Mechanism of Acupuncture in Treating Obesity: Advances and Prospects.

Obesity is a common metabolic syndrome that causes a significant burden on individuals and society. Conventional therapies include lifestyle interventions, bariatric surgery, and pharmacological therapies, which are not effective and have a high risk of adverse events. Acupuncture is an effective alternative for obesity, it modulates the hypothalamus, sympathetic activity and parasympathetic activity, obesity-related hormones (leptin, ghrelin, insulin, and CCK), the brain-gut axis, inflammatory status, adipose tissue browning, muscle blood flow, hypoxia, and reactive oxygen species (ROS) to influence metabolism, eating behavior, motivation, cognition, and the reward system. However, hypothalamic regulation by acupuncture should be further demonstrated in human studies using novel techniques, such as functional MRI (fMRI), positron emission tomography (PET), electroencephalogram (EEG), and magnetoencephalography (MEG). Moreover, a longer follow-up phase of clinical trials is required to detect the long-term effects of acupuncture. Also, future studies should investigate the optimal acupuncture therapeutic option for obesity. This review aims to consolidate the recent improvements in the mechanism of acupuncture for obesity as well as discuss the future research prospects and potential of acupuncture for obesity.

Pectic polysaccharides ameliorate the pathology of ulcerative colitis in mice by reducing pyroptosis.

Background: Ulcerative colitis (UC) is an inflammatory bowel disease which seriously affects the quality of life of patients. There has been an increasing amount of research related to the therapeutic effects and mechanisms of natural plant substances in the treatment of recurrent UC. Rauwolfia verticillata var. Hainanensis is a medicinal plant that is native to Hainan Island, China. Some studies have documented that pectic polysaccharides (PPs) from Rauvolfia inhibited the progression of colon ulcers. However, their mechanisms of action have not been established. Studies have revealed that suppressing pyroptosis can attenuate the damage of experimental colitis. However, it is unclear whether PPs from Rauvolfia verticillata inhibit inflammation through pyroptosis. This study investigated the effects and potential mechanisms of PPs extracted from Rauvolfia verticillata on experimental UC in mice. Methods: Male C57 mice (6-8 weeks old) were allocated into the control group, the dextran sulfate sodium (DSS)-induced UC model group (DSS group), or the DSS with pectic polysaccharides treatment group (DSS + PP group). The body weights, rectal bleeding, and stool consistencies in the mice were observed, and the disease activity index (DAI) score was calculated. Colon tissues were collected for pathological analysis by histological hematoxylin and eosin (H&E) staining. The levels of caspase-1 and interleukin (IL)-1ß were detected by immunohistochemistry. Pyroptosis was assessed by transmission electron microscopy. Results: UC in mice induced by DSS resulted in decreased general physical activity and body weight, increased DAI score, significant histological changes, inhibited caspase-1 and IL-1ß expression, and promoted pyroptosis. These DSS-induced changes could be partially ameliorated by administration of PP. Conclusions: PPs exerted an ameliorative effect on DSS-induced UC in mice by reducing pyroptosis.

Astragalus Polysaccharides Reduce High-glucose-induced Rat Aortic Endothelial Cell Senescence and Inflammasome Activation by Modulating the Mitochondrial Na+/Ca2+ Exchanger.

