Transcriptome sequencing and metabolome analysis reveal the molecular mechanism of Salvia miltiorrhiza in response to drought stress.

Salvia miltiorrhiza is commonly used as a Chinese herbal medicine to treat different cardiovascular and cerebrovascular illnesses due to its active ingredients. Environmental conditions, especially drought stress, can affect the yield and quality of S. miltiorrhiza. However, moderate drought stress could improve the quality of S. miltiorrhiza without significantly reducing the yield, and the mechanism of this initial drought resistance is still unclear. In our study, transcriptome and metabolome analyses of S. miltiorrhiza under different drought treatment groups (CK, A, B, and C groups) were conducted to reveal the basis for its drought tolerance. We discovered that the leaves of S. miltiorrhiza under different drought treatment groups had no obvious shrinkage, and the malondialdehyde (MDA) contents as well as superoxide dismutase (SOD) and peroxidase (POD) activities dramatically increased, indicating that our drought treatment methods were moderate, and the leaves of S. miltiorrhiza began to initiate drought resistance. The morphology of root tissue had no significant change under different drought treatment groups, and the contents of four tanshinones significantly enhanced. In all, 5213, 6611, and 5241 differentially expressed genes (DEGs) were shared in the A, B, and C groups compared with the CK group, respectively. The results of KEGG and co-expression analysis showed that the DEGs involved in plant-pathogen interactions, the MAPK signaling pathway, phenylpropanoid biosynthesis, flavonoid biosynthesis, and plant hormone signal transduction responded to drought stress and were strongly correlated with tanshinone biosynthesis. Furthermore, the results of metabolism analysis indicated that 67, 72, and 92 differentially accumulated metabolites (DAMs), including fumarate, ferulic acid, xanthohumol, and phytocassanes, which were primarily involved in phenylpropanoid biosynthesis, flavonoid biosynthesis, and diterpenoid biosynthesis pathways, were detected in these groups. These discoveries provide valuable information on the molecular mechanisms by which S. miltiorrhiza responds to drought stress and will facilitate the development of drought-resistant and high-quality S. miltiorrhiza production.

Malignant transformation of biliary adenofibroma combined with benign lymphadenopathy mimicking advanced liver carcinoma: A case report.

BACKGROUND: Biliary adenofibromas (BAFs) are rare primary hepatic neoplasms, some of which can potentially undergo malignant transformation. Here, we describe a rare case of malignant transformation of BAF. CASE SUMMARY: A 51-year-old female was referred to our hospital with epigastric pain. Computed tomography showed a solitary liver mass combined with the enlargement of multiple mediastinal and cervical lymph nodes, clinically mimicking a liver carcinoma with extensive lymph node metastasis. However, core needle biopsy suggested BAF with malignant transformation. Finally, the patient underwent curative resection of the neoplasm and was recurrence-free for 12 mo. CONCLUSION: Our case serves as an example of a rare manifestation of BAF. Our report and the previously published experience, reinforce that curative resection should be considered the primary treatment for BAFs with malignant transformation, leading to a favorable prognosis.

Pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction in the liver of rats with severe acute pancreatitis.

AIM: To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis. METHODS: Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloe-emodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated. RESULTS: The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-α and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P < 0.05), while there was no statistical difference in the MG and HDG. CONCLUSION: DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.

Auricular acupuncture with seed or pellet attachments for primary insomnia: a systematic review and meta-analysis.

