer maize growing season. Moreover, the soil NO 3 - -N accumulation amount in the 90 to 180 cm soil profile decreased with the decreases of N inputs (N 330 > N 255 > N 180 > N 100 > N 0 ). Soil NO 3 - -N could be leached to 990 cm soil depth. There were six NO 3 - -N accumulation peaks in the soil profile, with the peaks presenting at deeper soil profile with higher N fertilization rate. The deepest peak appeared at 840 cm soil depth with the N application rate of 330 kg·hm -2 . From the distribution of NO 3 - -N accumulation in the soil profile, only around 10% of total NO 3 - -N was accumulated between 0-90 cm soil depth, while the rest accumulated below 90 cm, which could not be largely absorbed by plants. Therefore, NO 3 - -N leaching during summer maize growing season was serious and it was greater with higher N fertilization rate which might lead to increased risk of underground water contamination. In terms of balanced crop yield and soil NO 3 - -N accumulation, the rate of 180 kg·hm -2 would be the optimum one in areas with similar cultivation and environmental conditions to the present study.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. Epstein-Barr virus (EBV) infection plays a fundamental role in NPC development with the mechanism is not well understood. Here we demonstrate that EBV oncoprotein LMP1 drives EMT and metastasis of NPC by reactivating the adhesion molecule, cadherin 6 (CDH6), which normally occurs in embryogenesis with unknown role in NPC. CDH6 was found to be upregulated in LMP1-positive NPC tissues, and was identified as a target of the epithelium-specific miR-203. LMP1-activated NF-κB transcriptionally repressed the miR-203 expression by binding to the promoter region of miR-203 gene. CDH6 activation in turn induced EMT and promoted metastasis in NPC. CDH6 depletion, NF-κB inhibitor and miR-203 overexpression were able to impair the EMT effects. The miR-203 downregulation in NPC tissues was strongly associated with metastasis clinically. The CDH6 activator, Runt-related transcription factor 2 (RUNX2), was also activated by EBV in the event. For both CDH6 and RUNX2 are components at TGF-β downstream, CDH6 became a node protein for the interplay of multiple signalings including NF-κB and TGF-β. Therefore, the switch-on of miR-203 was important for nasopharyngeal epithelial cells to maintain normal phenotype. This study demonstrates that EBV has evolved sophisticated strategies by driving epithelial cells to obtain malignant features, particularly in NPC metastasis, providing novel biomarkers for the therapy and prognosis of EBV-associated NPC.

Perfect matching of an assembled physical sequence to a specified designed sequence is crucial to verify design principles in genome synthesis. We designed and de novo synthesized 536,024-base pair chromosome synV in the "Build-A-Genome China" course. We corrected an initial isolate of synV to perfectly match the designed sequence using integrative cotransformation and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated editing in 22 steps; synV strains exhibit high fitness under a variety of culture conditions, compared with that of wild-type V strains. A ring synV derivative was constructed, which is fully functional in Saccharomyces cerevisiae under all conditions tested and exhibits lower spore viability during meiosis. Ring synV chromosome can extends Sc2.0 design principles and provides a model with which to study genomic rearrangement, ring chromosome evolution, and human ring chromosome disorders., (Copyright © 2017, American Association for the Advancement of Science.)

