Fangyukangsuan granules ameliorate hyperuricemia and modulate gut microbiota in rats.

Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA.

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

BACKGROUND: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. FINDINGS: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING: A full list of funding bodies that contributed to this study can be found in Acknowledgments section.

The development of a cSMART-based integrated model for hepatocellular carcinoma diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising. METHODS: Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes. RESULTS: An integrated diagnostic model called "Combined method" was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.

The Landscape of Cell-Free HBV Integrations and Mutations in Cirrhosis and Hepatocellular Carcinoma Patients.

PURPOSE: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful noninvasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear. EXPERIMENTAL DESIGN: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. Patients with HCC (n = 481) and liver cirrhosis (LC; n = 517) were recruited in the study. RESULTS: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was first generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR > 1) was identified as a potential HCC-related mutational hot zone. CONCLUSIONS: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of noninvasive detection of virus insertion/mutation.

Complete mitogenomic and phylogenetic characteristics of the speckled wood-pigeon (Columba hodgsonii).

The speckled wood-pigeon, Columba hodgsonii, is mainly distributed in Bhutan, China, India, Laos, Myanmar, Nepal, Pakistan, and Thailand. Although there are several studies on birds in the family Columbidae, no study has focused on C. hodgsonii, a member of this family. Therefore, this study aimed to clarify the phylogenetic status of C. hodgsonii. The complete mitochondrial genome (mitogenome) of C. hodgsonii was sequenced and characterized and compared with those of other Columba species. The C. hodgsonii mitogenome was found to be 17,477 bp in size and contained 13 PCGs, two rRNAs, 22 tRNAs, and one CR. Of the 37 genes encoded by the C. hodgsonii mitogenome, 28 were on the heavy strand and nine were on the light strand. Twelve PCGs were initiated by ATN codons and one PCG harbored an incomplete termination codon (T-). The base composition of C. hodgsonii PCGs was A = 29.44%, T = 24.37%, G = 12.43%, and C = 33.76%. For the whole mitogenome, including PCGs, rRNAs, tRNAs, and the control region, the AT-skew was positive, and the GC-skew was negative. Phylogenetic analysis based on the base sequences of 13 PCGs from 28 Columbidae species and one outgroup using maximum likelihood and Bayesian inference indicated that C. hodgsonii belongs to the genus Columba and that the family Columbidae is monophyletic.

The expression of VEGF-C, VEGFR-3 and its predictive value on lymph node metastasis and prognosis of gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>s To investigate the relationship between the expression of VEGF-C, VEGFR-3 and lymph node metastasis (LNM) in the gastric cancer, and explore the role of VEGF-C, VEGFR-3 in the prognosis of gastric cancer.</p><p><b>METHODS</b>Gastric cancer specimens were selected from gastric cancer database from April, 1994 to December, 2003, which were registered and followed up. The specimens were divided into two groups according to LNM existing or not. Immunohistochemistry staining was performed with anti-VEGF-C, anti-VEGFR-3 monoclonal antibody by DAB method. Their effects on prognosis of gastric cancer patients were analyzed by Kaplan-meier, Logistic and Cox Regression methods.</p><p><b>RESULTS</b>In 188 cases of gastric cancer patients, 97 patients presented with LNM and the rest did not. The positive expression rate of VEGF-C, VEGFR-3 in the group without LNM was lower than those in group with LNM, and there was significant difference between the two groups. There was significant difference in the average lymphatic vessel density between the group with LNM and the group without, and the same results were found between the group with positive VEGF-C expression and the group without.</p><p><b>CONCLUSIONS</b>VEGF-C, VEGFR-3 are over-expressed in gastric cancer patients with LNM, and the expression of VEGF-C, VEGFR-3 are important predictors for the prognosis of gastric cancer.</p>