BACKGROUND: Primary insomnia is a common health issue in the modern world. We conducted a systematic review of the auricular therapy, aiming to evaluate whether there are advantages of auricular acupuncture with seed or pellet attachments for the treatment of primary insomnia. METHODS: A search of relevant literatures was performed on major medical databases, including Medline, Embase, CENTRAL, CBM, CNKI, VIP, Wanfang Data and so on. Risk of bias evaluation, meta-analysis, sensitivity analysis and evidence rating of all extracted information were conducted also. RESULTS: A total of 1381 records were identified, with 15 studies deemed eligible for the present review. Meta-analyses were conducted in two comparisons separately: participants received auricular acupuncture were more likely to make an improvement in clinical effective rate (RR = 1.40, 95% CI 1.07 to 1.83), sleep duration (MD = 56.46, 95% CI 45.61 to 67.31), sleep efficiency(MD = 12.86, 95% CI 9.67 to 16.06), global score on PSQI (MD = -3.41, 95% CI -3.93 to -2.89), number of awakenings( MD = -3.27, 95% CI -6.30 to -0.25) and sleep onset latency(MD = -10.35, 95% CI -14.37 to -6.33) when compared to sham auricular acupuncture or placebo; while in auricular acupuncture VS medications comparison, a better effective rate (RR = 1.24, 95% CI 1.15 to 1.34), better sleep efficiency(MD = 21.44, 95% CI 16.30 to 26.58), lower PSQI score (MD = -3.62, 95% CI -4.59 to -2.65) and less adverse effect (RR = 0.11, 95% CI 0.04 to 0.26) can be seen also in auricular acupuncture group. Although these results suggested benefits of auricular acupuncture, the overall quality of evidence rated by the GRADE system was low. CONCLUSION: Statistical analyses of the outcomes revealed a positive effect of auricular acupuncture for primary insomnia. Nonetheless, considering the poor methodological quality, insufficient sample size and possible publication bias, current evidence is not yet adequate to provide a strong support for the use of auricular acupuncture in the treatment of primary insomnia. More strictly designed clinical studies will be needed to obtain a more explicit conclusion.

[Auricular acupuncture for primary insomnia: a systematic review based on GRADE system].

The clinical efficacy and safety of auricular acupuncture (AA) for treatment of primary insomnia was evaluated. After a comprehensive retrieval in domestic and foreign databases, literatures were strictly screened and Revman 5.2 software was applied to perform a Meta-analysis on eligible randomized controlled trials (RCTs). The evidence quality was assessed with GRADE profiler 3.6 software. As a result, 8 articles were included involving 894 patients. Compared among AA and sham AA, placebo AA, blank control, there was significant difference in Pittsburgh sleep quality index (PSQI) [WMD = -3.48, 95% CI (-3.96, -3.00)], sleep latency LWMD = -10.14, 95% CI (-17.16, -3.12)] and sleep awakening times [WMD = -9.98, 95% CI (-1.10,-0.48)]. Compared between AA and western medication, there was significant difference in PSQI [WMD = -3.62, 95% CI (-4.59, -2.65)]. The evidence quality was moderate in AA vs. sham AA, placebo AA or blank control, while that of the rest was extremely low. No reports of adverse events were described in all studies. In conclusion, for the treatment of primary insomnia, AA could effectively improve sleep quality, but due to the low evidence quality, cautious attitude should be taken on this conclusion, and clinical trials with large sample and high quality were needed in the further.

Calcitriol inhibits the growth of MHCC97 heptocellular cell lines by down-modulating c-met and ERK expressions.

BACKGROUND: Previous studies have demonstrated that Calcitriol or its analogs has an anti-tumour activity. This study was designed to determine the effect and mechanism of Calcitriol on MHCC-97 heptocellular cell lines. METHODS: MHCC97 cell lines were treated with Calcitriol of 10(-6) approximately 10(-9) M concentration and with Calcitriol in lipiodol ultra-fluid (LUF) respectively. The conditions of cell proliferation were analyzed by MTT method. The cell apoptosis and cycle were analyzed by using a flow cytometer. Hepatocyte growth factor (HGF) concentration in the cell supernatant was measured by using ELISA method. C-met and vitamin D receptor (VDR) mRNA in cells were determined by using RT-PCR method. VDR and ERK(1/2) proteins were determined by using Western Blotting method. RESULTS: Calcitriol inhibited the proliferation of MHCC97 cell lines with an accumulation of cells in the G(0)/G(1) phase and reduction of cells in S phase. Calcitriol dissolved in LUF resulted in a better and longer inhibitive effect on the cell lines than Calcitriol alone. MHCC97 cell lines secreted HGF and expressed c-met mRNA and ERK(1/2) proteins abundantly. Calcitriol remarkably inhibited the expressions of c-met mRNA and ERK(1/2) proteins. CONCLUSION: Calcitriol inhibits the growth of MHCC-97 heptocellular cell lines by down modulating c-met and ERK expressions.

