Chinese Medicine Formula Siwu-Yin Inhibits Esophageal Precancerous Lesions by Improving Intestinal Flora and Macrophage Polarization.

Siwu-Yin (SWY), a traditional Chinese medicinal formula, can replenish blood and nourish Yin. It was recorded in ancient Chinese medicine books in treating esophageal dysphagia, which has similar symptoms and prognosis with esophageal precancerous lesions and esophageal cancer. However, its effect has not been established in vivo. This study explores the antiesophageal cancer effect of SWY on rats with esophageal precancerous lesions. By performing 16S rRNA gene sequencing and metabolomics, it was suggested that SWY may improve the composition of intestinal flora of rats by regulating the synthesis and secretion of bile acids. In addition, flow cytometry results showed that SWY treatment modified tumor microenvironment by improving macrophage polarization and therefore inhibiting the occurrence of esophageal precancerous lesions.

Malignant adenomyoepithelioma of the breast: Two case reports and review of the literature.

BACKGROUND: Malignant adenomyoepithelioma (AME) of the breast is a rare tumor in which malignancy can arise from either epithelial or myoepithelial components, or from both cell types. The incidence and prognosis of malignant AME of the breast are difficult to assess due to its rarity. Therefore, the optimal treatment for this disease is still controversial. CASE SUMMARY: We present two middle-aged women (48 and 56 years old) with malignant AME of the breast. Core needle biopsy was performed before surgery. However, breast adenoma and malignant tumors were observed. The preoperative diagnosis of malignant AME of the breast is still challenging for pathologists and clinicians. Both patients underwent mastectomy and sentinel lymph node biopsy, both of which were negative, followed by adjuvant chemotherapy. CONCLUSION: The follow-up duration of the two patients was two years and four months, respectively. No signs of relapse or metastasis have been observed thus far.

Body Mass Index Changes in Relation to Male Reproductive Hormones: Longitudinal Results From a Community-Based Cohort Study.

The objective of the current study was to explore the relationship between longitudinal change in body mass index (BMI) and reproductive hormones in middle-aged and elderly Chinese men. A cohort study was conducted in a rural area of China. Local male residents aged 40-80 years were recruited at baseline in 2012 and were followed up in 2016. Information about weight, height, waist circumference, sex hormones, smoking status, and medical history were obtained. The change in BMI reported no significant relationship with the change in total testosterone (TT), calculated free testosterone (cFT), and bioavailable testosterone (BioT) in Pearson correlation analyses. When the change in BMI was divided into three groups-"great loss," "normal fluctuation," and "great gain"-TT, cFT and BioT had the highest increase (or the lowest decrease) in men with "normal fluctuation" in BMI compared with the other two groups. The advantage of maintaining a stable BMI was more evident for those who were overweight, non-smoking, and disease-free. There was a tendency of a continuous increase in cFT and BioT with BMI increase in smoking and diseased populations. Maintaining a stable BMI is associated with maintaining normal levels of reproductive hormones, especially in overweight, non-smoking, and healthy men aged over 40 years.

[Effects of Huaihuasan and baitouweng formular on rats with acute radiation proctitis and its mechanism].

Objective: To investigate the effects of huaihuasan and baitouweng formular on acute radiation proctitis (ARP) in rats. Methods: Forty clean grade SD rats were randomly divided into control group, model group, mesalazine group and formula group. Except the control group, all the other three groups received 6 MV-20 GY dose of X-ray irradiation in the pelvic cavity, and the rat model of acute radiation proctitis was established. The rats were given daily gavage intervention with the corresponding drugs after mold formation. According to the adult clinical equivalent dose (body surface area), the control group and the model group were given 10 ml/kg saline daily, the Mesalazine group was treated with Mesalazine solution at the dose of 0.27 g/kg, and the Formular group was given (0.91 g/kg) respectively for 14 days. All rats were killed on the 14th day after administration. To evaluate the general situation of the rats, HE staining was used to observe the pathological changes in the rectal tissues of the rats. The contents of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) were detected by Elisa, and the expression of NF-κb P65 in the tissues were detected by Western blot. Results: Compared with the model group, in the mesalazine group and the formular group, the clinical symptoms and intestinal mucosal healing of rats were improved significantly, the expression level of NF-κB P65 protein in the rectal tissues and the serum contents of ICAM-1 and VCAM-1 were decreased with statistically significant differences (P＜0.05). Conclusion: Huaihuasan and baitouweng formular can reduce NF-κB, ICAM-1 and VCAM-1 to improve symptoms and rectal mucosal injury in ARP rats.