Vascular endothelial cells play a vital role in atherosclerotic changes and the progression of cardiovascular disease in older adults. Previous studies have indicated that Astragalus polysaccharides (APS), a main active component of the traditional Chinese medicine Astragalus, protect mitochondria and exert an antiaging effect in the mouse liver and brain. However, the effect of APS on rat aortic endothelial cell (RAEC) senescence and its underlying mechanism have not been investigated. In this study, we extracted RAECs from 2-month-old male Wistar rats by the tissue explant method and found that APS ameliorated the high-glucose-induced increase in the frequency of SA-ß-Gal positivity and the levels of the senescence-related proteins p16, p21, and p53. APS increased the tube formation capacity of RAECs under high-glucose conditions. Moreover, APS enhanced the expression of the mitochondrial Na+/Ca2+ exchanger NCLX, and knockdown of NCLX by small interfering RNA (siRNA) transfection suppressed the antiaging effect of APS under high-glucose conditions. Additionally, APS ameliorated RAEC mitochondrial dysfunction, including increasing ATP production, cytochrome C oxidase activity and the oxygen consumption rate (OCR), and inhibited high-glucose-induced NLRP3 inflammasome activation and IL-1ß release, which were reversed by siNCLX. These results indicate that APS reduces high-glucose-induced inflammasome activation and ameliorates mitochondrial dysfunction and senescence in RAECs by modulating NCLX. Additionally, APS enhanced the levels of autophagy-related proteins (LC3B-II/I, Atg7) and increased the quantity of autophagic vacuoles under high-glucose conditions. Therefore, these data demonstrate that APS may reduce vascular endothelial cell inflammation and senescence through NCLX.

Rauwolfia vomitoria Extract Represses Colorectal Cancer Cell Autophagy and Promotes Apoptosis.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequent digestive tract tumors in the world with an increasing incidence. Currently, surgical resection and chemotherapy are the main therapeutic options; however, their effects are limited by various adverse reactions. Rauwolfia vomitoria extract (Rau) has been shown to repress the progression of multiple human cancers; however, whether Rau plays a role in CRC remains undetermined. METHODS: Influences of Rau treatment on HCT-116 and LoVo cells were estimated via MTT and colony formation experiments. Flow cytometry analysis was adopted to evaluate the apoptosis rate of HCT-116 and LoVo cells. Apoptosis-related proteins (Bcl-2, Bax, and caspase-3) and autophagy-related proteins (LC3 and P62) were assessed by Western blotting. Effects of Rau on autophagy of HCT-116 and LoVo cell were evaluated through GFP-LC3 analysis. In vivo xenograft tumor assay was conducted to further examine the role of Rau in CRC tumor growth. RESULTS: Rau remarkably repressed HCT-116 and LoVo cell viability and promoted HCT-116 and LoVo cell apoptosis in vitro in a dose-dependent manner. Rau increased the expression of caspase-3 and Bax and decreased the expression of Bcl-2 in HCT-116 and LoVo cells. Moreover, Rau was demonstrated to decrease the LC3||/LC3| ratio and increase the level of P62 in HCT-116 and LoVo cells. In addition, we found that Rau repressed xenograft tumor growth and also repressed autophagy in vivo. CONCLUSION: Our findings revealed that Rau repressed CRC cell viability and autophagy in vitro and in vivo, suggesting that Rau might be a potent therapeutic agent of CRC.

Towards Holistic Governance of China's E-Waste Recycling: Evolution of Networked Policies.

Electronic products are being updated and replaced much faster and there is therefore an increasing growth in electronic waste (e-waste). In order to promote professional recycling of e-waste, the relevant government departments of China have published a series of policies. This paper aims to unearth the evolution tendency of the networked policies towards holistic governance of China's e-waste recycling. Content analysis, quantitative text analysis and network analysis are applied to analyze relevant policy documents from 2001 to 2016. This paper illustrates evolution of policy themes, evolution of intergovernmental relationships, and evolution of policy relations. This study reveals policy intentions, maps policy progress, and unearths governance philosophy, providing an overall understanding of the policy ways by which the Chinese government has deployed its guiding strategies on professional recycling of e-waste. This paper illustrates how to approach holistic governance from perspective of networked policies, contributing to answering the central question of holistic governance about how to achieve it.

[Start-up and Optimization of Denitrifying Phosphorus Removal in ABR-MBR Coupling Process].

