Cardiovascular Protective Effects of Oral Hypoxia Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat in the Treatment of Type 4 Cardiorenal-Anemia Syndrome: Protocol of a Randomized Controlled Trial.

Background: Patients with chronic kidney disease (CKD) are at high risk of developing heart failure and anemia, which is defined as type 4 cardiorenal-anemia syndrome (CRAS). CRAS aggravates the deterioration of both kidney and heart function, ultimately resulting in a high mortality. This study aims to examine the efficacy and safety of roxadustat in the treatment of type 4 CRAS. Methods and Design: This study is designed as a randomized, open-label, controlled trial. A total of 68 patients diagnosed with type 4 CRAS will be randomly divided into roxadustat group and erythropoietin with a 1:1 ratio. Participants in the roxadustat group will receive roxadustat with an initial dose of 70 or 100 mg three times a week, and participants in the erythropoietin group will receive subcutaneous injection of erythropoietin for 24 weeks, to maintain a hemoglobin ranging from 100 to 120 g per liter. The primary outcome is the change in heart function, including brain natriuretic peptide (BNP), 6-min walk test (6-WT), and left ventricular ejection fraction (LVEF). Secondary outcomes to be assessed include death, cardiovascular events, hospitalization regarding heart failure, Minnesota Heart Failure Quality of life scale (MLHFQ) score, New York Heart Association (NYHA) cardiac function grade, echocardiographic parameters including left ventricular diastolic diameter and volume (LVDD and LVDV) and ventricular mass (LVM), anemia related parameters, inflammatory parameters, and safety assessments. Conclusion: The findings of this study will provide potential evidence for roxadustat in CRAS management. Trial Registration: Chinese Clinical Trial Registry, ID: ChiCTR2100050031. Registered on 16 August 2021.

A Network Pharmacology Approach to Explore the Mechanism of HuangZhi YiShen Capsule for Treatment of Diabetic Kidney Disease.

BACKGROUND AND OBJECTIVE: HuangZhi YiShen Capsule (HZYS) is a Chinese patent herbal drug that protects kidney function in diabetic kidney disease (DKD) patients. However, the pharmacologic mechanisms of HZYS remain unclear. This study would use network pharmacology to explore the pharmacologic mechanisms of HZYS. METHODS: Chemical constituents of HZYS were obtained through the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and literature search. Potential targets of HZYS were identified by using the TCMSP and the SwissTarget Prediction databases. DKD-related target genes were collected by using the Online Mendelian Inheritance in Man, Therapeutic Target Database, GeneCards, DisGeNET, and Drugbank databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the mechanisms of HZYS in treating DKD. Molecular docking was conducted to verify the potential interactions between the prime compounds and the hub genes. RESULTS: 179 active compounds and 620 target genes were obtained, and 571 common targets were considered potential therapeutic targets. The top 10 main active compounds of HZYS were heparin, quercetin, kaempferol, luteolin, methyl14-methylpentadecanoate, methyl (Z)-11-hexadecenoate, 17-hydroxycorticosterone, 4-pregnene-17α, 20ß, 21-triol-3, 11-dione, wogonin, and hydroxyecdysone. Hub signaling pathways by which HZYS treating DKD were PI3K-Akt, MAPK, AGE-RAGE in diabetic complications, TNF, and apoptosis. The top 10 target genes associated with these pathways were IL6, MAPK1, AKT1, RELA, BCL2, JUN, MAPK3, MAP2K1, CASP3, and TNF. Quercetin and Luteolin were verified to have good binding capability with the hub potential targets IL6, MAPK1, AKT1 through molecular docking. CONCLUSION: HZYS appeared to treat DKD by regulating the inflammatory, oxidative stress, apoptotic, and fibrosis signaling pathways. This study provided a novel perspective for further research of HZYS.

Association of Epoxide Hydrolase 2 Gene Arg287Gln with the Risk for Primary Hypertension in Chinese.

