Risk factor analysis and a new prediction model of venous thromboembolism after pancreaticoduodenectomy.

AIM: The present study aimed to identify risk factors for venous thromboembolism (VTE) after pancreaticoduodenectomy (PD) and to develop and internally validate a predictive model for the risk of venous thrombosis. METHODS: We retrospectively collected data from 352 patients who visited our hospital to undergo PD from January 2018 to March 2022. The number of patients recruited was divided in an 8:2 ratio by using the random split method, with 80% of the patients serving as the training set and 20% as the validation set. The least absolute shrinkage and selection operator (Lasso) regression model was used to optimize feature selection for the VTE risk model. Multivariate logistic regression analysis was used to construct a prediction model by incorporating the features selected in the Lasso model. C-index, receiver operating characteristic curve, calibration plot, and decision curve were used to assess the accuracy of the model, to calibrate the model, and to determine the clinical usefulness of the model. Finally, we evaluated the prediction model for internal validation. RESULTS: The predictors included in the prediction nomogram were sex, age, gastrointestinal symptoms, hypertension, diabetes, operative method, intraoperative bleeding, blood transfusion, neutrophil count, prothrombin time (PT), activated partial thromboplastin time (APTT), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AST/ALT), and total bilirubin (TBIL). The model showed good discrimination with a C-index of 0.827, had good consistency based on the calibration curve, and had an area under the ROC curve value of 0.822 (P < 0.001, 95%confidence interval:0.761-0.882). A high C-index value of 0.894 was reached in internal validation. Decision curve analysis showed that the VTE nomogram was clinically useful when intervention was decided at the VTE possibility threshold of 10%. CONCLUSION: The novel model developed in this study is highly targeted and enables personalized assessment of VTE occurrence in patients who undergo PD. The predictors are easily accessible and facilitate the assessment of patients by clinical practitioners.

Inhibition of drug-metabolizing enzymes by Jingyin granules: implications of herb-drug interactions in antiviral therapy.

Jingyin granules, a marketed antiviral herbal medicine, have been recommended for treating H1N1 influenza A virus infection and Coronavirus disease 2019 (COVID-19) in China. To fight viral diseases in a more efficient way, Jingyin granules are frequently co-administered in clinical settings with a variety of therapeutic agents, including antiviral drugs, anti-inflammatory drugs, and other Western medicines. However, it is unclear whether Jingyin granules modulate the pharmacokinetics of Western drugs or trigger clinically significant herb-drug interactions. This study aims to assess the inhibitory potency of the herbal extract of Jingyin granules (HEJG) against human drug-metabolizing enzymes and to clarify whether HEJG can modulate the pharmacokinetic profiles of Western drug(s) in vivo. The results clearly demonstrated that HEJG dose-dependently inhibited human CES1A, CES2A, CYPs1A, 2A6, 2C8, 2C9, 2D6, and 2E1; this herbal medicine also time- and NADPH-dependently inhibited human CYP2C19 and CYP3A. In vivo tests showed that HEJG significantly increased the plasma exposure of lopinavir (a CYP3A-substrate drug) by 2.43-fold and strongly prolonged its half-life by 1.91-fold when HEJG (3 g/kg) was co-administered with lopinavir to rats. Further investigation revealed licochalcone A, licochalcone B, licochalcone C and echinatin in Radix Glycyrrhizae, as well as quercetin and kaempferol in Folium Llicis Purpureae, to be time-dependent CYP3A inhibitors. Collectively, our findings reveal that HEJG modulates the pharmacokinetics of CYP substrate-drug(s) by inactivating CYP3A, providing key information for both clinicians and patients to use herb-drug combinations for antiviral therapy in a scientific and reasonable way.

Facile Benzylic Alkylation of Arenes with Alcohols by Catalysis with Spirocyclic NHC IrIII Pincer Complex.