The feasibility of the denitrifying phosphorus removal process in the ABR-MBR system with no sludge reflux and high concentration of seeding activated sludge (25 g ·L-1, in MLSS) in the ABR was investigated. The characteristics of the microbial community in the denitrifying phosphorus removal compartment were also evaluated. The denitrifying phosphorus removal function was achieved by gradually increasing the reflux ratio (R) from 0% to 200%. During the stable operation, the average removal rates of COD, PO43--P, and TN in the system were 88.28%, 54.45%, and 61.93%, respectively. When the influent loading rate, NOx--N reflux ratio, and hydraulic retention time (HRT) of ABR and MBR were 0.8 kg ·(m3 ·d)-1, 150%, and 9 h and 3.3 h, respectively, the average VFA concentration of 80.58 mg ·L-1, ρ(NO2--N)/ρ(NO3--N) reflux ratio of 1.68, and PO43--P and TN removal rates of 64.94% and 62.95% were obtained. The short-cut nitrification denitrifying phosphorus removal was achieved in the ABR-MBR system. Batch tests showed that denitrifying phosphorus removal bacteria (DPAOs) were the main functional bacteria in the ABR, with anaerobic phosphorus release and anoxic phosphorus uptake of 3.73 mg ·L-1 and 10.22 mg ·L-1, respectively. High throughput sequencing results showed that Proteobacteria and Bacteroidetes were the dominant phyla in the phosphorus removal compartment, accounting for 23.49%-53.66% and 16.55%-21.78% of the total phyla, respectively. Thauera, Thiothrix, Pseudomonas, norank_ f_Rhodocyclaceae, and unclassification_ f_Rhodocyclaceae in Proteobacteria, and Sphingobacteriales in Bacteroidetes were the potential denitrifying phosphorus removal microorganisms.

Nano-lanthanum hydroxide, a novel phosphate binder, for treating hyperphosphatemia: A preclinical study.

This study is to determine the pharmacological effects of nano-lanthanum hydroxide (nano-LH) in the treatment of hyperphosphatemia, in comparison with other phosphate binders. Rat models of chronic renal failure and hyperphosphatemia were induced by adenine, which were treated with nano-LH (0.15, 0.10, and 0.05 g/Kg/d), lanthanum carbonate (0.30 g/Kg/d), and normal-size lanthanum hydroxide (0.10 g/Kg/d), respectively. To investigate the therapeutic effects, the serum levels of phosphorus, Scr, Ucr, BUN, UUN, PTH, and other hyperphosphatemia-related biochemical indicators were determined. A novel phosphorus-binding agent, nano-LH, was synthesized herein, which was rod-like particle with the length of 30-50 nm, width of 10-20 nm, and diameter of 5-10 nm. In vitro phosphorus binding experiments showed that nano-LH had better binding rate. Pharmacodynamic experiments confirmed that the therapeutic effects of lanthanum-hydroxide (0.10 g/kg/d) were superior to other existing phosphate binders in rat models of hyperphosphatemia, in lowering the blood phosphate level and improving the renal function. In the term of drug safety, our preliminary results showed that the nano-LH at appropriate dose did not cause death cases in mice, and the serum levels of alkaline phosphatase and lactate dehydrogenase were not significantly changed, indicating good oral safety. Nano-LH has high potency compared with several phosphate binders, which might be a promising therapeutic agent for the treatment of hyperphosphatemia in clinic.

Pectic polysaccharides extracted from Rauvolfia verticillata (Lour.) Baill. var. hainanensis Tsiang ameliorate ulcerative colitis via regulating the MAPKs and NF-κB pathways in dendritic cells.

This study was to investigate the effects and mechanisms of pectic polysaccharides (PP) extracted from Rauvolfia verticillata (Lour.) Baill. var. hainanensis Tsiang on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC). Eighty female BALB/c mice were randomly divided into four groups: Control, DSS, DSS + salicylazosulfapyridine (SASP), and DSS+ PP. The disease activity index (DAI), overall physical activity, and blood stool were monitored daily to evaluate severity of UC. Histological scores of the colon were observed. The expression of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPKs) pathways in colon tissues and bone marrow-derived dendritic cells (DCs) was assessed by western blot, immunohistochemistry, electrophoretic mobility shift assay (EMSA) and real time polymerase chain reaction (RT-PCR). Cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The overall physical activity, DAI and histological scores decreased in DSS+SASP and DSS+PP groups, compared with the DSS-alone group. Also, tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) reduced significantly while the expression of IκBα was up-regulated, extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 were activated, in DSS+SASP and DSS+PP groups. PP inhibited activation of MAPKs and NF-κB pathways in the bone-marrow-derived DCs. In conclusion, PP significantly ameliorated murine DSS-induced UC model, via regulation of MAPKs and NF-κB pathways in DCs.