[Study on the prognostic value of hepatocyte growth factor and c-met for patients with hepatocellular carcinoma].

OBJECTIVE: To analyze the prognostic value of hepatocyte growth factor (HGF) and c-met for patients with hepatocellular carcinoma (HCC) after hepatectomy. METHODS: Twenty-five patients undergoing partial hepatectomy for HCC were studied. Serum HGF level was determined using ELISA kit before and after operation respectively. c-met protein and mRNA expression in cancerous and paracancerous tissues were detected by immunohistochemical and RT-PCR methods respectively. The correlations of clinical-pathologic parameters with the HGF level in serum and c-met expression in cancerous tissue were analyzed respectively. RESULTS: HCC patients had a significantly higher concentration of serum HGF than normal controls and chronic hepatitis B respectively [(1.03 +/- 0.09) ng/ml vs (0.69 +/- 0.02) ng/ml and (0.74 +/- 0.09) ng/ml]. No significant difference in serum HGF was observed between HCC and cirrhosis patients with Child-Pugh score B/C [(1.03 +/- 0.09) ng/ml vs (1.04 +/- 0.11) ng/ml]. Serum HGF concentrations were positively correlated with tumor size (> 5 cm), node cirrhosis, portal vein tumor thrombi (PVTT) and preoperative alpha-fetoprotein (AFP) level (> or = 400 microg/L). After the resection of tumor, serum HGF concentration had a peak on the third postoperative day (POD), and then declined, but did not return to normal level on the tenth POD. From preoperative day to third POD, HGF concentration had a higher elevation in patients with major resection than with local resection. Moderately or strongly positive expression of c-met protein was observed in 21 cancerous regions (21/25), and only in 5 paracancerous regions. The intensive expression of c-met mRNA was 100% (25/25) detectable in the cancerous tissues, but only 24% (6/25) in the paracancerous tissues. The expression extent of c-met protein was correlated with portal vein tumor thrombi (PVTT). In paracancerous tissues, the expression of c-met protein was more intense in patients with cirrhosis than those without cirrhosis. The patients with recurrence or metastases after operation had a higher level of serum HGF and more intensive expression of c-met than other patients. No significant association was observed between HGF in serum and c-met expression in cancerous tissue. CONCLUSIONS: The over-expression of HGF and its receptor c-met indicate an adverse prognosis for HCC patients. The sustained high level of serum HGF after hepatectomy may be a factor related to early tumor recurrence and metastasis.

Influence of age and sex on pharmacodynamics of propofol in neurosurgical patients: model development.

AIM: To determine propofol concentration in the cerebral spinal fluid (CSF) of neurosurgical patients and carry out a preliminary population pharmacodynamic study. METHODS: Twenty-seven elective neurosurgical patients (12 men and 15 women) aged 17-74 years received propofol in a bolus dose of 2 mg/kg for 5 min and an infusion of 10 mg/kg per h for 5 min. Frequent CSF samples were drawn and assayed for propofol concentration. The bispectral index (BIS) was used to measure the drug effect. All data were analyzed first with the Excel software package, then pharmacodynamics modeling was performed using the NONMEM software package. RESULTS: The CSF concentration was related to the drug effect with linear and sigmoid Emax models. The parameters for the linear addictive model were a=1.11 and b=95.4. The parameters for the linear exponential model were a=1.05 and b=92.7. The parameters for the sigmoid E(max) model were E(max)=119, EC(50)=53.6 ng/mL, and N=1.51. When the covariates of age, weight and sex were considered, the parameters of models, objective function, the standard error of the mean and the prediction error were not optimized. CONCLUSION: Linear additive, linear exponential and sigmoid E(max) models can be used to describe the pharmacodynamics of propofol with respect to the concentration in CSF. In this small population, age (17-74 years), weight (47-98 kg) and sex did not influence any of the pharmacodynamic parameters of propofol. To verify these preliminary results, a larger study population is required.