Related factors and prognosis of hepatic metastasis and peritoneal dissemination in gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the related factors and prognosis of peritoneal dissemination and hepatic metastasis in gastric cancer, and the impact of palliative surgery on the prognosis.</p><p><b>METHODS</b>The clinicopathologic and follow-up data of the patients with gastric carcinoma treated in our hospital from Aug. 1994 to Jul. 2005 were analyzed retrospectively.</p><p><b>RESULTS</b>The clinicopathologic factors correlated with peritoneal dissemination included serosal penetration, whole stomach cancer, undifferentiated type, female and hepatic metastasis, while those correlated with hepatic metastasis included Borrmann IV, lymph node metastasis and peritoneal dissemination (P< 0.05). The postoperative one-year survival rate of the patients with hepatic metastasis (H group) were lower than that of the patients with peritoneal dissemination (P group)(P< 0.05). The one- year survival rate of the patients with peritoneal dissemination undergoing palliative resection was significantly higher than that of the patients undergoing by-pass operation or feeding neostomy, and exploratory laparotomy (P< 0.05), while there was no significant difference among the three groups of the patients with hepatic metastasis.</p><p><b>CONCLUSIONS</b>The short-term prognosis of the patients with hepatic metastasis is poorer than that of the patients with peritoneal dissemination. Palliative resection could improve the short-term survival rate of the patients with peritoneal dissemination, while it had no significant impact on the survival rate of the patients with hepatic metastasis.</p>

Disciplinarian of lymph node metastasis and effect of paraaortic lymph nodes dissection on clinical outcomes in advanced gastric carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the disciplinarian of lymph node metastasis and evaluate the effect of paraaortic lymph nodes dissection on the clinical outcomes in advanced gastric carcinoma.</p><p><b>METHODS</b>One hundred and twenty-six patients who underwent D(3) (including D(3)(+)) radical resection (group D(3)) and 146 patients who underwent D(2) radical resection by the same surgical team (group D(2)) for advanced gastric cancer were enrolled in the present study. The dissected lymph nodes were grouped according to the definition of Japanese Research Society for the Study of Gastric Cancer (JRSGC) (Edition 13th). The lymph node metastasis was analyzed in group D(3). The clinicopathological characteristics and clinical outcomes were compared between the two groups.</p><p><b>RESULTS</b>There were no differences in age, sex, tumor location, Borrman type, histological type and TNM stage between group D(2) and group D(3) (P > 0.05). The No16 lymph node metastatic rate was 3.8%, 22.3%, 46.8% and 32.1% in T(1), T(2), T(3), T(4) stage tumors respectively, 16.3% and 69.5% in the patients with negative and positive serosal invasion respectively; there were no differences in operative mortality (2/126 vs 2/146) and surgical complications (4/126 vs 6/146) between group D(2) and group D(3) (P > 0.05). The 5-year survival rate was 66.5% in group D(3) and 40.2% in group D(2) (P< 0.01). The 5-year survival rates of the patients with I, II, IIIa, IIIb and IV stage tumors who were No16 lymph nodes negative were 94.8%, 95.6%, 72.1%, 58.6%, 59% respectively in group D(3), and 42%, 36%, 27%, 35.6%, 16.3% respectively in group D(2). The 5-year survival rate of the patients with No16 (+) lymph nodes less than 3 was higher than that of the patients with No16(+) lymph nodes more than 3.</p><p><b>CONCLUSIONS</b>No16a2 and No16b1 are the common locations of lymph node metastasis in advanced gastric cancer. The paraaortic lymph node metastasis closely is related with the depth of tumor invasion and serosal invasion. Paraaortic lymph nodes dissection (D(3) or D(3)(+) radical resection) improves the 5-year survival rate of the patients with No16 (-) and No16 (+) lymph nodes less than 3.</p>

Analysis of long-term results of radical gastrectomy combining splenectomy for gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the influence of radical excision combining splenectomy on prognosis of the patients with gastric cancer.</p><p><b>METHODS</b>Between June 1994 and March 2004, 692 patients were operated on for gastric cancer and registered into gastric cancer database. Radical excision (D2, D3 or D4) combining splenectomy for gastric cancer was performed in 45 cases. 343 cases were selected simultaneously for comparison according to the resembling rules in sex, age, tumor size, location, serosa invasion, Borrmann type and range of lymph node dissection. Clinicopathological factors affecting lymph node metastasis, patterns of lymph node metastasis, 5-year survival rate after radical excision combined with splenectomy for gastric cancer were compared.</p><p><b>RESULTS</b>Lymph node metastasis rate of splenic hilus was 15.6 percent. Among them, upper, middle and lower domain is 11.5 percent, 33.3 percent and zero respectively. It was significantly different between gastric adenocarcinoma in proximal and body of stomach and that in distal stomach, poor differentiation and adenocarcinoma anaplastic and well and moderately differentiation adenocarcinoma, Borrmann III and IV types and Borrmann I and II types, infiltrated depth in T(3) and T(4) and infiltrated depth in T(1) and T(2), clinical stages III and IV and clinical stages I and II. The average and median survival time between radical gastrectomy only and radical gastrectomy combining splenectomy for gastric cancer at stage I and II patients were significantly different, but at stage III and IV patients not significantly different.</p><p><b>CONCLUSIONS</b>Spleen should be reserved for patients with gastric cancer at stage I and II, and radical excision combining splenectomy could only be performed at stage III and IV patients with cancer infiltrating body and tail of the pancreas, or lymph nodes metastasis in the splenic hilus. Indication of radical excision combining splenectomy for gastric cancer must be further study to clarify its efficacy.</p>