The mechanism of iron-compensation for manganese deficiency of Streptococcus pneumoniae.

Given their involvement in catalysis, infection, and biofilm formation, Fe and Mn are essential for bacterial survival and virulence. In this study, we found that Streptococcus pneumoniae (S. pneumoniae) could grow in the Mn-deficient medium (MDCM). Furthermore, findings showed that the Fe concentration in the bacterium increased when the Mn concentration decreased. In addition, it was noted that supplementing MDCM with Fe resulted in the recovery of bacterial growth. Quantitative proteomics using stable-isotope dimethyl labeling was performed to investigate the adaptive growth mechanism of S. pneumoniae under Mn-deficient conditions. It was found that the expression levels of 25 proteins were downregulated, whereas those of 54 proteins were upregulated in S. pneumoniae grown in MDCM. It was also noted that several of the downregulated proteins were involved in cell energy metabolism, amino acid synthesis, and reduction of oxidation products. More importantly, several ATP-binding cassette transporters related to Fe uptake, such as PiuA, PiaA, PitA, and SPD_1609, were overexpressed for increased Fe uptake from the MDCM. The results suggest that Mn deficiency disturbs multiple metabolic processes in S. pneumoniae. Furthermore, it causes a compensatory effect of Fe for Mn, which is beneficial for the survival of the bacterium in extreme environments. SIGNIFICANCE: The relationship between manganese and iron metabolism in S. pneumoniae has not been clearly revealed. In this paper, we suggest that Mn limitation disturbs multiple metabolic processes and evidently decreases the ATP level in the bacterium. In order to survive in this extreme environment, bacteria upregulated three type of Fe ion transporters PiuABC (heme), PiaABC (ferrichrome) and PitABC (Fe3+) to uptake enough Fe ions to response to Mn deficiency. Therefore, this study reveals a bacterial mechanism of Fe compensation for Mn, and provides new insight for investigating the relativeness of Fe and Mn metabolism of bacteria.

Silicon Nanowire Field Effect Transistor Sensors with Minimal Sensor-to-Sensor Variations and Enhanced Sensing Characteristics.

Silicon nanowire field effect transistor (FET) sensors have demonstrated their ability for rapid and label-free detection of proteins, nucleotide sequences, and viruses at ultralow concentrations with the potential to be a transformative diagnostic technology. Their nanoscale size gives them their ultralow detection ability but also makes their fabrication challenging with large sensor-to-sensor variations, thus limiting their commercial applications. In this work, a combined approach of nanofabrication, device simulation, materials, and electrical characterization is applied toward identifying and improving fabrication steps that induce sensor-to-sensor variations. An enhanced complementary metal-oxide-semiconductor-compatible process for fabricating silicon nanowire FET sensors on 8 in. silicon-on-insulator wafers is demonstrated. The fabricated nanowire (30 nm width) FETs with solution gates have a Nernst limit subthreshold swing (SS) of 60 ± 1 mV/decade with ∼1.7% variations, whereas literature values for SS are ≥80 mV/decade with larger (>10 times) variations. Also, their threshold voltage variations are significantly (∼3 times) reduced, compared to literature values. Furthermore, these improved FETs have significantly reduced drain current hysteresis (∼0.6 mV) and enhanced on-current to off-current ratios (∼106). These improvements resulted in nanowire FET sensors with the lowest (∼3%) reported sensor-to-sensor variations, compared to literature studies. Also, these improved nanowire sensors have the highest reported sensitivity and enhanced signal-to-noise ratio with the lowest reported defect density of 2.1 × 1018 eV-1 cm-3, in comparison to literature data. In summary, this work brings the nanowire sensor technology a step closer to commercial products for early diagnosis and monitoring of diseases.