A facile benzylic alkylation of indenes and other arenes was developed from readily available primary and secondary alcohols using our newly investigated CCC pincer IrIII catalyst (SNIr-H). Excellent regioselectivity and yield (89 %) of the C3-alkylated indenes were obtained. Additionally, the challenging sp2 C-alkylation was readily accomplished. This method could be utilized for the synthesis of the analogs of a histamine H1 receptor antagonist and the functional material template molecule, indeno[2,1-a]indene. A hemilabile IrIII -dihydride intermediate was proposed based on control experiments and previous density functional theory (DFT) calculations for the borrowing hydrogen mechanism and is key to the success of this IrIII catalyst in the reduction of unactivated multi-substituted olefin intermediates.

Laparoscopic versus open pancreatic resection for ductal adenocarcinoma: separate propensity score matching analyses of distal pancreatectomy and pancreaticoduodenectomy.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a leading causes of cancer mortality worldwide. Currently, laparoscopic pancreatic resection (LPR) is extensively applied to treat benign and low-grade diseases related to the pancreas. The viability and safety of LPR for PDAC needs to be understood better. Laparoscopic distal pancreatectomy (LDP) and pancreaticoduodenectomy (LPD) are the two main surgical approaches for PDAC. We performed separate propensity score matching (PSM) analyses to assess the surgical and oncological outcomes of LPR for PDAC by comparing LDP with open distal pancreatectomy (ODP) as well as LPD with open pancreaticoduodenectomy (OPD). METHODS: We assessed the data of patients who underwent distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) for PDAC between January 2004 and February 2020 at our hospital. A one-to-one PSM was applied to prevent selection bias by accounting for factors such as age, sex, body mass index, and tumour size. The DP group included 86 LDP patients and 86 ODP patients, whereas the PD group included 101 LPD patients and 101 OPD patients. Baseline characteristics, intraoperative effects, postoperative recovery, and survival outcomes were compared. RESULTS: Compared to ODP, LDP was associated with shorter operative time, lesser blood loss, and similar overall morbidity. Of the 101 patients who underwent LPD, 10 patients (9.9%) required conversion to laparotomy. The short-term surgical advantage of LPD is not as apparent as that of LDP due to conversions. Compared with OPD, LPD was associated with longer operative time, lesser blood loss, and similar overall morbidity. For oncological and survival outcomes, there were no significant differences in tumour size, R0 resection rate, and tumour stage in both the DP and PD subgroups. However, laparoscopic procedures appear to have an advantage over open surgery in terms of retrieved lymph nodes (DP subgroup: 14.4 ± 5.2 vs. 11.7 ± 5.1, p = 0.03; PD subgroup 21.9 ± 6.6 vs. 18.9 ± 5.4, p = 0.07). These two groups did not show a significant difference in the pattern of recurrence and overall survival rate. CONCLUSIONS: Laparoscopic DP and PD are feasible and oncologically safe procedures for PDAC, with similar postoperative outcomes and long-term survival among patients who underwent open surgery.

Development of a novel anti-liver fibrosis formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis.

CONTEXT: Xiaoyaosan decoction (XYS), a classical Traditional Chinese Medicine (TCM) formula is used to treat liver fibrosis in clinics. OBJECTIVE: This study explores defined compound combinations from XYS decoction to treat liver fibrosis. MATERIALS AND METHODS: Network pharmacology combined with transcriptomics analysis was used to analyze the XYS decoction and liver depression and spleen deficiency syndrome liver fibrosis. From the constructed XYS-Syndrome-liver fibrosis network, the top 10 active formulas were developed by topological analysis according to network stability. The most active formula was determined by in vitro study. The anti-fibrosis effect was evaluated by in vitro and in vivo studies. RESULTS: According to the network XYS-Syndrome-liver fibrosis network, 8 key compounds and 255 combinations were predicted from in XYS. Luteolin, licochalcone A, aloe-emodin and acacetin formula (LLAAF) had a synergistic effect on the proliferation inhibition of hepatic stellate cells compared to individual compounds alone. The treatment of XYS and LLAAF showed a similar anti-liver fibrotic effect that reduced histopathological changes of liver fibrosis, Hyp content and levels of α-SMA and collagen I in CCl4-induced liver fibrosis in rats. Transcriptomics analysis revealed LLAAF regulated PI3K-Akt, AMPK, FoxO, Jak-STAT3, P53, cell cycle, focal adhesion, and PPAR signalling. Furthermore, LLAAF was confirmed to regulate Jak-STAT and PI3K-Akt-FoxO signalling in vitro and in vivo. CONCLUSIONS: This study developed a novel anti-liver formula LLAAF from XYS, and demonstrated its anti-liver fibrotic activity which may be involved in the regulation of Jak-STAT and PI3K-Akt-FoxO signalling.