Surgical treatment and prognosis analysis for patients with gastric cancer infiltrating esophagus / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the reasonable operative approaches,rang e of lymph node dissection and prognostic factors for patients with gastric cancer infiltrating esophagus.</p><p><b>METHODS</b>Six hundred and ninety-three patients were treated surgically for gastric cancer from August 1994 to February 2004. Clinica l data of 63 cases with esophagus invasion were reviewed retrospectively. The range of lymph node metastasis rounding stomach and lymph node metastasis rates were analyzed. The survival rate was compared between the patients with operation performed through upper abdomen median incision and the patients through combined left thoracotomy and abdomen incision. Different factors influencing survival rates were analyzed.</p><p><b>RESULTS</b>Radical resection rate was 85.7%, combined viscera excision was performed in 25 cases (39.7%). The overall rate of lymph node metastasis was 73.0%, and lymph node metastasis rate involving abdominal cavity and thoracic cavity was 73.0% and 12.7% respectively. Upper abdomen median incision was applied in 35 cases with 18% of 5-year survival rate, while combined left thoracotomy and abdomen incision was performed in 28 cases with 38% of 5-year survival rate. There was a significant difference in 5-year survival rate between the two groups (P< 0.05). The survival rate was 16% in combined viscera excision group. Logistic analysis revealed that age, histologic type, tumor diameter, Borrmann type, lymph node metastasis, lymph node metastasis involving thoracic cavity and operative approach were important factors influencing postoperative survival rate.</p><p><b>CONCLUSION</b>Radical resection of gastric cancer infiltrating esophagus ought to include dissection of upper abdominal cavity, lower thoracic cavity and para-midkiff lymph nodes. Combined left thoracotomy and abdomen incision may improve the efficacy of radical resection and postoperative 5-year survival rate for patients with gastric cancer infiltrating oesophagus.</p>

Effectiveness of para-aortic lymph node dissection for advanced gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To assess whether any correlation exists between survival and the extent of lymph-node dissection.</p><p><b>METHODS</b>D(2), D(2)(+) or D(3) radical resection was performed on 158 patients with advanced gastric cancer. Among them, 73 were subjected to para-aortic lymph node dissection, (PALD group), and the other 85 were not subjected to the operation (non-PALD group). There was no significant difference in age, gender, site of tumors, type of Borrmann and histology between the two groups. The PALD group showed more advanced diseases in term of tumor invasion, lymph node metastasis and clinicopathological stage.</p><p><b>RESULTS</b>Average operation time was longer in the PALD group than in the non-PALD group [(280 +/- 93) min VS. (245 +/- 91) min, (P < 0.01)]. Blood transfusion volume was (693 +/- 324) ml in the PALD group, and (460 +/- 375) ml in the non-PALD group (P < 0.01). No anastomotic leaks, pancreatic fistula, abdominal abscess and ileus were observed in both groups. No significant complications were found except for a higher incidence of diarrhea in the PALD group. Significant difference was found in survival curve, mean and median survival time between the two groups. The difference in survival was also found between patients with positive and negative lymph node metastasis in the PALD and non-PALD groups. Again, there was significant difference in survival between positive and negative No. 16 lymph node in the PALD group.</p><p><b>CONCLUSION</b>Para-aortic lymph node dissection offers a significant survival benefit to curable patients with advanced gastric cancer. It is similar to limited lymphadenectomy in morbidity and mortality.</p>