Apoptotic Mechanism of Human Leukemia K562/A02 Cells Induced by Magnetic Ferroferric Oxide Nanoparticles Loaded with Wogonin.

BACKGROUND: Traditional Chinese medicine wogonin plays an important role in the treatment of leukemia. Recently, the application of drug-coated magnetic nanoparticles (MNPs) to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention. Drugs coated with MNPs are becoming a promising way for better leukemia treatment. This study aimed to assess the possible molecular mechanisms of wogonin-coated MNP-Fe3O4 (Wog-MNPs-Fe3O4) as an antileukemia agent. METHODS: After incubated for 48 h, the antiproliferative effects of MNPs, wogonin, or Wog-MNPs-Fe3O4on K562/A02 cells were determined by methyl thiazolyl tetrazolium (MTT) assay. The apoptotic rates of K562/A02 cells treated with either wogonin or Wog-MNPs-Fe3O4were determined by flow cytometer (FCM) assay. The cell cycle arrest in K562/A02 cells was determined by FCM assay. The elementary molecular mechanisms of these phenomena were explored by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: With cell viabilities ranging from 98.76% to 101.43%, MNP-Fe3O4was nontoxic to the cell line. Meanwhile, the wogonin and Wog-MNPs-Fe3O4had little effects on normal human embryonic lung fibroblast cells. The cell viabilities of the Wog-MNPs-Fe3O4group (28.64-68.36%) were significantly lower than those of the wogonin group (35.53-97.28%) in a dose-dependent manner in 48 h (P < 0.001). The apoptotic rate of K562/A02 cells was significantly improved in 50 µmol/L Wog-MNPs-Fe3O4group (34.28%) compared with that in 50 µmol/L wogonin group (23.46%; P< 0.001). Compared with those of the 25 and 50 µmol/L wogonin groups, the ratios of G0/G1-phase K562/A02 cells were significantly higher in the 25 and 50 µmol/L Wog-MNPs-Fe3O4groups (all P< 0.001). The mRNA and protein expression levels of the p21 and p27 in the K562/A02 cells were also significantly higher in the Wog-MNPs-Fe3O4group compared with those of the wogonin group (all P< 0.001). CONCLUSIONS: This study demonstrated that MNPs were the effective drug delivery vehicles to deliver wogonin to the leukemia cells. Through increasing cells arrested at G0/G1-phase and inducing apoptosis of K562/A02 cells, MNPs could enhance the therapeutic effects of wogonin on leukemia cells. These findings indicated that MNPs loaded with wogonin could provide a promising way for better leukemia treatment.