Apoptosis induced by preoperative oral 5'-DFUR administration in gastric adenocarcinoma and its mechanism of action.

AIM: To study the apoptosis induced by preoperative oral 5'-DFUR administration in gastric adenocarcinoma and its mechanism of action. METHODS: Sixty gastric cancer patients were divided randomly into three groups (20 each group) before operation: group one:5'-DFUR oral administration at the dose of 800-1200 mg/d for 3 - 5 d, group two: 500 mg 5-FU + 200 mg/d CF by venous drip for 3 - 5 d,group three (control group). One or two days after chemotherapy, the patients were operated. Fas/FasL,PD-ECGF and PCNA were examined by immunohistochemistry and apoptotic tumor cells were detected by in situ TUNEL method. Fifty-four patients received gastrectomy, including 12 palliative resections and 42 radical resections. Six patients were excluded. Finally 18 cases in 5'-DFUR group, 16 cases in CF+5-FU group, and 20 cases in control group were analyzed. RESULTS: There was no significant difference in patient mean age, gender, white blood cell count, haematoglobin (HB),thromboplastin, perioperative complication incidence, radical or palliation resection, invasion depth (T), lymphonode involvement (N),metastasis (M) and TNM staging among the three groups. However,the PCNA index (PI) in 5'-DFUR group (40.51+/-12.62) and 5-FU+CF group (41.12+/-15.26) was significantly lower than that in control group (58.33+/-15.69) (F=9.083, P=0.000). The apoptotic index (AI) in 5'-DFUR group (14.39+/-9.49) and 5-FU+CF group (14.11+/-9.68)was significantly higher than that in control group (6.88+/-7.37) (F=4.409, P=0.017).The expression rates of Fas and FasL in group one and group three were 66.7% (12/18) and 50% (9/18), 43.8% (7/16) and 81.3% (13/16), 45.0% (9/20) and 85% (17/20), respectively. The expression rate of FasL in 5'-DFUR group was significantly lower than that in the other two groups (chi2=6.708, P=0.035). Meanwhile, the expression rate of PD-ECGF was significantly lower in 5'-DFUR group (4/18,28.6%) than in CF+5-FU group(9/16,56.3%)and control group (13/20,65.0%) (chi2=7.542, P=0.023). The frequency of Fas expression was significantly correlated with palliative or radical resection (chi2=7.651, P=0.006), invasion depth (chi2=8.927, P=0.003), lymphatic spread (chi2=4.488, P=0.034) and UICC stages (chi2=8.063, P=0.045) respectively. By the end of March 2005,45 patients were followed up. The 0.5-, 1-, 2-, 3-year survival rates were 96%,73%,60%,48%, respectively, which were related with T, N, M and Fas expression, but not with PD-ECGF and FasL expression. CONCLUSION: Preoperative oral 5'-DFUR administration may induce apoptosis of gastric carcinoma cells and decrease tumor cell proliferation index,but cannot improve the prognosis of patients with gastric cancer.Down-regulation of FasL and PD-ECGF expression mediated by 5'-DFUR may be one of its anti-cancer mechanisms.Fas expression correlates with the progression of gastric carcinoma and may be an effective prognostic factor.

The Chinese classification system compared with TNM staging in prognosis of patients with primary hepatic carcinoma after resection.