Prohibitin (PHB) interacts with AKT in mitochondria to coordinately modulate sperm motility.

Prohibitin (PHB), an evolutionarily conserved mitochondrial inner membrane protein, is highly expressed in cells that require strong mitochondrial function. Recently, we demonstrated that the deletion of Phb in spermatocytes results in impaired mitochondrial function. In addition, PHB expression in the mitochondrial sheath of human sperm has a significantly negative correlation with mitochondrial reactive oxygen species levels, but a positive one with mitochondrial membrane potential and sperm motility. These results suggest that mitochondrial PHB expression plays a role in sperm motility. However, the mechanism of PHB-mediated regulation of sperm motility remains unknown. Here, we demonstrate for the first time that PHB interacts with protein kinase B (AKT) and exists in a complex with phospho-PHB (pT258) and phospho-AKT in the mitochondrial sheath of murine sperm, as determined using colocalization and coimmunoprecipitation assays. After blocking AKT activity using wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), murine sperm have significantly ( P < 0.05) decreased levels of phospho-PHB (pT258) and the total and progressive motility. Furthermore, significantly ( P < 0.05) lower levels of phospho-PI3K P85 subunit α+γ (pY199 and pY467) and phospho-AKT (pS473; pT308) are found in sperm from infertile asthenospermic and oligoasthenospermic men compared with normospermic subjects, which suggest a reduced activity of the PI3K/AKT pathway in these infertile subjects. Importantly, these sperm from infertile subjects also have a significantly ( P < 0.05) lower level of phospho-PHB (pT258). Collectively, our findings suggest that the interaction of PHB with AKT in the mitochondrial sheath is critical for sperm motility, where PHB phosphorylation (pT258) level and PI3K/AKT activity are key regulatory factors.

A Translation-Activating Function of MIWI/piRNA during Mouse Spermiogenesis.

Spermiogenesis is a highly orchestrated developmental process during which chromatin condensation decouples transcription from translation. Spermiogenic mRNAs are transcribed earlier and stored in a translationally inert state until needed for translation; however, it remains largely unclear how such repressed mRNAs become activated during spermiogenesis. We previously reported that the MIWI/piRNA machinery is responsible for mRNA elimination during late spermiogenesis in preparation for spermatozoa production. Here we unexpectedly discover that the same machinery is also responsible for activating translation of a subset of spermiogenic mRNAs to coordinate with morphological transformation into spermatozoa. Such action requires specific base-pairing interactions of piRNAs with target mRNAs in their 3' UTRs, which activates translation through coupling with cis-acting AU-rich elements to nucleate the formation of a MIWI/piRNA/eIF3f/HuR super-complex in a developmental stage-specific manner. These findings reveal a critical role of the piRNA system in translation activation, which we show is functionally required for spermatid development.

Efficacy and safety of combined high-dose interferon and red light therapy for the treatment of human papillomavirus and associated vaginitis and cervicitis: A prospective and randomized clinical study.