Surgical outcomes of laparoscopic distal pancreatectomy in elderly and octogenarian patients: a single-center, comparative study.

BACKGROUND: Although recent reports have suggested the advantages of laparoscopic distal pancreatectomy (LDP), the potential benefits of this approach in elderly patients remain unclear. The aim of this study was to clarify the value of LDP in the elderly, in whom co-morbid diseases were generally more common. METHODS: Seventy elderly patients (≥ 70 years) and 264 non-elderly patients (40-69 years) who underwent LDP, and 48 elderly patients (≥ 70 years) who underwent open distal pancreatectomy (ODP) between May 2005 and May 2018 were studied. Demographics, intraoperative, and postoperative outcomes were compared. RESULTS: Comorbidity was more common in elderly patients than in non-elderly patients who underwent LDP (57.1 vs. 38.3%, p < 0.01). The intraoperative factors, postoperative complication rate, and length of hospital stay were comparable in these two groups. Elderly patients who underwent LDP had a significantly shorter operative time (185.5 vs. 208.0 min, p = 0.02), less blood loss (191.0 vs. 291.8 mL, p < 0.01), and reduced length of postoperative hospital stay (11.4 vs. 15.1 days, p < 0.01) than elderly patients who had ODP. The overall complication rate tended to be lower in LDP group than that in ODP group (20.0 vs. 33.3%, p = 0.07). CONCLUSION: LDP performed on the elderly is safe and feasible, leading to short-term outcomes similar to those of non-elderly patients. LDP could be an alternative to ODP in elderly patients, providing a lower rate of morbidity and favorable postoperative recovery and outcomes.

Resveratrol Inhibits the Migration and Metastasis of MDA-MB-231 Human Breast Cancer by Reversing TGF-ß1-Induced Epithelial-Mesenchymal Transition.

Metastasis is a major cause of death in patients with breast cancer. In the process of cancer development, epithelial-mesenchymal transition (EMT) is crucial to promoting the invasion and migration of tumor cells. In a previous study, the role of resveratrol in migration and metastasis was investigated in MDA-MB-231 (MDA231) human breast cancer cells and a xenograft-bearing mouse model. Additionally, the related mechanism was explored. In the present study, in vitro Transwell assays showed that resveratrol can inhibit the migration of transforming growth factor (TGF)-ß1-induced MDA231 cells in a concentration-dependent manner. An enzyme-linked immunosorbent assay (ELISA) showed that resveratrol can reduce the secretion of matrix metalloproteinase (MMP)-2 and MMP-9. Immunofluorescence was performed to confirm the expression of EMT-related markers. Immunofluorescence assays confirmed that resveratrol changed the expression of the EMT-related markers E-cadherin and vimentin. Western blot analysis demonstrated that resveratrol decreased the expression levels of MMP-2, MMP-9, Fibronectin, α-SMA, P-PI3K, P-AKT, Smad2, Smad3, P-Smad2, P-Smad3, vimentin, Snail1, and Slug, as well as increased the expression levels of E-cadherin in MDA231 cells. In vivo, resveratrol inhibited lung metastasis in a mouse model bearing MDA231 human breast cancer xenografts without marked changes in body weight or liver and kidney function. These results indicate that resveratrol inhibits the migration of MDA231 cells by reversing TGF-ß1-induced EMT and inhibits the lung metastasis of MDA231 human breast cancer in a xenograft-bearing mouse model.

A metabolic mechanism analysis of Fuzheng-Huayu formula for improving liver cirrhosis with traditional Chinese medicine syndromes.