BACKGROUND: Epoxide hydrolase 2 (EPHX2) gene coding for soluble epoxide hydrolase is a potential candidate in the pathogenesis of hypertension. OBJECTIVES: We aimed to assess the association of a missense mutation, R287Q, in EPHX2) gene coding for soluble epoxide hydrolase is a potential candidate in the pathogenesis of hypertension. METHODS: This study involved 782 patients with primary hypertension and 458 healthy controls. Genotyping was done using TaqMan technique. Activity of soluble epoxide hydrolase fusion proteins was evaluated by the conversion of 11,12-EET to corresponding 11,12-DHET using ELISA kit. RESULTS: After taking carriers of R287Q variant GG genotype as a reference, those with GA genotype had a significantly reduced risk of hypertension (adjusted odds ratio: 0.72, 95% confidence interval: 0.56 to 0.93, P = 0.013). Five significant risk factors were identified, including age, body mass index, total cholesterol, homocysteine, and R287Q variant. These five risk factors for hypertension were represented in a nomogram, with a descent prediction accuracy (C-index: 0.833, P = 0.013). Five significant risk factors were identified, including age, body mass index, total cholesterol, homocysteine, and R287Q variant. These five risk factors for hypertension were represented in a nomogram, with a descent prediction accuracy (C-index: 0.833. CONCLUSIONS: We provide evidence that R287Q mutation in EPHX2 gene was associated with reduced risk of primary hypertension and low activity of soluble epoxide hydrolase.EPHX2) gene coding for soluble epoxide hydrolase is a potential candidate in the pathogenesis of hypertension.

Chinese medicine for diabetic kidney disease in China.

Diabetic kidney disease (DKD) is a major global public health concern due to its high prevalence and mortality, and high healthcare cost. Conventional Western therapies for DKD fail to provide favourable efficacy. Chinese medicine (CM) has been widely used to combat DKD in China and other Asian countries. The clinical effects and mechanism of CM in treating DKD have not been fully elucidated. This review summarizes current knowledge of CM therapeutic modalities for DKD, especially Chinese herbal medicine (CHM), and potential mechanisms.

Effects of Tangshen Formula on urinary and plasma liver-type fatty acid binding protein levels in patients with type 2 diabetic kidney disease: post-hoc findings from a multi-center, randomized, double-blind, placebo-controlled trial investigating the efficacy and safety of Tangshen Formula in patients with type 2 diabetic kidney disease.

BACKGROUND: Tangshen Formula (TSF) is a traditional Chinese medicine for the treatment of diabetic kidney disease (DKD). Liver-type fatty acid binding protein (L-FABP) is expressed in various tissues, including the kidney, where it is known as urinary L-FABP. Other studies demonstrated that urinary L-FABP may be a useful biomarker for monitoring DKD. This post-hoc analysis and cross-sectional study evaluated the changes in urinary L-FABP in DKD patients treated with TSF and conventional medicine. METHODS: Post-hoc analysis was conducted on a multicenter, randomized, double-blind, placebo-controlled trial. A total of 180 participants with DKD including 98 with microalbuminuria and 82 with macroalbuminuria were enrolled in the original study. In addition to conventional treatment, 122 participants were randomly assigned to receive TSF and 58 to receive placebo. After 24-weeks of treatment, the intention-to-treat population in microalbuminuria stage was 56 in the TSF group and 25 in the placebo group, and in the macroalbuminuria stage 42 and 19, respectively. The primary outcome in the original trial was urinary protein level. In the current study, urinary and plasma L-FABP levels were measured in 30 microalbuminuria patients (15 in the TSF group and 15 in the placebo group) and 30 macroalbuminuria patients (15 in the TSF group and 15 in the placebo group). In addition, another 30 patients with normoalbuminuria (urinary albumin excretion rate (UAER) < 20 µg/min) were recruited for the cross-sectional study. RESULTS: (1) In microalbuminuria patients, UAER in the TSF group displayed a significant decrease after 24 weeks of treatment (P = 0.045). Levels of urinary L-FABP in the TSF group were markedly lower than in the placebo group after 12 and 24 weeks (P = 0.004 and P = 0.047, respectively). (2) In macroalbuminuria patients, 24-h urinary protein levels decreased significantly compared with baseline in the TSF group at week 12 (P = 0.042) and week 24 (P = 0.041). The TSF group showed a significant decrease in urinary L-FABP after 12 and 24 weeks (P = 0.036 and P = 0.046, respectively). (3) Levels of urinary L-FABP increased markedly, correlating with severity of DKD. L-FABP in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria were 5.9 (5.2, 7.8) µg/ml, 11.4 (6.8, 13.4) µg/ml and 18.5 (10.9, 23.4) µg/ml, respectively (P = 0.000). CONCLUSIONS: TSF combined with conventional therapy appeared to be effective in reducing urinary protein and urinary L-FABP. Urinary L-FABP levels appear to be associated with the severity of DKD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-10000843 . Registered 15 April 2010.