BACKGROUND: We evaluated the efficacy and safety of combined high-dose interferon (IFN) and red light therapy for the treatment of subclinical and latent human papillomavirus (HPV) infections. METHODS: Ninety women diagnosed with subclinical or latent HPV infection were randomized to receive topical application of low-dose recombinant IFNα-2b (1 million IU), high-dose IFNα-2b (9 million IU), or a combination of high-dose IFNα-2b and red light therapy on the cervix and vagina. All patients received treatment once daily for 4 weeks. HPV titer was measured immediately and 4, 8, and 12 weeks after treatment to determine the rates of viral clearance and infection cure. Treatment of HPV-associated vaginitis and cervicitis was also evaluated. RESULTS: Results showed that immediately and 4, 8, and 12 weeks after treatment, the HPV clearance rates and infection cure rates were higher in the high-dose IFN and combination groups compared to the low-dose IFN group. High-dose IFN and combination therapies were significantly effective against both low-risk and high-risk HPV infections. Although the cure rates for vaginitis and cervicitis were significantly higher in the high- compared to the low-dose IFN group, rates were even higher in the combination group compared to the high-dose IFN group. Mild adverse effects were reported by a very small subset of patients (3/30) in the combination group. CONCLUSIONS: This study suggests that combination of high-dose IFN and red light therapy is safe and effective against subclinical and latent HPV infections.

Recovery of paralyzed limb motor function in canine with complete spinal cord injury following implantation of MSC-derived neural network tissue.

We have reported previously that bone marrow mesenchymal stem cell (MSC)-derived neural network scaffold not only survived in the injury/graft site of spinal cord but also served as a "neuronal relay" that was capable of improving the limb motor function in a complete spinal cord injury (SCI) rat model. It remained to be explored whether such a strategy was effective for repairing the large spinal cord tissue loss as well as restoring motor function in larger animals. We have therefore extended in this study to construct a canine MSC-derived neural network tissue in vitro with the aim to evaluate its efficacy in treating adult beagle dog subjected to a complete transection of the spinal cord. The results showed that after co-culturing with neurotropin-3 overexpressing Schwann cells in a gelatin sponge scaffold for 14 days, TrkC overexpressing MSCs differentiated into neuron-like cells. In the latter, some cells appeared to make contacts with each other through synapse-like structures with trans-synaptic electrical activities. Remarkably, the SCI canines receiving the transplantation of the MSC-derived neural network tissue demonstrated a gradual restoration of paralyzed limb motor function, along with improved electrophysiological presentation when compared with the control group. Magnetic resonance imaging and diffusion tensor imaging showed that the canines receiving the MSC-derived neural network tissue exhibited robust nerve tract regeneration in the injury/graft site. Histological analysis showed that some of the MSC-derived neuron-like cells had survived in the injury/graft site up to 6.5 months. Implantation of MSC-derived neural network tissue significantly improved the microenvironment of the injury/graft site. It is noteworthy that a variable number of them had integrated with the regenerating corticospinal tract nerve fibers and 5-HT nerve fibers through formation of synapse-like contacts. The results suggest that the transplanted MSC-derived neural network tissue may serve as a structural and functional "neuronal relay" to restore the paralyzed limb motor function in the canine with complete SCI.

Increased Expression of NDRG3 in Mouse Uterus During Embryo Implantation and in Mouse Endometrial Stromal Cells During In Vitro Decidualization.

Decidualization is an indispensable event in the embryo implantation process, but its underlying molecular mechanisms remain elusive. In this study, we showed that in mice, the uterine expression of N-myc downstream-regulated gene 3 (NDRG3), a member of the α/ß hydrolase superfamily, was induced by estradiol and progesterone. During the embryo implantation process, uterine Ndrg3 expression was remarkably upregulated, and its expression level at implantation sites (IS) was significantly higher than that at inter-IS. Increased uterine expression of Ndrg3 was associated with artificial decidualization and the activation of delayed implantation. The in vitro decidualization of mouse endometrial stromal cells (ESCs) induced by estradiol and progesterone was also accompanied by increased Ndrg3 expression, and downregulated Ndrg3 expression in ESCs effectively inhibited decidualization. miR-290b-5p was identified as an upstream regulator of Ndrg3, and the uterine expression level of miR-290b-5p was decreased during the implantation process. Furthermore, overexpression of miR-290b-5p in mouse ESCs inhibited their in vitro decidualization. Taken together, these data suggested that Ndrg3 might play an important role in embryo implantation by regulating decidualization potentially via the estrogen/progesterone/miR-290b-5p pathway.