To observe the functions of Gualou Xiebai Banxia decoction（GXBD） on regulating lipid metabolism, anti-oxidation, and interposing ox-LDL/Lox-1 pathway, and to explore its anti-atherosclerosis (AS) mechanisms. AS models were established by using 42 Apo-E-/- male mice with high fat diet. AS model mice were randomly divided into the model group, simvastatin group, and GXBD high and low dose groups. C57BL/6J male mice were used as the normal control group, n=10 and the treatment lasted for 8 weeks. The levels of TC, TG, LDL-C, HDL-C, SOD, MDA, GSH-px, and ox-LDL in blood serum were tested 24 h after the last administration. The changes of aortic tissues structure were observed by HE staining; the expression levels of Lox-1 protein and the expression levels of mRNA were detected by Western blot and PCR respectively.Results showed that the blood lipid levels and MDA, ox-LDL levels in blood serum of model group were significantly higher than those in the normal control group, but SOD, GSH-px levels were significantly lower than those in the normal control group, and the Lox-1 protein and mRNA expression levels were also significantly higher than those in the control group(P<0.05), namely aortic atherosclerosis lesions were obvious in model group.The levels of blood lipid and MDA, ox-LDL of GXBD high and low dose groups and simvastatin group were significantly lower than those in model group, while SOD, GSH-px levels were significantly higher than those in model group, and Lox-1 protein and mRNA expression levels were significantly lower than those in model group(P<0.05), namely the aortic atherosclerosis lesions were significantly relieved. The above results indicated that GXBD was capable of modulating blood lipid, anti-oxidation, and inhibiting the expression of Lox-1, and interposing ox-LDL/Lox-1 pathway in the AS model Apo-E-/- mice, which may be one of the mechanisms of anti-atherosclerosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To investigate the effect of direct moxibustion at Ganshu (BL18) on the serum concentrations of tumor specific growth factor (TSGF) and tumor necrosis factor α (TNF-α) in a rat model with precancerous lesion of primary hepatocellular carcinoma (HCC), so as to explore the mechanism of moxibustion underlying improvement of HCC., Methods: Sixty male Wistar rats were randomly divided into control group (n=10), model group (n=20), prevention group 1 (n=15) and prevention group 2 (n=15). The normal rats were injected with physiological saline as blank control. At the same time, the rats of other three groups were injected with diethylnitrosamine to establish the HCC model. Direct moxibustion with grain-sized moxa was applied to bilateral Ganshu acupoint of the rats in the prevention group 1 (1 treatment course, 20 days) and prevention group 2 (2 treatment courses, 40 days), 5 doses for each acupoint, 0.5 mg/dose, once every other day. At each time point (before model establishment, the end of 1st course prevention, the end of 2nd course prevention and the end of model establishment), serum levels of TSGF and TNF-α were detected using enzyme-linked immunosorbent assay., Results: Compared with the control group, there was a remarkably increase of serum TSGF and TNF-α contents in the model group at the end of the experiment (P<0.05). At the end of the 1st course of direct moxibustion, the contents of serum TSGF and TNF-α of rats in the prevention group 1 were significantly increased compared with that of the model group (P<0.05). At the end of the 2nd course of direct moxibustion, serum TSGF and TNF-α levels of rats in the model group were higher than the normal group with significantly difference (P<0.05), and the levels of TSGF and TNF-α in the prevention group 2 were significantly reduced in comparison with the model group (P<0.05)., Conclusion: It was possible that direct moxibustion could inhibit precancerous lesion and postpone hepatocarcinogenesis, and the therapeutic effect of two courses were better than one course.

This study investigated the impacts of four cultivation patterns including farmer practice, high yield and high efficiency practice, super high yield practice, and super high yield and high efficiency practice on yields, soil nitrate and nitrogen (N) balances in 3 winter wheat-summer maize rotations with straw returning in Hebei Province. Results showed that the super high yield practice was identified with greatest winter wheat and summer maize yields, followed by high yield and high efficiency practice, and super high yield and high efficiency practice, which were all greater than that of farmer practice. The N use efficiency of high yield and high efficiency practice was significantly greater than the other cultivation patterns. The total nitrate accumulation in 0-400 cm soil of these cultivation patterns reached 768.4-1133.3 kg·hm -2 , where 80%-85% of the accumulated nitrate were in 90-400 cm soil. Meanwhile, the nitrate leaching was observed in all cultivation patterns and nitrate accumulation peaks at 120-150 cm and 270-330 cm were found. Soil nitrate content of high yield and high efficiency practice was less than 30 mg·kg -1 and generally lower than other cultivation patterns, which to some extent reduced the environmental risk. In addition, nitrate surplus in 0-90 cm soil during winter wheat season was lower than that during summer maize season, and the high yield and high efficiency practice had the lowest apparent nitrogen loss. Overall, the high yield and high efficiency practice was evaluated to be the best cultivation pattern in consi-deration of yield, nitrogen use efficiency and nitrate accumulation in soil, but there was still certain achievable improvement potential.