Fuzheng-Huayu formula (FZHY), a Chinese herbal mixture prescription, has been proven effective in treating liver fibrosis and cirrhosis in both clinical trials and animal experiments. In this study we assessed the metabolic mechanisms of traditional Chinese medicine (TCM) syndrome-based FZHY treatment in liver cirrhosis (LC). A total of 113 participants, including 50 healthy controls and 63 LC patients, were recruited. According to the diagnosis and differentiation of the TCM syndromes, the LC patients were classified into 5 TCM syndrome groups including the liver stagnation syndrome (LSS), spleen deficiency and damp overabundance syndrome (SDDOS), damp-heat accumulation syndrome (DHAS), liver-kidney Yin deficiency syndrome (LKYDS), and blood stagnation syndrome (BSS), and administered FZHY for 6 months. FZHY treatment significantly decreased serum levels of hyaluronic acid (HA), a biochemical marker for LC, as well as TCM syndrome scores (the TCM syndrome scores were decreased in all the groups with significant decreases in the LSS and LKYDS groups). Furthermore, FZHY treatment gradually shifted the metabolic profiles of LC patients from a pathologic state to a healthy state, especially in LC patients with LSS and LKYDS. Twenty-two differently altered metabolites (DAMs) were identified, including carbohydrates, amino acids, fatty acids, etc with 9 DAMs in LSS patients, 9 in LKYDS patients, and 4 in other patients. The metabolic pathways involved in the conversion of amino acids and the body's detoxification process were regulated first, followed by the pathways involved in the body's energy supply process. In conclusion, the evaluation of the effect of TCM syndrome-based FZHY treatment show that FZHY has a better effect on LKYDS and LSS than on the other TCM syndromes, and the metabolic mechanisms might be involved in the increased detoxification function in LKYDS and the improvement of energy supply in LSS, which provides important evidence for the clinical application of TCM syndrome-based treatment.

Chinese herbal formula Fuzheng Huayu alleviates CCl4-induced liver fibrosis in rats: a transcriptomic and proteomic analysis.

Liver fibrosis is a consequence of chronic liver disease that can progress to liver cirrhosis or even hepatocarcinoma. Fuzheng Huayu (FZHY), a Chinese herbal formula, has been shown to exert anti-fibrotic effects. To better understand the molecular mechanisms underlying the anti-fibrotic effects of FZHY, we analyzed transcriptomic and proteomic combination profiles in CCl4-induced liver fibrosis in rats, which were treated with extracted FZHY powder (0.35 g·kg-1·d-1, ig) for 3 weeks. We showed that FZHY administration significantly improved liver function, alleviated hepatic inflammatory and fibrotic changes, and decreased the hydroxyproline content in the livers of CCl4-treated rats. When their liver tissues were examined using microarray and iTRAQ, we found 255 differentially expressed genes (fold change ≥1.5, P<0.05) and 499 differentially expressed proteins (fold change ≥1.2, P<0.05) in the FZHY and model groups. Functional annotation with DAVID (The Database for Annotation, Visualization and Integrated Discovery) showed that 15 enriched gene ontology terms, including drug metabolic process, response to extracellular stimulus, response to vitamins, arachidonic acid metabolic process, response to wounding, and oxidation reduction might be involved in the anti-fibrotic effects of FZHY; whereas KEGG pathway analysis revealed that eight enriched pathways, including arachidonic acid metabolism, retinol metabolism, metabolism of xenobiotics by cytochrome P450, and drug metabolism might also be involved. Moreover, the protein-protein interaction network demonstrated that 10 core genes/proteins overlapped, with Ugt2a3, Cyp2b1 and Cyp3a18 in retinol metabolism pathway overlapped to a higher degree. Compared to the model rats, the livers of FZHY-treated rats had significantly higher mRNA and protein expression levels of Ugt2a3, Cyp2b1 and Cyp3a18. Furthermore, the concentration of retinoic acid was significantly higher in the FZHY-treated rats compared with the model rats. The results suggest that the anti-fibrotic effects of FZHY emerge through multiple targets, multiple functions, and multiple pathways, including FZHY-regulated retinol metabolism, xenobiotic metabolism by cytochrome P450, and drug metabolism through up-regulated Ugt2a3, Cyp2b1, and Cyp3a18. These genes may play important anti-fibrotic roles in FZHY-treated rats.