Nuclear G protein-coupled oestrogen receptor (GPR30) predicts poor survival in patients with ovarian cancer.

Objective To demonstrate the correlation between nuclear and cytoplasmic G protein-coupled oestrogen receptor (GPR30) expression and clinicopathological features and outcome in patients with ovarian cancer. Methods Nuclear and cytoplasmic GPR30 expressions were determined using immunohistochemistry to identify the intracellular location in tissues from patients with ovarian cancer. Data were correlated with clinicopathological characteristics and outcomes. Results Tissue samples were obtained from 110 patients with epithelial ovarian cancer between 2005 and 2010. Nuclear GPR30 was significantly more frequent in the group of patients with recurrence. The presence of nuclear GPR30 predicted lower overall survival) and 5-year progression-free survival in all patients with ovarian cancer and overall survival in patients with high grade ovarian cancer. Cytoplasmic GPR30 was observed significantly more often in advanced ovarian cancer and did not predict survival. Conclusion This study showed that nuclear GPR30 is an independent negative prognostic indicator in patients with ovarian cancer, especially in those with a high grade malignancy.

Reproductive effects of cadmium on sperm function and early embryonic development in vitro.

Cadmium is a major environmental toxicant that is released into the atmosphere, water and soil in the form of cadmium oxide, cadmium chloride, or cadmium sulfide via industrial activities, such as the manufacturing of batteries and pigments, metal smelting and refining and municipal waste incineration. In the present study, we investigated the effects of cadmium exposure on sperm quality parameters, fertilization capacity and early embryonic development. Our study showed that in vitro incubation of human or mouse sperms with cadmium for a long time (up to 24 hours) could significantly decreased sperm motility in a concentration- and time-dependent manner. Exposure to cadmium in the environment for a short term (30 min) did not affect sperm motility but significantly reduced in vitro fertilization rate. We also evaluated the effects of cadmium at concentrations of 0.625 µg/ml, and 1.25 µg/ml on early embryonic development in vitro and observed that the blastocyst formation rate dramatically decreased with increasing cadmium concentration. This finding emphasizes the hazardous effects of cadmium on sperm quality as well as on natural embryo development and raises greater concerns regarding cadmium pollution.

High PD-L1 Expression Is Closely Associated With Tumor-Infiltrating Lymphocytes and Leads to Good Clinical Outcomes in Chinese Triple Negative Breast Cancer Patients.

BACKGROUND: To investigate the role of Programmed death ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in tumor recurrence and metastasis of Chinese patients suffering from triple negative breast cancer (TNBC). METHODS: PD-L1 immunohistochemistry was performed on 215 TNBCs. Also, the prevalence of TILs correlated the expression of PD-L1 and TILs with clinical outcomes. Kaplan-Meier and the model analyses of univariate Cox proportional hazards were utilized to compare the survival of patients with positive PD-L1 expression with those with negative PD-L1 expression. RESULTS: The median follow-up time was 67.7 months (range: 7-159 months). PD-L1-positive breast cancer patients had significantly longer disease-free survival (DFS) and Overall survival (OS) compared with PD-L1-negative patients (P=0.046; P=0.019) in TNBC. The presence of increased stromal lymphocytic infiltrates (STILs) was significantly associated with overall survival (P=0.026). The model analysis of univariate Cox proportional hazards showed that PD-L1 and STILs were independent prognostic factors for tumor prognosis. CONCLUSIONS: Our study found that high levels of PD-L1 could be expressed in TNBC, which was correlated with the prevalence of TILs.