Chinese herbal medicine Tangshen Formula treatment of patients with type 2 diabetic kidney disease with macroalbuminuria: study protocol for a randomized controlled trial.

BACKGROUND: Diabetic kidney disease (DKD) is one of the most common microvascular complications of diabetes mellitus and the main cause of end-stage renal disease. Present medications for DKD are not entirely satisfactory. Preliminary studies indicate that the Chinese herbal formula Tangshen Formula (TSF) appears to decrease the proteinuria and improve the estimated glomerular filtration rate (eGFR) in DKD patients. METHODS/DESIGN: This trial is a five-center, randomized, double-blind, placebo-controlled study. DKD patients with a 24-h urinary protein (24 h UP) level between 0.5 and 3.5 g and serum creatinine < 265 µmol/L (3 mg/dl) will be included. A sample size of 144 participants will be randomly distributed into the treatment group (TSF plus irbesartan) and the control group (placebo plus irbesartan) at a ratio of 1:1. The study duration will be 50 weeks, comprising a 2-week run-in period, 24 weeks of intervention, and 24 weeks of follow-up. The primary endpoint will be the 24 h UP. Secondary endpoints will be an evaluation of renal function, management of blood lipids, improvement in traditional Chinese medicine symptoms, and safety assessments. Adverse events will also be evaluated. DISCUSSION: This study will provide evidence for the effectiveness and safety of TSF compared to placebo in treating DKD patients with macroalbuminuria. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR-TRC-13003566 . Registered 9 August 2013.

Yi Qi Qing Re Gao-containing serum inhibits lipopolysaccharide-induced rat mesangial cell proliferation by suppressing the Wnt pathway and TGF-ß1 expression.

The aim of the present study was to investigate the effect of Yi Qi Qing Re Gao-containing serum (YQ-S) on rat mesangial cell (MC) proliferation and to investigate the underlying mechanism. MCs were divided into the control, lipopolysaccharide (LPS)-stimulated, YQ-S and fosinopril-containing serum (For-S) groups, and cultured for 48 h. An MTT assay was used to evaluate the proliferation of MCs. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were conducted to detect the expression levels of Wnt4, ß-catenin and transforming growth factor (TGF)-ß1 in MCs. The results indicated that YQ-S inhibited LPS-induced MC proliferation. The Wnt4 and TGF-ß1 mRNA expression levels were reduced in the YQ-S group (P<0.01 or P<0.05). Furthermore, the Wnt4, ß-catenin and TGF-ß1 protein expression levels were suppressed in the YQ-S group (P<0.01 or P<0.05). Therefore, YQ-S appears to inhibit MC proliferation, and its mechanism may involve the inhibition of the Wnt signaling pathway and downregulation of TGF-ß1 expression.

Therapeutic Effects of Tangshen Formula on Diabetic Nephropathy in Rats.

OBJECTIVE: Inflammation and fibrosis are essential promoters in the pathogenesis of diabetic nephropathy (DN) in type 2 diabetes. The present study examined the anti-inflammation and anti-fibrosis effect of Tangshen Formula (TSF), a traditional Chinese medicine, on DN. RESEARCH DESIGN AND METHODS: Protective role of TSF in DN was examined in a rat model of type 2 DN that was established by high-fat diet-fed and low-dose-streptozotocin injection. TSF was suspended in 0.5% CMC-Na solution and delivered by oral gavage at a dosage of 1.67g/Kg body weight/day. The therapeutic effects and mechanisms of TSF on diabetic kidney injury were examined. RESULTS: We found that TSF treatment for 20 weeks attenuated DN by significantly inhibiting urinary excretion of albumin and renal histological injuries. These beneficial effects were associated with an inactivation of NF-κB signaling, thereby blocking the upregulation of pro-inflammatory cytokines (IL-1ß, TNFα), chemokine (MCP-1), and macrophage infiltration in the TSF-treated rats with type 2 DN. In addition, TSF treatment also inactivated TGF-ß/Smad3 signaling and therefore suppressed renal fibrosis including expressions of fibronectin, collagen I, and collagen IV. Further studies revealed that the inhibitory effect of TSF on TGF-ß/Smad3 and NF-κB signaling in DN was associated with inhibition of Smurf2-dependent ubiquitin degradation of Smad7. CONCLUSIONS: The present study reveals that TSF has therapeutic potential for type 2 DN in rats. Blockade of NF-κB-driven renal inflammation and TGF-ß/Smad3-mediated renal fibrosis by preventing the Smurf2-mediated Smad7 degradation pathway may be mechanisms through which TSF inhibits type 2 DN.