Apoptotic Mechanism of Human Leukemia K562/A02 Cells Induced by Magnetic Ferroferric Oxide Nanoparticles Loaded with Wogonin / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Traditional Chinese medicine wogonin plays an important role in the treatment of leukemia. Recently, the application of drug-coated magnetic nanoparticles (MNPs) to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention. Drugs coated with MNPs are becoming a promising way for better leukemia treatment. This study aimed to assess the possible molecular mechanisms of wogonin-coated MNP-Fe3O4 (Wog-MNPs-Fe3O4) as an antileukemia agent.</p><p><b>METHODS</b>After incubated for 48 h, the antiproliferative effects of MNPs, wogonin, or Wog-MNPs-Fe3O4on K562/A02 cells were determined by methyl thiazolyl tetrazolium (MTT) assay. The apoptotic rates of K562/A02 cells treated with either wogonin or Wog-MNPs-Fe3O4were determined by flow cytometer (FCM) assay. The cell cycle arrest in K562/A02 cells was determined by FCM assay. The elementary molecular mechanisms of these phenomena were explored by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>With cell viabilities ranging from 98.76% to 101.43%, MNP-Fe3O4was nontoxic to the cell line. Meanwhile, the wogonin and Wog-MNPs-Fe3O4had little effects on normal human embryonic lung fibroblast cells. The cell viabilities of the Wog-MNPs-Fe3O4group (28.64-68.36%) were significantly lower than those of the wogonin group (35.53-97.28%) in a dose-dependent manner in 48 h (P < 0.001). The apoptotic rate of K562/A02 cells was significantly improved in 50 μmol/L Wog-MNPs-Fe3O4group (34.28%) compared with that in 50 μmol/L wogonin group (23.46%; P< 0.001). Compared with those of the 25 and 50 μmol/L wogonin groups, the ratios of G0/G1-phase K562/A02 cells were significantly higher in the 25 and 50 μmol/L Wog-MNPs-Fe3O4groups (all P< 0.001). The mRNA and protein expression levels of the p21 and p27 in the K562/A02 cells were also significantly higher in the Wog-MNPs-Fe3O4group compared with those of the wogonin group (all P< 0.001).</p><p><b>CONCLUSIONS</b>This study demonstrated that MNPs were the effective drug delivery vehicles to deliver wogonin to the leukemia cells. Through increasing cells arrested at G0/G1-phase and inducing apoptosis of K562/A02 cells, MNPs could enhance the therapeutic effects of wogonin on leukemia cells. These findings indicated that MNPs loaded with wogonin could provide a promising way for better leukemia treatment.</p>

Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD), a key enzyme involved in the catabolism of 5-fluorouracil (5-FU), is the attractive candidate for pharmacogenetic research on efficacies and toxicities of 5-FU. The aim of this study is to explore the association between polymorphisms of dihydropyrimidine dehydrogenase gene (DPYD) and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in the Chinese population. METHODS: Three hundred and sixty-two patients with gastric cancer in the Chinese population were treated with fluorouracil-based adjuvant chemotherapy. The single nucleotide polymorphic genotypes of DPYD were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) using DNA samples isolated from peripheral blood collected before treatment. RESULTS: The average response rate for chemotherapy was 46.7%. A significantly different distribution of the rs1801159 (c2=8.76, P=0.012) genotypes was observed. Homozygous genotype rs1801159A/A was over-represented in responsive patients. Conversely, carriers of the rs1801159A/G genotype were prevalent in non-responsive patients. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (c2=3.96, P=0.0465). CONCLUSIONS: These results suggest that polymorphisms of rs1801159 in DPYD may be used as valuable predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in the Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of DPYD as predictive markers for gastric cancer in response to fluorouracil-based therapies are warranted.

Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dihydropyrimidine dehydrogenase (DPD), a key enzyme involved in the catabolism of 5-fluorouracil (5-FU), is the attractive candidate for pharmacogenetic research on efficacies and toxicities of 5-FU. The aim of this study is to explore the association between polymorphisms of dihydropyrimidine dehydrogenase gene (DPYD) and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in the Chinese population.</p><p><b>METHODS</b>Three hundred and sixty-two patients with gastric cancer in the Chinese population were treated with fluorouracil-based adjuvant chemotherapy. The single nucleotide polymorphic genotypes of DPYD were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) using DNA samples isolated from peripheral blood collected before treatment.</p><p><b>RESULTS</b>The average response rate for chemotherapy was 46.7%. A significantly different distribution of the rs1801159 (c2=8.76, P=0.012) genotypes was observed. Homozygous genotype rs1801159A/A was over-represented in responsive patients. Conversely, carriers of the rs1801159A/G genotype were prevalent in non-responsive patients. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (c2=3.96, P=0.0465).</p><p><b>CONCLUSIONS</b>These results suggest that polymorphisms of rs1801159 in DPYD may be used as valuable predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in the Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of DPYD as predictive markers for gastric cancer in response to fluorouracil-based therapies are warranted.</p>