Short-term outcomes of laparoscopic total gastrectomy for gastric cancer: a comparative study with laparoscopic distal gastrectomy at a high-volume center.

BACKGROUND: Laparoscopic distal gastrectomy (LDG) for gastric cancer has gradually gained popularity. However, laparoscopic total gastrectomy (LTG) has been reported rarely when compared with LDG. This study was designed to evaluate the surgical outcomes as well as the morbidity and mortality of LTG compared with LDG to confirm the feasibility and safety of LTG. MATERIAL AND METHODS: We reviewed the data of patients at our institution undergoing LTG (n = 448) or LDG (n = 956) for gastric cancer between January 2008 and July 2016. Then the clinical characteristics and perioperative clinical outcomes of the two groups were compared. RESULTS: Except for tumor size and stage, there were no statistically significant differences in the clinicopathological parameters between the groups. LTG was associated with significantly longer operation time, late time to postoperative diet, and longer hospital stay compared with the LDG group. Overall complications developed in 60 patients (13.4%) and surgical complications in 48 patients (10.7%) after LTG. Postoperative complications were less frequent in the LDG group than in the LTG group (8.4% versus 13.4%, p < .01), and fewer surgical complications were observed with LDG than with LTG (7.5% versus 10.7%, p = .05). CONCLUSIONS: The results of LTG were favorable even though are not inferior to those of LDG. LTG for gastric cancer is technically feasible and safe. However, because of the limits of this study, other high-quality studies are needed for further evaluation.

Curcumin reduces mitomycin C resistance in breast cancer stem cells by regulating Bcl-2 family-mediated apoptosis.

BACKGROUND: Curcumin, a natural compound derived from the turmeric rhizome Curcuma longa Linn, has anticancer and chemoresistance reduction biological activities. We evaluated the efficacy of curcumin in sensitizing chemotherapy drugs through regulation of Bcl-2-mediated apoptosis in breast cancer stem-like cells (BCSCs). METHODS: Cell survival was measured using MTT assay. Apoptosis-related proteins were observed using western blot analysis. Apoptosis was detected with flow cytometric analysis and by Hoechst 33258 staining. The mitochondrial membrane potential was observed with flow cytometric analysis. RESULTS: The ability of BCSCs to propagate decreased gradually along the passages and was completely lost at the fifth passage [0.1 µmol/L mitomycin C (MMC) with 5 µmol/L curcumin in MCF-7 and 0.5 µmol/L MMC with 5 µmol/L curcumin in MDA-MB-231 cells]. Curcumin combined with MMC treatment significantly decreased the levels of antiapoptotic Bcl-2 and Bcl-w expression, increased the levels of proapoptotic Bax, Bak, Bad, Bik, and Bim expression, and activated caspase-3 and caspase-9 in MCF-7 BCSCs. In the presence of Bcl-2 siRNA, the apoptosis rate increased by 15% in cells treated with curcumin and MMC. The mitochondrial membrane potential decreased by approximately 20% in MCF-7 BCSCs undergoing the combination treatment of curcumin and MMC. The combination-induced decrease in Bcl-2 was regulated by the presence of the Wnt-specific inhibitor PFK115-584 and PI3k inhibitor LY294002. CONCLUSIONS: Our study indicates that curcumin might represent a novel therapeutic agent for treating breast cancer chemoresistance induced by MMC.

Laparoscopic gastrectomy in obese gastric cancer patients: a comparative study with non-obese patients and evaluation of difference in laparoscopic methods.