Onychomycosis Associated with Exophiala oligosperma in Taiwan.

A fungus was isolated from a nail of a 54-year-old female patient with onychomycosis in Taiwan. Based on ITS rDNA as well as beta tubulin gene sequences and microscopic analyses, this fungus was identified as Exophiala oligosperma. This is the first record of E. oligosperma in Taiwan. Negative keratin azure test indicates that keratin degradation is not involved in cases of E. oligosperma associated with skin and nail diseases.

Efficacy and safety of tangshen formula on patients with type 2 diabetic kidney disease: a multicenter double-blinded randomized placebo-controlled trial.

BACKGROUND: Persons with diabetes are at high risk of developing diabetic kidney disease (DKD), which is associated with high morbidity and mortality. Current drug therapies for DKD, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are not entirely satisfactory. This study aimed to evaluate the additional benefit and safety of the Chinese herbal granule Tangshen Formula (TSF) in treating DKD. METHODS: The study was designed as a six-center randomized, double-blind, placebo-controlled trial. From April 2007 through December 2009, 180 patients with DKD were enrolled. In addition to conventional treatment with ACEIs or ARBs, 122 participants were randomly assigned to receive TSF and 58 participants to receive placebo for 24 weeks. Primary outcome was urinary protein level, measured by urinary albumin excretion rate (UAER) for participants with microalbuminuria, 24-hour urinary protein (24h UP) for participants with macroalbuminuria. Secondary outcomes included renal function, serum lipids, quality of life, symptoms, and adverse events. FINDINGS: After 24 weeks of treatment, no statistically significant difference in UAER (TSF -19.53 µg/min compared with placebo -7.01 µg/min, with a mean difference of -12.52 µg/min; 95%CI, -68.67 to 43.63, P = 0.696) was found between TSF and placebo groups. However, TSF displayed a statistically significant decrease in 24h UP (TSF-0.21 g compared with placebo 0.36 g, with a mean difference of -0.57g; 95%CI, -1.05 to -0.09, P = 0.024). Estimated glomerular filtration rate (eGFR) was improved in both patients with microalbuminuria and macroalbuminuria, with a mean difference of 15.51 ml/min/1.73 m2 (95%CI, 3.71 to 27.31), 9.01 ml/min/1.73 m2 (95%CI, -0.10 to 18.13), respectively. Other secondary outcomes showed no statistically significant difference between groups or in the incidence of adverse events. CONCLUSIONS: Based on conventional treatments, TSF appears to provide additional benefits compared with placebo in decreasing proteinuria and improving eGFR in DKD patients with macroalbuminuria. Nevertheless, further study is needed to evaluate TSF treating patients with microalbuminuria. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-10000843.

Yi Qi Qing Re Gao formula ameliorates puromycin aminonucleoside-induced nephrosis by suppressing inflammation and apoptosis.