Mastitis is the most important disease in the global dairy industry, and causes large economic losses. Staphylococcus aureus is one of most common pathogens that cause bovine mastitis. CXCR1 has been implicated as a prospective genetic marker for mastitis resistance in dairy cows; CXCR1 expression significantly increases when cows have mastitis. To investigate the mechanisms involved in its increased expression, bisulfite sequencing polymerase chain reaction (PCR) was used to detect the methylation status of CXCR1 CpG island, and quantitative fluorescence PCR was used to detect CXCR1 expression in bovine mammary tissue induced with S. aureus in three Chinese Holstein cows. No CpG island was found for bovine CXCR1 in the upstream 2-kb region, whereas one CpG island that contained 13 CpG sites was found in exon 1 of CXCR1. All of the CpG sites were under hypermethylation from 90 to 100% in the mammary tissues. When the mammary gland mRNA expression of CXCR1 was 12.10-fold higher in infected cow quarters than in uninfected quarters, the methylation levels of the CpG site at position 519 were significantly lower in the infected quarters than in the uninfected quarters. Pearson correlation analysis showed that the methylation level at position 519 was significantly negatively correlated with the CXCR1 mRNA expression level (P < 0.05). These results indicate that the methylation of the CpG site at position 519 may regulate CXCR1 expression in cows with mastitis induced by S. aureus, but further studies are needed to elucidate the mechanisms involved.

Previous studies have identified 8q24 as an important region to prostate cancer (PCa) susceptibility. The aim of this study was to investigate the role of six genetic variants on 8q24 (rs1447295, A; rs6983267, G; rs6983561, C; rs7837688, T; rs10090154, T and rs16901979, A) on PCa risk in Chinese population. Online electronic databases were searched to retrieve related articles concerning the association between 8q24 variants and PCa risk in men of Chinese population published between 2000 and 2014. Odds ratio (ORs) with its 95% correspondence interval (CI) were employed to assess the strength of association. Total eleven case-control studies were screened out, including 2624 PCa patients and 2438 healthy controls. Our results showed that three risk alleles of rs1447295 A (OR=1.35, 95% CI=1.19-1.53, P<0.00001), rs6983561 C (C vs. A: OR=1.41, 95% CI=1.21-1.63, P<0.00001) and rs10090154 T (T vs. C: OR=1.48, 95% CI=1.22-1.80, P<0.00001) on8q24 were significantly associated with PCa risk in Chinese population. Furthermore, genotypes of rs1447295, AA+AC; rs6983561, CC+AC and CC; rs10090154, TT+TC; and rs16901979, AA were associated with PCa as well (P<0.01). No association was found between rs6983267, rs7837688 and PCa risk. In conclusions, variants including rs1447295, rs6983561, rs10090154 and rs16901979 on 8q24 might be associated with PCa risk in Chinese population, indicating these four variations may contribute risk to this disease. This meta-analysis was the first study to assess the role of 8q24 variants on PCa risk in Chinese population.

Aim: To investigate the roles and interactions of rho-associated protein kinase (ROCK)1 and miR-124 in human colorectal cancer (CRC)., Methods: Expression of ROCK1 protein was examined by Western blotting, and quantitative reverse transcriptase PCR was performed to measure expression of ROCK1 mRNA and miR-124. Two cancer cell lines were transfected with pre-miR-124 (mimic) and anti-miR-124 (inhibitor) and the effects on ROCK1 protein and mRNA expression were observed. In addition, cell proliferation was assessed via a 5-ethynyl-2' deoxyuridine assay. Soft agar formation assay, and cell migration and invasion assays were used to determine the effect of survivin on the transformation and invasion activity of CRC cells., Results: miR-124 was significantly downregulated in CRC compared to normal specimens (0.603 ± 0.092 vs 1.147 ± 0.286, P = 0.016) and in metastatic compared to nonmetastatic CRC specimens (0.416 ± 0.047 vs 0.696 ± 0.089, P = 0.020). Expression of miR-124 was significantly associated with CRC metastasis, tumor T and N stages, and tumor grade (all P < 0.05). ROCK1 protein was significantly increased in CRC compared to normal tissues (1.896 ± 0.258 vs 0.866 ± 0.136, P = 0.026), whereas ROCK1 mRNA expression was unaltered (2.613 ± 0.251 vs 2.325 ± 0.246). miR-124 and ROCK1 were inversely expressed in CRC tissues and cell lines. ROCK1 mRNA was unaltered in cells transfected with miR-124 mimic and miR-124 inhibitor, compared to normal controls. There was a significant reduction in ROCK1 protein in cells transfected with miR-124 mimic and a significant increase in cells transfected with miR-124 inhibitor (Ps < 0.05). Transformation and invasion of cells transfected with miR-124 inhibitor were significantly increased compared to those in normal controls (P < 0.05). Cells transfected with miR-124 inhibitor showed increased cell proliferation., Conclusion: miR-124 promotes hyperplasia and contributes to invasion of CRC cells, but downregulates ROCK1. ROCK1 and miR-124 may play important roles in CRC.