Uterine Expression of NDRG4 Is Induced by Estrogen and Up-Regulated during Embryo Implantation Process in Mice.

Embryo implantation is an essential step for the establishment of pregnancy and dynamically regulated by estrogen and progesterone. NDRG4 (N-myc down-regulated gene 4) is a tumor suppressor that participates in cell survival, tumor invasion and angiogenesis. The objective of this study was to preliminarily explore the role of NDRG4 in embryo implantation. By immunohistochemistry (IHC) and quantitive RT-PCR (qRT-PCR), we found that uterine expression of NDRG4 was increased along with puberal development, and its expression in adult females reached the peak at the estrus stage during the estrus cycle. Furthermore, uterine NDRG4 expression was significantly induced by the treatment of estradiol (E2) both in pre-puberty females and ovariectomized adult females. Uterine expression pattern of NDRG4 during the peri-implantation period in mice was determined by IHC, qRT-PCR and Western blot. It was observed that NDRG4 expression was up-regulated during the implantation process, and its expression level at the implantation sites was significantly higher than that at the inter-implantation sites. Meanwhile, an increased expression in NDRG4 was associated with artificial decidualization as well as the activation of delayed implantation. By qRT-PCR and Western blot, we found that the in vitro decidualization of endometrial stromal cells (ESCs) was accompanied by up-regulation of NDRG4 expression, whereas knockdown of its expression in these cells by siRNA inhibited the decidualization process. In addition, Western blot analysis showed that NDRG4 protein expression was decreased in human villus tissues of recurrent miscarriage (RM) patients compared to normal pregnant women. Collectively, these data suggested that uterine NDRG4 expression could be induced by estrogen, and NDRG4 might play an important role during early pregnancy.

Point mutations in KAL1 and the mitochondrial gene MT-tRNA(cys) synergize to produce Kallmann syndrome phenotype.

Kallmann syndrome (KS) is an inherited developmental disorder defined as the association of hypogonadotropic hypogonadism and anosmia or hyposmia. KS has been shown to be a genetically heterogeneous disease with different modes of inheritance. However, variants in any of the causative genes identified so far are only found in approximately one third of KS patients, thus indicating that other genes or pathways remain to be discovered. Here, we report a large Han Chinese family with inherited KS which harbors two novel variants, KAL1 c.146G>T (p.Cys49Phe) and mitochondrial tRNA(cys) (m.5800A>G). Although two variants can't exert obvious effects on the migration of GnRH neurons, they show the synergistic effect, which can account for the occurrence of the disorder in this family. Furthermore, the disturbance of the mitochondrial cysteinyl-tRNA pathway can significantly affect the migration of GnRH cells in vitro and in vivo by influencing the chemomigration function of anosmin-1. Our work highlights a new mode of inheritance underlay the genetic etiology of KS and provide valuable clues to understand the disease development.

MiR-218 inhibits multidrug resistance (MDR) of gastric cancer cells by targeting Hedgehog/smoothened.

Multidrug resistance (MDR) is the main obstacle to successful chemotherapy for patients with gastric cancer. The microRNA miR-218 influences various pathobiological processes in gastric cancer, and its down-regulation in this disease raises the question of whether it normally inhibits MDR. In this study we observed that two MDR gastric cancer cell lines showed lower expression of miR-218 compared with their chemosensitive parental cell line. Overexpressing miR-218 chemosensitizes gastric cancer cells, slowed efflux of adriamycin, and accelerated drug-induced apoptosis. We identified the smoothened (SMO) gene as a functional target of miR-218, and found that SMO overexpression counteracts the chemosensitizing effects of miR-218. These findings suggest that miR-218 inhibits MDR of gastric cancer cells by down-regulating SMO expression.