BACKGROUND: Obesity is a growing epidemic around the world, and obese patients are generally regarded as high risk for surgery compared with normal weight patients. The purpose of this study was to evaluate the influence of obesity on the surgical outcomes of laparoscopic gastrectomy (LG) for gastric cancer. METHODS: We reviewed data for all patients undergoing LG for gastric cancer at our institute between October 2004 and December 2016. Patients were divided into non-obese and obese groups and the perioperative outcomes were compared. Furthermore, a subgroup analysis was conducted to evaluate which of the two commonly used methods of LG, laparoscopic-assisted gastrectomy (LAG) and totally laparoscopic gastrectomy (TLG), is more suitable for obese patients. RESULTS: A total of 1691 patients, 1255 non-obese and 436 obese or overweight patients, underwent LG during the study period. The mean operation time was significantly longer in the obese group than in the non-obese group (209.9 ± 29.7 vs. 227.2 ± 25.7 min, P < 0.01), and intraoperative blood loss was significantly lower in the non-obese group (113.4 ± 34.1 vs. 136.9 ± 36.7 ml, P < 0.01). Time to first flatus, time to oral intake, and postoperative hospital stay were significantly shorter in the non-obese group than in the obese group (3.3 ± 0.8 vs. 3.6 ± 0.9 days; 4.3 ± 1.0 vs. 4.6 ± 1.0 days; and 9.0 ± 2.2 vs. 9.6 ± 2.2 days, respectively; P < 0.01). 119 (9.5%) of the non-obese patients had postoperative complications as compared to 44 (10.1%) of the obese patients (P = 0.71). In the subgroup analysis of all patients, TLG showed improved results for early surgical outcomes compared to LAG, mainly due to its advantages in obese patients. CONCLUSIONS: Obesity is associated with long operation time, increased blood loss, and slow recovery after laparoscopic gastric resection but does not affect intraoperative security or effectiveness. TLG may have less negative results in obese patients than LAG due to a variety of reasons. Our analysis shows that TLG is more advantageous, with regard to early surgical outcomes, for obese patients.

[Single-incision laparoscopic surgery with self-made port for totally extraperitoneal hernioplasty: a report of 7 cases].

OBJECTIVE: To explore the feasibility of single-incision laparoscopic totally extraperitoneal hernioplasty (SILS-TEP) with self-made port for repairing of inguinal hernia. METHODS: SILS-TEP was performed in 7 inguinal hernia patients (9 sides) with conventional laparoscopic instruments and self-made port, which composed of a wound retractor, surgical gloves and 3 ordinary trocars. The clinical data and follow-up results of 7 cases were retrospectively collected and analyzed. RESULTS: The self-made port was applied for SILS-TEP uneventfully without the need of additional ports in all 7 patients (9 inguinal hernias). The median operating time was 90. 0 (70-125) min, intraoperative blood loss was 10. 0 (5. 0-20. 0) mL and postoperative hospital stay was 2.0 (2. 0-4. 0) d. The median pain scores of visual analog scale (VAS) at 6 h,12 h, 24 h and 14 d were 3(2~4), 2(1~2), 1(0~2) and 0(0~1), respectively. There were no intraoperative complications reported, and all patients were satisfied with wound healing. No hernia recurrence was observed during the 3-months of follow-up. CONCLUSION: Our initial experiences show that SILS-TEP with self-made port is a safe and feasible surgery, which can simplify the procedure with available equipments and reduce the cost, therefore can be applied in grass-root hospitals.

Laparoscopic versus open resection for gastric gastrointestinal stromal tumors: an updated systematic review and meta-analysis.

BACKGROUND: In past decades, laparoscopic surgery has been introduced for the treatment of gastrointestinal stromal tumors (GISTs). Recently, additional studies comparing laparoscopic versus open surgery for gastric GISTs have been published, and an updated meta-analysis of this subject is necessary. METHODS: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. Comparative studies of laparoscopic and open surgery for gastric GISTs published before June 2014 were identified from databases. The Newcastle-Ottawa Quality Assessment Scale was used to perform quality assessment and original data were extracted. The statistical software STATA (version 12.0) was used for the meta-analysis. RESULTS: Finally, 22 studies, including a total of 1,166 cases, meet the inclusion criteria for meta-analysis. The operation time was similar between laparoscopic and open surgery. Compared to open surgery, laparoscopic resection was associated withless blood loss (WMD = -58.91 ml; 95% CI, -84.60 to -33.22 ml; P <0.01); earlier time to flatus (WMD = -1.31 d; 95% CI, -1.56 to -1.06, P <0.01) and oral diet (WMD = -1.75 d; 95% CI, -2.12 to -1.39; P <0.01); shorter hospital stay (WMD = -3.68 d; 95% CI, -4.47 to -2.88; P <0.01); and decreased overall complications (relative risk = 0.57; 95% CI, 0.37 to 0.89; P = 0.01). For long-term outcomes, there were no significant differences between two surgical procedures on recurrence. CONCLUSION: Laparoscopic surgery for gastric GISTs is acceptable for selective patients with better short-term outcomes compared with open surgery. The long-term survival situation of patients mainly depends on the nature of tumor itself, and laparoscopic surgery was not associated with worse oncological outcomes.