In our previous paper, we analyzed "Deqi" in book Huangdi Neijing (The Yellow Emperor's Internal Classic) and Nanjing (Canon of Difficult Medical Problems) from "Zhishen"(Treating mentality) and Tiaoqi (Regulating qi). In the present paper, the authors discuss the connotations of "Deqi" and related events in the later ages of the abovementioned two classic books to the later stage of the Qing Dynasty when involves about 20 classical works as Zhenjiu Dacheng ( The Great Compendium of Acupuncture and Moxibustion), Zhenjing Zhinan (Guide to the classics of Acupuncture), Zhenjiu Daquan (A Complete Works of Acupuncture and Moxibustion) etc. from 1) close association between "Deqi" and patients' mental activity; 2) how to wait for arrival of qi if the needling does not induce "Deqi" for the time being; 3) how to identify "qi-arrival" and then, performing suitable manipulations; 4) Deqi and shallow- or deep-needling; 5) putting more emphasis on patients' feeling and reactions, rather than the practitioners perception beneath the needle which is described in book Huangdi Neijing; and 6) not withdrawing the acupuncture needles if qi does not arrive. Generally, in the later ages, the connotations of Deqi are enriched greatly.

A search on acupuncture Deqi was conducted using four Chinese-language biomedical databases (CNKI, Wan-Fang, VIP and CBM) and PubMed database and using keywords "Deqi" or "needle sensation" "needling feeling" "needle feel" "obtaining qi", etc. Then, a "Modern Literature Database for Acupuncture Deqi" was established by employing Microsoft SQL Server 2005 Express Edition, introducing the contents, data types, information structure and logic constraint of the system table fields. From this Database, detailed inquiries about general information of clinical trials, acupuncturists' experience, ancient medical works, comprehensive literature, etc. can be obtained. The present databank lays a foundation for subsequent evaluation of literature quality about Deqi and data mining of undetected Deqi knowledge.

Background: The nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. However, the influence of visceral nerve (VN) on acute necrotizing pancreatitis (ANP) has drawn little attention., Aim: To investigate the influence of VN on the pathophysiological process of ANP in dogs., Methods: The dogs were divided into a sham operation (SO) group, ANP group, ANP + vagal nerve trunk transection (VNTT) group, and ANP + greater splanchnic nerve transection (GSNT) group. The VNTT and GSNT groups underwent VNTT and GSNT respectively immediately after ANP induction. The levels of serum pancreatic amylase (AMY), calcium, high-sensitivity C-reactive protein (HCRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-10 (IL-10) were monitored dynamically and the pathological examinations of the pancreas was performed at postoperative day 7., Results: All serum parameters among the four groups showed no differences before the experiment (p > 0.05). At different postoperative times, the serum TNF-α, IL-1β, HCRP, and AMY were significantly increased, however, the serum calcium and IL-10 had dropped in the ANP group versus SO group (p < 0.05); an alike variation trend occurred between the VNTT group and ANP group (p < 0.05); an opposite variation trend occurred between the GSNT group and the ANP group (p < 0.05). The pancreas pathological scoring of VNTT group was highest in the four groups (p < 0.05) and GSNT group was lower versus ANP group (p < 0.05)., Conclusions: The GSNT has been shown to alleviate development of ANP, however, VNTT may exacerbate the ANP.

Aim: To investigate the expression of microRNA-218 (miR-218) in serum from gastric cancer patients and its relationship with clinicopathological characteristics., Methods: A total of 68 patients with pathologically diagnosed gastric cancer and 56 healthy individuals were recruited to this study. The expression of miR-218 was detected in the serum of gastric cancer patients and healthy individuals by quantitative real-time polymerase chain reaction. The clinical data were collected and analyzed by statistical software., Results: miR-218 was reduced significantly in the serum of gastric cancer patients compared to healthy individuals (1.15 ± 0.08 vs 0.37 ± 0.023; P = 0.026). In the gastric cancer group, serum expression of miR-218 was lower in patients with metastasis and poorly differentiated cancer compared with non-metastatic and well-differentiated cancer (0.19 ± 0.011 vs 0.45 ± 0.021, P = 0.031 and 0.21 ± 0.019 vs 0.49 ± 0.021, P = 0.025). Serum miR-218 was found to be significantly associated with gastric cancer metastasis (P = 0.003), tumor T stage (P = 0.018) and tumor grade (P = 0.012). Low serum expression of miR-218 was related to an increase in the stage of gastric cancer. The expression level of miR-218 in the serum was correlated with the 3-year survival. Ninety-seven percent of patients with a high level of miR-218 expression survived for 3 years, while only 54% of those with low miR-218 expression survived., Conclusion: miR-218 is deregulated in gastric cancer patients and is strongly correlated with tumor stage, grade and metastasis. Serum expression of miR-218 may be a prognostic marker.