Effect of nitrogen and phosphorus deficiency on transcriptional regulation of genes encoding key enzymes of starch metabolism in duckweed (Landoltia punctata).

The production of starch by plants influences their use as biofuels. Nitrogen (N) and phosphorus (P) regulate starch gene expression during plant growth and development, yet the role of key enzymes such as ADP-glucose pyrophosphorylase (E.C. 2.7.7.27 AGPase) in starch metabolism during N- and P-deficiency remains unknown. We investigated the effect of N- and P-deficiency on the expression of large (LeAPL1, LeAPL2, and LeAPL3) and small (LeAPS) subunits of AGPase in duckweed (Landoltia punctata) and their correlation with starch content. We first isolated the full-length cDNA encoding LeAPL1 (GenBank Accession No. KJ603244) and LeAPS (GenBank Accession No. KJ603243); they contained open reading frames of 1554 bp (57.7-kDa polypeptide of 517 amino acids) and 1578 bp (57.0 kDa polypeptide of 525 amino acids), respectively. Real-time PCR analysis revealed that LeAPL1 and LeAPL3 were highly expressed during early stages of N-deficiency, while LeAPL2 was only expressed during late stage. However, in response to P-deficiency, LeAPL1 and LeAPL2 were upregulated during early stages and LeAPL3 was primarily expressed in the late stage. Interestingly, LeAPS was highly expressed following N-deficiency during both stages, but was only upregulated in the early stage after P-deficiency. The activities of AGPase and soluble starch synthesis enzyme (SSS EC 2.4.1.21) were positively correlated with changes in starch content. Furthermore, LeAPL3 and LeSSS (SSS gene) were positively correlated with changes in starch content during N-deficiency, while LeAPS and LeSSS were correlated with starch content in response to P-deficiency. These results elevate current knowledge of the molecular mechanisms underlying starch synthesis.

MicroRNA-218 is upregulated in gastric cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and increases chemosensitivity to cisplatin.

AIM: To investigate the molecular mechanisms of miRNA in advanced gastric cancers (AGCs) before and after cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A miRNA microarray containing human mature and precursor miRNA sequences was used to compare expression profiles in serum samples of 5 patients with AGC before and after CRS + HIPEC. The upregulation of miR-218 was confirmed by real-time reverse transcription polymerase chain reaction and its expression was analyzed in SGC7901 gastric cancer cells. RESULTS: miRNA microarray chip analysis found that the level of miR-218 expression was upregulated more than 8 fold after CRS + HIPEC. Furthermore, miR-218 increased gastric cancer cell chemosensitivity to cisplatin in vitro and inhibited gastric cell tumor growth in nude mice in vivo (0.5 vs 0.78, P < 0.05). CONCLUSION: Our results indicated that targeting miR-218 may provide a strategy for blocking the development of gastric cancer and reverse the multi-drug resistance of gastric cell lines.

Targeting the anaphase-promoting complex/cyclosome (APC/C)- bromodomain containing 7 (BRD7) pathway for human osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor in childhood and adolescence and has a propensity for local invasion and early lung metastasis. However, the current therapies often result in chemoresistance, and a therapeutic target is not available in the clinic for osteosarcoma. Here, we report that BRD7 forms a complex with the anaphase-promoting complex/cyclosome (APC/C) and is degraded by APC/C(cdh1) and APC/C(cdc20) during the cell cycle. Moreover, BRD7 is a tumor suppressor in osteosarcoma, and the BRD7 mutant resistant to degradation by APC/C is more efficient than the wild-type protein at suppressing proliferation, colony formation, and tumor growth of osteosarcoma in vitro and in vivo. The combination of proTAME, an inhibitor of APC/C, with chemotherapeutic drugs efficiently targets osteosarcoma in vitro. Furthermore, there is a strong inverse correlation of protein levels between BRD7 and Cdh1 or Cdc20, and lower BRD7 expression is an indicator for poor prognosis in patients with osteosarcoma. Collectively, our results indicate that targeting the APC/C-BRD7 pathway may be a novel strategy for treating osteosarcoma.