BACKGROUND: Yi Qi Qing Re Gao (YQQRG) formula is a traditional Chinese herbal medicine used to treat chronic nephritis. This study was designed to evaluate the underlying mechanism in the use of YQQRG formula to treat nephrosis induced by puromycin aminonucleoside (PAN). METHODS: Thirty-six male Wistar rats were randomly divided into 3 groups of 12 rats each: a sham group, a vehicle-treated PAN model group (PAN), and a group treated with YQQRG (PAN + YQQRG). The PAN model was established by a single intravenous injection of PAN at a dose of 40 mg/kg body weight; rats in the sham group received the same volume of saline. Twenty-four hour urinary protein was measured 0, 3, 5, 10, and 15 days after the injection. The rats were sacrificed on day 10 and day 15 and the serum lipid profile examined. The renal cortex of each rat was stained with periodic acid-Schiff reagent and the pathologic alterations and ultrastructural changes were examined by transmission electron microscopy. In situ cell apoptosis was detected by a terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) assay. Transcriptive levels of inflammatory markers and molecules associated with apoptosis were detected by a real-time polymerase chain reaction and expression of proteins was examined by either immunohistochemistry or Western blot analysis. RESULTS: YQQRG significantly decreased urinary protein level, and lowered serum lipid level. YQQRG also attenuated histologic lesions in the rat kidneys. Activation of inflammatory markers was largely restored by the administration of YQQRG. TUNEL assay showed that YQQRG decreased the number of apoptotic cells. Both mRNA and protein levels of caspase-3 were significantly reduced in the group treated with YQQRG, whereas expression of the Bcl-2 protein increased in the YQQRG group. CONCLUSIONS: YQQRG alleviated kidney injury in PAN-treated rats, possibly through anti-inflammatory and anti-apoptotic effects.

Renoprotective effect of berberine on type 2 diabetic nephropathy in rats.

Inflammation, fibrosis, and lipid disorder are essential promoters in the pathogenesis of diabetic kidney injury in diabetes mellitus type 2. Berberine (BBR) has been reported to have beneficial effects on diabetic nephropathy, but its action mechanism is still unclear. The present study was designed to elucidate the therapeutic mechanism of BBR in a type 2 diabetic nephropathy rat model induced by a high-fat diet and low-dose streptozotocin injection. The diabetic rats were treated with or without BBR by gavage for 20 weeks and examined by serology, 24-h albuminuria, histology, immunohistochemistry, and molecular analyses. Results showed that treatment with BBR significantly reduced serum levels of blood glucose and lipids, inhibited urinary excretion of albumin, and attenuated renal histological injuries in diabetic rats. Berberine treatment also inhibited renal inflammation, which was associated with inactivation of nuclear factor kappa-light-chain-enhancer of activated B-cell signalling. As a result, the upregulation of pro-inflammatory cytokines (interleukin-1ß, tumour necrosis factor-α) and chemokine (monocyte chemotactic protein-1) was blocked. In addition, BBR treatment also inactivated transforming growth factor-ß/Smad3 signalling and suppressed renal fibrosis, including expression of fibronectin, collagen I, and collagen IV. The present study reveals that BBR is a therapeutic agent for attenuating type 2 diabetic nephropathy by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cell-driven renal inflammation and transforming growth factor-ß/Smad3 signalling pathway.

Yi qi qing re gao attenuates podocyte injury and inhibits vascular endothelial growth factor overexpression in puromycin aminonucleoside rat model.

Proteinuria is the hallmark of chronic kidney disease. Podocyte damage underlies the formation of proteinuria, and vascular endothelial growth factor (VEGF) functions as an autocrine/paracrine regulator. Yi Qi Qing Re Gao (YQQRG) has been used to treat proteinuria for more than two decades. The objective of this study was to investigate the protective effect and possible mechanisms of YQQRG on puromycin aminonucleoside (PAN) rat model. Eighty male Sprague-Dawley rats were randomized into sham group, PAN group, PAN + YQQRG group, and PAN + fosinopril group. Treatments were started 7 days before induction of nephrosis (a single intravenous injection of 40 mg/kg PAN) until day 15. 24 h urinary samples were collected on days 5, 9, and 14. The animals were sacrificed on days 3, 10, and 15, respectively. Blood samples and renal tissues were obtained for detection of biochemical and molecular biological parameters. YQQRG significantly reduced proteinuria, elevated serum albumin, and alleviated renal pathological lesions. YQQRG inhibited VEGF-A, nephrin, podocin, and CD2AP mRNA expression and elevated nephrin, podocin, and CD2AP protein levels starting on day 3. In conclusion, YQQRG attenuates podocyte injury in the rat PAN model through downregulation of VEGF-A and restoration of nephrin, podocin, and CD2AP protein expression.

Management of parapharyngeal-space tumors.