Acupuncturists have always paid high attention to deqi (needling sensation) in clinical. However, relationship between deqi and curative effect has not been elucidated yet. In order to have a further understanding on effect of deqi on clinical effect, through study on literature associated with deqi since the establishment of People's Republic of China in 1949, it is held that various factors can influence therapeutic effect of acupuncture treatment, including whether needling sensation appears or not, the speed of deqi, the intensity of deqi, different types of sensations as well as propagated sensation along meridians (PSM). Joint launched multidisciplinary researches should be carried out to reveal the influence principle of deqi on acupuncture effect, and to lay foundations for the further studies on mechanism of deqi.

Objective: To evaluate the efficacy and safety of the combination therapy of tamsulosin and solifenacin for mild and moderate benign prostatic hyperplasia (BPH) with overactive bladder (OAB)., Methods: We randomly divided 166 patients with BPH and concomitant OAB into a mild obstruction symptom group (n = 88) and a moderate obstruction symptom group (n =78), 48 of the former group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 40 with 0. 2 mg tamsulosin; 36 of the latter group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 42 with 0. 2 mg tamsulosin, all administered once daily for 12 weeks. We obtained the International Prostate Symptom Score (IPSS), urine storage period symptom score (USPSS), voiding symptom score (VSS), Qmax, residual urine volume, OAB symptom score (OABSS) and adverse reactions, and compared them among different, Results: Among the patients with mild obstruction symptoms, the combination of tamsulosin and solifenacin achieved remark-groups. able improvement in IPSS, USPSS, Qmax and OABSS as compared with the baseline (P < 0.05), but made no significant difference in the residual urine volume (P > 0. 05) , while tamsulosin improved IPSS only (P < 0.05). The combination therapy exhibited an obvious superiority over tamsulosin alone in improving IPSS (9.7 micro 3.0 vs 15.8 micro 3.3), USPSS (8. 1 micro 1.7 vs 12.3 micro 3.1), Qmax ([18.6 micro 2.3] ml/s vs [14.2 micro 2.3] ml/s ), and OABSS (5.3micro 1.3 vs 9.7 micro 2.7) (P < 0.05), but there were no obvious differences in residual urine, urine routine test results and adverse events between the two therapies ( P > 0. 05). In those with moderate obstruction symptoms, the combination therapy significantly improved IPSS, VSS, Qmax and OABSS (P < 0.05) but not the residual urine (P > 0. 05) in comparison with the baseline. The tamsulosin therapy achieved obvious improvement in IPSS, VSS, Qmax, OABSS and residual urine. The combination therapy showed a better effect than tamsulosin only in OABSS (4. 8 +/-1.5 vs 6.5 +/-2.5, P < 0.05), but no significant differences from the latter in IPSS, Qmax, VSS, routine urine test results, and adverse, Conclusion: Combination therapy of tamsulosin and solifenacin is obviously safe and efficacious in the treatment (P > 0.05). events of both mild and moderate BPH with concomitant OAB, and it is superior to tamsulosin alone.

Taking Doctor HUANG Shi-ping as the representative, the school of Huang's golden needle is based on Chinese martial art. Golden needles are adopted as main tool. Attaching great importance on the combination of acupuncture and moxibustioin, it is also characterized with penetrating needling with long needles. Through the development of three generations, it once outshone other schools in the field of acupuncture, and became famous all over the world. It made great contribution to the development of the course of acupuncture. However, with the development of the history, the form of acupuncture education as well as apparatus were all undergone an unified reform. Therefore, Doctor HUANG Shi-ping's acupuncture school be lost gradually.