Study of ZHENG differentiation in hepatitis B-caused cirrhosis: a transcriptional profiling analysis.

BACKGROUND: In traditional Chinese medicine (TCM) clinical practice, ZHENG (also known as TCM syndrome) helps to understand the human homeostasis and guide individualized treatment. However, the scientific basis of ZHENG remains unclear due to limitations of current reductionist approaches. METHODS: We collected the leukocyte samples of three hepatitis B-caused cirrhosis (HBC) patients with dampness-heat accumulation syndrome (DHAS) and three HBC patients with liver depression and spleen deficiency syndrome (LDSDS) for microarray analysis. We generated Gene-Regulatory-Networks (GeneRelNet) from the differentially expressed genes (DEGs) of microarray date. Core genes were validated using anther independent cohort of 40 HBC patients (20 DHAS, 20 LDSDS) with RT-PCR. RESULTS: There were 2457 mapped genes were differentially expressed between DHAS and LDSDS (Fold change ≥ 2.0, P < 0.05). There were markedly different genes co-expression patterns in DHAS and LDSDS. Furthermore, three differential co-expression genes including purine nucleoside phosphorylase (PNP); aquaporin 7 (AQP7) and proteasome 26S subunit, non-ATPase 2 (PSMD2) were screened by GeneRelNets, and their mRNA expressions were further validated by real time RT-PCR. The results were consistent with microarray. The PNP (P = 0.007), AQP7 (P = 0.038) and PSMD2 (P = 0.009) mRNA expression is significant difference between DHAS and LDSDS using the non-parametric test. Furthermore, we constructed an mRNA panel of PNP, AQP7 and PSMD2 (PAP panel) by logistic regression model, and evaluated the PAP panel to distinguish DHAS from LDSDS by area under the receiver operating characteristic curve (AUC) analysis, which showed a higher accuracy (AUC = 0.835). Gene ontology (GO) analysis indicated that the DHAS is most likely related to system process while the functions overrepresented by LDSDS most related to the response to stimulus. CONCLUSIONS: This study suggested that there are particular transcriptional profiles, genes co-expressions patterns and functional properties of DHAS and LDSDS, and PNP, AQP7, and PSMD2 may be involved in ZHENG differentiation of DHAS and LDSDS in HBC.

Synergistic effect of combinatorial treatment with curcumin and mitomycin C on the induction of apoptosis of breast cancer cells: a cDNA microarray analysis.

In order to explore the synergistic mechanisms of combinatorial treatment using curcumin and mitomycin C (MMC) for breast cancer, MCF-7 breast cancer xenografts were conducted to observe the synergistic effect of combinatorial treatment using curcumin and MMC at various dosages. The synergistic mechanisms of combinatorial treatment using curcumin and MMC on the inhibition of tumor growth were explored by differential gene expression profile, gene ontology (GO), ingenuity pathway analysis (IPA) and Signal-Net network analysis. The expression levels of selected genes identified by cDNA microarray expression profiling were validated by quantitative RT-PCR (qRT-PCR) and Western blot analysis. Effect of combinatorial treatment on the inhibition of cell growth was observed by MTT assay. Apoptosis was detected by flow cytometric analysis and Hoechst 33258 staining. The combinatorial treatment of 100 mg/kg curcumin and 1.5 mg/kg MMC revealed synergistic inhibition on tumor growth. Among 1501 differentially expressed genes, the expression of 25 genes exhibited an obvious change and a significant difference in 27 signal pathways was observed (p<0.05). In addition, Mapk1 (ERK) and Mapk14 (MAPK p38) had more cross-interactions with other genes and revealed an increase in expression by 8.14- and 11.84-fold, respectively during the combinatorial treatment by curcumin and MMC when compared with the control. Moreover, curcumin can synergistically improve tumoricidal effect of MMC in another human breast cancer MDA-MB-231 cells. Apoptosis was significantly induced by the combinatorial treatment (p<0.05) and significantly inhibited by ERK inhibitor (PD98059) in MCF-7 cells (p<0.05). The synergistic effect of combinatorial treatment by curcumin and MMC on the induction of apoptosis in breast cancer cells may be via the ERK pathway.