BACKGROUND: The life expectancy of a patient with primary hepatic carcinoma (PHC) is hard to predict, and it is related to many prognostic factors. The Chinese classification system including five parameters: tumor, vascular thrombosis, lymph node metastasis, distant metastasis and Child-Pugh stage developed in 1999 was adopted by the 8th National Conference on Liver Cancer of the Chinese Anti-Cancer Association in 2001. In this study, the discriminatory ability of the Chinese classification system was compared with that of the TNM staging in patients for resection of PHC, in addition to the evaluation of prognostic value. METHODS: The data of 246 patients who had undergone resection of PHC from January 1986 to December 2000 (average age, 51 years; male/female ratio, 213/33) were retrospectively studied. Among the 246 patients, 227 were followed up for at least 3 years. RESULTS: The 1-, 3-, 5-, 7-, and 10-year tumor-free survival rates were 55%, 30%, 25%, 20% and 18%, respectively. The Chinese classification system was better than the TNM staging system in predicting survival rate of patients with PHC, as confirmed by survival curves shown by the Kaplain-Meier method. The mean survival time was 155, 70, 39, 16, and 4 months in patients with the Chinese classification stages Ia, Ib, IIa, IIb, and III, respectively. The 1-, 3-, 5-, 7-, and 10-year tumor-free survival rates of the Chinese classification system and TNM staging were statistically significant and had a slightly positive relationship. The predictive capacity of the Chinese classification system was confirmed in any two subgroups of patients undergoing operation. COX proportional hazards regression analysis showed that the Chinese classification system was the only independent prognostic factor for survival. CONCLUSIONS: Taking both tumor extension and liver function into account, we consider that the Chinese classification system making up for the deficiency of UICC TNM staging is more precise in predicting the prognosis of patients with resection of PHC.

Survival factors after resection of small hepatocellular carcinoma.

BACKGROUND: Early resection of hepatocellular carcinoma is a key measure to prolong the survival of patients. This study was designed to summarize our experience in surgical resection of small hepatocellular carcinoma (HCC), and to analyze the factors influencing the postoperative survival of patients. METHODS: The clinicopathologic data of 105 patients with small HCC after resection from 1986 through 2003 were analyzed; the patients had been followed up for more than half a year (median 33 months). Nine clinicopathologic factors, preoperative alpha-fetoprotein (AFP) level, liver cirrhosis, Child-Pugh score, tumor size (>2 cm vs. < or = 2 cm) and number (single vs. multiple), capsule formation, portal vein tumor thrombi (PVTT), Edmondson tumor grade and surgical method, were analyzed by the log-rank test and the Cox proportional harzards model analysis. RESULTS: The cumulative 1-, 3- and 5-year survival rates after the operation were 86.5%, 70.3% and 55.2%, respectively, and the 1-, 3- and 5-year disease-free survival rates were 78%, 58.9% and 45.6%, respectively. One patient died from esophagogastric varices hemorrhage in 2 weeks after reoperation. Thirty-six patients had intrahepatic recurrence or metastasis postoperatively and 34 patients died. The Kaplan-Meier method and the Cox proportional harzards model analysis indicated that poor Child-Pugh score, tumor more than 2 cm in diameter, PVTT and multiple lesions (including satellitic lesions) were adverse factors affecting postoperative survival. The Cox proportional harzards model analysis indicated that tumor size, PVTT and multiple lesions were the factors influencing postoperative disease-free survival. CONCLUSIONS: Limited hepatectomy with a margin more than 1 cm is an appropriate surgical approach. Adverse preoperative Child-Pugh score and postoperative intrahepatic recurrences are the main factors leading to the death of patients with small HCC.

[Prognostic factors influencing postoperative survival in patients with

OBJECTIVE: To summarize the experience of surgical resection, and to analyze the prognostic factors that can influence the postoperative survival in patients with small hepatocellular carcinoma (small HCC) of 2 cm vs.

Malignant gastric carcinoids with liver metastasis.

BACKGROUND: Malignant gastric carcinoids are often accompanied with liver metastasis synchronously or metachronously. Because of the slow growth rate of carcinoids, patients with metastatic tumors can undergo resection for potential cure or for symptom palliation. This study was designed to evaluate the clinicopathologic characteristics and the diagnosis and management of malignant gastric carcinoids. METHODS: Seven patients with malignant gastric carcinoids admitted to our hospital between 1990 and 2002 were followed up and reviewed retrospectively. RESULTS: Liver metastases were found in all the patients, of whom 3 had lesions simultaneously and the other 4 had lesions postoperatively. More than 2 lesions were found in all these patients, except a solitary liver lesion in one. Follow-up showed two patients died within 2 months, three patients in 20, 25 and 32 months after operation respectively, and the other two have been surviving for more than 5 and 3 years respectively. CONCLUSIONS: Malignant gastric carcinoids have a high metastatic tendency to the liver. Surgical treatment in combination with other therapeutic approaches can significantly prolong the survival rate of the patients.