After searching for literature about the specificity of acupoints from China National Knowledge Infrastructure (CNKI) database (in Chinese) and MEDLINE (in English), published by Chinese scholars from June 2003 to June 2012, the authors made a systemic analysis on the retrieved papers. It was found that most Chinese scholars took a positive viewpoint about the specificity of acupoints in morphological structure, biophysical characters, pathological reactions, acupuncture stimulation-induced responses in different brain regions and therapeutic effects. However, the research methods and comprehensive analysis of abundant research results need being improved, and the conclusion should be validated extensively. Moreover, the research on the affecting factors of specificity of acupoints will be one of the major directions.

Objective: To systematically assess the effects of neoadjuvant chemotherapy on the prognostic risk of invasive transitional bladder cancer., Methods: All known randomized controlled trials (RCTs) on neoadjuvant chemotherapy in the treatment of invasive transitional bladder cancer, published from the date of database building to September 2012, were retrieved from such databanks as Pubmed, CBMdisc, Embase and Cochrane. The data on 5-year survival rate of included studies were extracted for further heterogeneity exploration, subgroup analysis and statistical pooling with the RevMan 5.10 software., Results: Fourteen subjects involving 2072 cases and 2086 controls were published from 1991 to 2012. The overall odds ratio of survival suggested a 21% relative reduction in mortality risk for neoadjuvant chemotherapy compared to that on control (OR = 0.79, 95%CI:0.70-0.90). In subgroup analysis according to different neoadjuvant chemotherapies, MCV (methotrexate, cisplatin and vinblastine) and MVAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapies showed significant benefit to overall survival with 28% and 25% reduction in risk of death respectively (OR = 0.72,95%CI:0.60-0.86, OR = 0.75,95%CI:0.59-0.96) . However, no significant difference existed in effects between C (cisplatin) chemotherapy, CM (cisplatin and methotrexate) chemotherapy and CD (cisplatin and docetaxel) chemotherapy and controls. In subgroup analysis according to local treatment of cystectomy or radiotherapy after neoadjuvant chemotherapy, the patients with cystectomy showed significant benefits in overall survival with 25% reduction in risk of death (OR = 0.75, 95%CI:0.65-0.87). However, the patients with radiotherapy or radiotherapy plus cystectomy showed no significant benefits in overall survival., Conclusions: MCV and MVAC neoadjuvant chemotherapies improve survival among patients with bladder cancer. And neoadjuvant chemotherapy has better long-term survival after cystectomy.

With retrieval in CNKI and MEDLINE data base, the articles in Chinese and English that were written by Chinese authors, which were about the specificity of acupoint effects during "the Eleventh Five-Year (2006-2010)", are included. Researchers have studied about the specificity of acupoint effects by cerebral function imaging technique and it turns out that from the perspective of central mechanism, there are differences among aupoint stimulatory effect. The curative effect of acupoints is significantly better than that of nonacupoints, different acupoints have different curative effects, the effect of disease-related acupoints is better than that of unrelated acupoints, those above have intitally proved the existence of specificity of acupoint effects. However, part of the research results need futher summaries, analysis and promotion as well as try to avoid low-level repeat in research design.

: Vascular endothelial cells (ECs) line the luminal surface of blood vessels, which are exposed constantly to mechanical stimuli, such as fluid shear stress, cyclic strain, and blood pressure. In recent years, more and more evidence indicates that ECs sense these mechanical stimuli and subsequently convert mechanical stimuli into intracellular signals. The properties of ECs that sense the mechanical stimuli are defined as mechanosensors. There are a variety of mechanosensors that have been identified in ECs. These mechanosensors play an important role in regulating the function of the endothelium and vascular function, including blood pressure. This review focuses on the mechanosensors that have been identified in ECs and on the roles that mechanosensors play in the regulation of endothelium function, and in the regulation of vascular function.

Objective: To discuss the influence of factors related organic on deqi in acupuncture treatment and provide scientific evidence for further research on the influencing factors of deqi sensation., Methods: China National Knowledge Infrastructure (CNKI) database, VIP-Chinese scientific and technological journal database, Chinese biological medical (CBM) database and PubMed database were retrieved. There were 30 articles about the organic influencing factors of deqi and they were analyzed., Results: The organic related factors which includes individual constitution, syndrome classification, physical condition, specificity of acupoint function, tolerance and psychological factors play an important part in deqi in acupancture treatment, which should be brought to the forefront for acupuncture practitioners and researchers., Conclusion: The organic factors are influencing the deqi sensation in many ways but most of the present studies are resting on the affirmation of the phenomenon. Further studies about organic related influencing factors on deqi should be carried out and scientific, objective indices of deqi sensation should be explored which may improve the clinical and research level of acupuncture.