PURPOSE: This study evaluated parapharyngeal-space (PPS) tumors in regard to clinical pathological features, preoperative assessment, surgical approaches, perioperative complications, and patterns of recurrence. PATIENTS AND METHODS: We performed a retrospective review of patients with PPS tumors referred to the stomatological hospitals of Sichuan University and Xi'an Jiaotong University between 1990 and 2004. RESULTS: Beginning in 1990 and ending in 2004, 162 patients with PPS tumors were evaluated in our unit. The gender distribution was 94 (58.08%) males and 68 (41.98%) females. The median age was 36.4 years. The main presenting symptom was neck swelling. All cases were evaluated with at least a computed tomography scan. The most common class of lesion was salivary-gland neoplasm, accounting for 74 cases (45.68%). The next most common group of tumors was neurogenic, representing 68 cases (41.98%). Only 22 patients (13.58%) presented with malignant disease. Three surgical approaches were commonly used in the management of these lesions: transcervical-transparotid in 93 patients (57.41%), transcervical in 51 patients (31.48%), and transcervical-transmandibular in 18 patients (11.11%). Twenty patients with malignant disease underwent adjuvant chemotherapy and/or radiotherapy. All cases were followed for a mean of 36 months. There was no perioperative mortality. Two patients suffered local failure, and 4 patients developed distant metastasis during the observation period. CONCLUSIONS: Surgery is the mainstay treatment for PPS tumors. Surgical approaches were dictated by size of the tumor, its location, its relationship to the great vessels, and suspicion of malignancy. The most common approach was transcervical-transparotid for benign tumors.

Management of infant ranula.

OBJECTIVE: Many surgical techniques to manage ranulas have been described in the literature. Ranula of infant patients was rare. Few studies have described the approach toward management in infant patients. METHODS: Eleven infant patients were treated for intraoral ranulas. The methods of treatment included aspiration of mucus, marsupialization and excision of the ranula and the ipsilateral sublingual gland. All cases were performed aspiration of mucus and observed for 6 months; and the marsupialization were recommended if the ranula recurred; the surgical resection of ipsilateral sublingual gland were performed if the ranula recurred when infant patients was about 1-year-old. These patients were followed up at least 24 months. RESULTS: Age of presentation ranged from 2 days to 3 months. There were six females (54.55%) and five males (45.45%). All cases presented simple (introral) ranula. Excision ranula with sublingual gland was performed on seven patients (63.64%) while marsupialization was performed on two patients (18.18%) and two patients (18.18%) were aspiration of the mucus of ranula and no recurrence. There were no recurrent lesions in all cases. CONCLUSION: Conservative treatment of infant ranula maybe includes observation for 6 months for spontaneous resolution. The methods for observation is performed the aspiration of mucus and marsupialization. The resection of ipsilateral sublingual gland is recommended if ranula recurred for infant patients about 1-year-old. We believe that it is safe that the submandibular duct and complete sublingual nerve are dissected before the sublingual gland is removed.

[Relationship among expression of vascular endothelial growth factor-C(VEGF-C), angiogenesis, lymphangiogenesis, and lymphatic metastasis in oral cancer].

BACKGROUND & OBJECTIVE: There may be a close relationship among the vascular endothelial growth factor-C (VEGF-C) expression, peritumour lymphatic vessels, and lymph node metastasis. The purpose of this study was to compare the relationship among VEGF-C mRNA expression, density of lymphatic and blood vessels, and lymphatic metastasis in oral squamous carcinoma. METHODS: VEGF-C mRNA was determined by RT-PCR. Lymphatic and blood vessel differential stain was determined by enzyme-histochemical technique. Automated image analysis quantification was applied to determine the number of total lymphatic and blood vessels in unit area (TNa). RESULTS: The peri-tumor lymphatic TNa of oral carcinoma was significantly higher in VEGF-C-positive group than those in VEGF-C-negative group(26.42 +/- 5.85: 17.34 +/- 6.48) (P < 0.01), but the blood TNa was a few higher(35.16 +/- 15.55: 33.49 +/- 13.73) (P > 0.05). Lymphatic TNa (30.67 +/- 5.76: 21.94 +/- 5.84) (P < 0.01) and blood TNa (44.19 +/- 14.29: 30.61 +/- 11.82) (P < 0.01) were significantly higher in lymph node metastasis group than those in no-metastasis group. CONCLUSION: VEGF-C mainly promotes peri-tumor lymphangiogenesis and has a little effect on angiogenesis. Simultaneous increase of lymphatic and blood vessels may be related to the synergic expression of VEGF, VEGF-C and their receptors.