The Prognostic Value of p16 Hypermethylation in Cancer: A Meta-Analysis.

BACKGROUND: The prognostic value of p16 promoter hypermethylation in cancers has been evaluated for several years while the results remain controversial. We thus performed a systematic review and meta-analysis of studies assessing the impact of p16 methylation on overall survival (OS) and disease-free survival (DFS) to clarify this issue. METHODS: We searched Pubmed, Embase and ISI web of knowledge to identify studies on the prognostic impact of p16 hypermethylation in cancers. A total of 6589 patients from 45 eligible studies were included in the analysis. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to estimate the effect using random-effects model. RESULTS: The analysis indicated that p16 hypermethylation had significant association with poor OS of non-small cell lung cancer (NSCLC) (HR 1.74, 95% CI: 1.36-2.22) and colorectal cancer (CRC) (HR 1.80; 95% CI 1.27-2.55). Moreover, the significant correlation was present between p16 hypermethylation and DFS of NSCLC (HR 2.04, 95% CI: 1.19-3.50) and head and neck cancer (HR 2.24, 95% CI: 1.35-3.73). Additionally, in the analysis of the studies following REMARK guidelines more rigorously, p16 hypermethylation had unfavorable impact on OS of NSCLC (HR 1.79, 95% CI: 1.35-2.39) and CRC (HR 1.96, 1.16-3.34), and on DFS of NSCLC (HR 2.12, 95% CI: 1.21-3.72) and head and neck cancer (HR 2.24, 95% CI: 1.35-3.73). CONCLUSIONS: p16 hypermethylation might be a predictive factor of poor prognosis in some surgically treated cancers, particularly in NSCLC.

[Exploration of the correlation between Chinese medicine syndrome types of verrucous gastritis and the pressions of gastric mucosal hypoxia-inducible factor-1alpha as well as downstream molecules].

OBJECTIVE: To study the expressions changes of gastric mucosal hypoxia-inducible factor-1alpha (HIF-1alpha) and downstream molecules [such as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2)] of verrucous gastritis (VG) patients of different Chinese medicine (CM) syndrome types and their clinical significance. METHODS: Totally 94 VG patients were assigned to Gan-Wei disharmony group (GWDG, 28 cases), the damp-heat in Pi-Wei group (DHPWG, 17 cases), the blood stasis in Wei-collateral group (BSWCG, 20 cases), and the insufficiency of Pi-yang group (IPYG, 29 cases). Another 30 patients with chronic mild non-active superficial gastritis patients accompanied with negative Hp infection were recruited as the control group. The Hp infection was detected using 14C-labeled urea breath test. The expressions of HIF-1alpha, VEGF, and COX-2 in the gastric mucosal tissue were detected using immunohistochemical EnVision two-step test. RESULTS: The positive Hp infection rate in VG patients was 37.23% (35/94 cases). The positive Hp infection rate in patients of DHPWG (76. 47%) was significantly higher than the other three groups (32.14% in GWDG, 31.03% in IPYG, and 20.00% in BSWCG, P < 0.01). The expressions of HIF-1alpha and COX-2 in VG patients of different syndrome types were obviously higher than those of the control group (P < 0.01, P < 0.05). Of them, the expression of HIF-1alpha was the highest in BSWCG and the expression of COX-2 was the highest in DHPWG. The expression of VEGF was higher in DHPWG and IPYG than in the control group and the GWDG (P < 0.01, P < 0.05). CONCLUSIONS: The expressions of HIF-1alpha, VEGF, COX-2, and Hp infection showed certain changes in VG patients of different syndrome types. The expression of HIF-1alpha was the strongest in BSWCG. The expressions of VEGF and COX-2 as well as Hp infection were the highest in DHPWG. All showed the specificity of CM syndromes.