Unlabelled: Deqi (needle sensation), is closely related to clinical therapeutic effect of acupuncture in the treatment of different clinical conditions. In the present paper, the authors summarized various components or concepts of Deqi mainly in the foreign studies collected from Pubmed database. At present, foreign researches about Deqi mainly include 1) the subjects' subjective qualitative and quantitative descriptions about Deqi, 2) correlation between acupuncture stimulation induced Deqi and clinical therapeutic effects, and 3) responses of different brain regions or the connectivity of brain network shown by functional magnetic resonance imaging (fMRI) during Deqi by needling different acupoints. According to the current commonly used 6 questionnaires, aching, tingling, numbness, heaviness, dull pain, throbbing, and deep pressure sensation are the most frequently seen components of Deqi of acupuncture stimulation. The factors influencing Deqi are psychological state, personal previous experience and cultural background. Regarding the degree of Deqi and clinical effects or outcomes, the conclusions are controversial., Results: of fMRI analysis shows that in spite of extensive deactivation of the limbic system has been found in many studies, and the connectivity of the intrinsic brain functional networks is increased during acupuncture-induced Deqi, the significance of activation or deactivation of some brain regions remains unclear, and the related mechanisms need to be studied further. No matter activation or deactivation of different brain regions during Deqi, the most important issue is the relationship between Deqi and clinical therapeutic effects. Further studies are definitely needed.

Objective: To observe the influence of electroacupuncture (EA) stimulation of "Hegu" (LI 4) and "Sanyinjiao"(SP 6; a classical delivery-facilitating acupoint recipe) at different parameters on endocrine hormone levels of late-stage pregnant rats, so as to find the better stimulation parameters for delivery facilitation., Methods: Ninety-six female Wistar rats were randomly divided into eight groups: normal control (normal), pregnancy (model), EA-15 Hz, EA-30 Hz, EA-50 Hz, EA-2 Hz/ 15 Hz, EA-2 Hz/30 Hz and EA-2 Hz/50 Hz, with 12 rats in each group except EA-30 Hz group (n = 10). EA stimulation (0.2 to 0. 3 mA) was delivered to bilateral LI 4 for 20 min and then bilateral SP 6 for 5 min (25 min). The contents of serum estradiol (E2), progesterone (P) and prostaglandin E2 (PGE2) were detected by ELISA., Results: Compared with the normal group, serum E2, P and PGE2 contents were significantly increased in the pregnancy model group (P<0.01), and E2/ P level was downregulated mildly (P>0.05). Compared with the model group, the contents of serum E2 in the EA-15 Hz, EA-30 Hz, EA-50 Hz, EA-2 Hz/15 Hz and EA-2 Hz/50 Hz groups, serum PGE2 contents in the EA-15 Hz, EA-30 Hz and EA-2 Hz/50 Hz groups, and E2/P levels in the EA-15 Hz, EA-30 Hz, EA-50 Hz and EA-2 Hz/50 Hz groups were significantly increased (P<0.01, P<0.05), whereas serum P contents in the EA-15 Hz, EA-30 Hz, EA-50 Hz and EA-2 Hz/50 Hz groups were significantly down-regulated (P<0. 01, P<0. 05). The effects of EA-2 Hz/50 Hz group were significantly superior to those of EA-2 Hz/15 Hz and EA-2 Hz/ 30 Hz groups in raising serum E2 and E2/P levels (P<0.05, P<0.01). No significant differences were found among the EA-15 Hz, EA-30 Hz, EA-50 Hz and EA-2 Hz/50 Hz groups in raising serum E2, PGE2 and E2/P levels, and among the EA-30 Hz, EA-50 Hz and EA-2 Hz/50 Hz groups in lowering serum P levels (P>0. 05). It displayed that the effects of EA at 15 Hz, 30 Hz and 2 Hz/50 Hz on the abovementioned 4 indexes were relatively better., Conclusion: EA of LI 4 and SP 6 at 15 Hz, 30 Hz and 2 Hz/ 50 Hz can effectively up-regulate serum E2, PGE2 and E2/P levels and down-regulate serum P content in pregnancy rats, which may contribute to its effect in promoting labor.

With retrieval of MEDLINE database (from Jan 2006 to Dec 2010) and supplementary search on other important literatures, 29 overseas articles that were in accord with inclusive criteria were included. The results showed that the overseas scholars issued the international standard on human acupoint locations and proposed the localization system of animal acupoint model; discovered the new acupoint structure, characteristic of acupoint microcirculation, the states of the diseases could be specifically reflected through acupoint temperature, electric resistance, pressure and pain threshold, and the specific brainstem reaction could be induced by electroacupuncture at acupoints; verified initially the effect on nausea and vomiting with the related acupuncture methods at acupoints and explained the mechanisms on the local analgesia of acupuncture at acupoints; suggested that a further study should be expected on the low electric resistance property of acupoints and the effect specificity in the treatment of disease. Additionally, they were proposed that the domestic study should focus on the symptom treatment, correct application of logic reasoning, the secondary literature study and international exchange and cooperation. It is indicated that the overseas study has made the great progression on the acupoint locations, morphological structure, biological and physical properties, pathological reaction, stimulation effect, therapeutic effect and mechanism, and it provides the references for the domestic study in terms of study clues and methods.

Aims: To examine a novel strategy to enhance the survival of grafted neural stem cells (NSCs) in stroke model., Methods: Using a cell counting kit-8 (CCK-8) and TUNEL assay to test the protective effects of p53 inhibitor, pifithrin-α (PFT-α), on oxygen glucose deprivation (OGD) in NSCs. We compared the effects of vehicle + NSCs and FFT-α + NSCs on the efficacy of transplantation in stroke rat model using behavioral analysis, immunohistochemistry, etc., Results: Pifithrin-α increased viability and decreased apoptosis in NSCs after OGD in vitro. By in vivo studies, we showed that the best recovery of neurological function in the stroke rats and the maximum survival of grafted NSCs were found in the PFT-α + NSCs group. Twelve hours after cell transplantation, p53 was localized to the nuclei of grafted NSCs in the vehicle + NSCs group but was primarily localized to the cytoplasm in the PFT-α + NSCs group. The p53-upregulated modulator of apoptosis (PUMA) was highly expressed among the grafted cells in the vehicle + NSCs group compared with that in the PFT-α + NSCs group., Conclusion: Our results indicate that PFT-α enhances the survival of grafted NSCs through the inhibition of p53 translocation into the nucleus., (© 2012 Blackwell Publishing Ltd.)

Deqi sensation is believed to be important in clinical efficacy according to TCM theory. The measuring method of Deqi sensation has significant implications for the result of research trials. This study makes an investigation on acupuncture-experienced patients and expert acupuncturists in China and aims to find out the patient's needling sensations and acupuncturist's sensations which can be acceptable as descriptors of Deqi sensation, so as to provide foundation for more systematic and sensitive quantitative evaluation method of Deqi sensation. Results of this survey indicated that the Deqi sensation noted by both patient and acupuncturist is equally important to the treatment efficacy. It is found that there are some differences between the patients' real-life experience and the acupuncturists' expectations on patients' Deqi sensation. The "dull pain," "aching," "sore," "numb," "distended," "heavy," "electric," "throbbing," "warmness," "coolness," "spreading," and "radiating" can be considered as the main manifestations of Deqi sensations. The acupuncturists believed that Deqi sensations were mainly "pulling," "tight," and "throbbing." We suggest developing a questionnaire measuring the Deqi sensations which includes both the sensations of the patient and acupuncturist, and this would be very important and necessary for a better understanding of the relationship between Deqi sensation and acupuncture effects in future studies.

Through CNKI retrieval, 40 articles were selected from Medical Journals published between January 2003 and December 2011, and the study designs, intervention methods and conclusions of the articles were analyzed. It turned out that in the area of clinical research, the main usage of acupuncture was assist treatment of artificial abortion and drug-induced abortion: in artificial abortion, acupuncture can play a role in analgesia, artificial abortion syndrome relieving, and cervix dilating, while in the drug induced abortion, acupuncture can play a role in improving completed abortion rate, accelerating foetal sac release, decreasing side effects and regulating postoperative bleeding. In mechanism research, the effect of acupuncture on uterine tissue was revealed in terms of neuroendocrine. Although the certain role of acupuncture in assisting artificial abortion and drug-induced abortion has been confirmed in numerous clinical trials, its mechanism revealing was limited. The further study should focus on improving research method, acupuncture manipulation standardization and stimulation parameters optimization. What's more, the revealing of acupuncture's role in anti-early pregnancy should be emphasized to improve its effectiveness and scientificalness.