[The diagnosis and treatment of pancreatic neuroendocrine neoplasms].

OBJECTIVE: To analyze the prognostic factors of pancreatic neuroendocrine neoplasms (PNEN). METHODS: Clinical data of 61 patients with PNEN from March 1992 to December 2012 was retrospectively analyzed. There were 23 male and 38 female patients, with a median age of 52 years (ranged from 22 to 68 years). Forty-one patients were non-functional tumors, and 20 patients were functional tumors. Fifty-nine patients received operation, 13 (22.0%) patients underwent laparoscopic operation, 2 patients underwent puncture biopsy under CT guidance. Survival was analyzed with the Kaplan-Meier method. RESULTS: Among these patients, 53 (86.9%) patients underwent curative resection. The cases of grade G1, G2, G3 were 41 (67.2%), 9 (14.8%), 11 (18.0%), respectively. The cases of stageI, II, III, IV were 47 (77.0%), 7 (11.5%), 2 (3.3%), 5 (8.2%), respectively. Liver metastasis, neural invasion were found in 5 cases (8.2%), 5 cases (8.2%), respectively. The median follow-up period was 40 months (ranged from 3 to 209 months). The overall 1-, 3-, 5-year survival rates were 92.0%, 89.7%, 86.3%, respectively. Univariate analysis showed WHO classification (χ(2) = 18.503), TNM staging system (χ(2) = 23.401), liver metastasis (χ(2) = 18.606), neural invasion (χ(2) = 10.091), resection status (χ(2) = 25.514) were prognostic factors of PNEN (all P = 0.000). CONCLUSIONS: Surgical resection in PNEN results in long-term survival. WHO classification, TNM staging, resection status are effective in predicting the prognosis of PNEN. Liver metastasis, neural invasion predicted poor prognosis.

Photoinduced reductive Reformatsky reaction of α-haloesters and aldehydes or ketones by cooperative dual-metal catalysis.

A photoinduced reductive Reformatsky reaction by cooperative dual-metal catalysis is described. This methodology enables the implementation of this venerable reaction in environmentally friendly conditions, obviating the need for a stoichiometric amount of metals. A broad range of synthetically useful ß-hydroxy esters can be efficiently prepared in moderate to high yields using this protocol.

[Laparoscopic distal pancreatectomy: the experience of 68 cases in a single centre].

OBJECTIVE: To evaluate the feasibility and efficacy of laparoscopic distal pancreatectomy. METHODS: Totally 68 patients (male 23, female 45) aged 17 to 77 years, with distal pancreatic lesions, underwent laparoscopic distal pancreatectomy from November 2003 to December 2010. The clinical data were collected. Safety, feasibility and crucial technique manipulation were analyzed retrospectively. RESULTS: All 68 operations were successful with two cases conversion to open, including 48 cases combined with splenectomy, and 18 cases with preservation of spleen. Fourteen cases received with combination resection of multi-organs, including 4 cases with cholecystectomy, 1 case resection of right adrenal adenoma and cholecystectomy, 1 case with myomectomy and left ovarian teratomectomy; 1 case with right ovarian teratomectomy, 1 case with resection of left adrenal adenoma, 1 case with resection of both adrenal adenoma, 1 case with resection of liver metastasis, 1 case with cholecystectomy and resection of liver metastasis, 1 case with resection of left adrenal adenoma and liver metastasis, 1 case with resection of left adrenal adenoma and colon and spleen, 1 case with biopsy of liver nodule. The mean operative time was (209 ± 58) minutes, the mean intraoperative blood loss was (191 ± 123) ml, and the mean postoperative hospital stay was (8 ± 4) days. The rate of overall postoperative complications was 18.1%, including an 12.1% rate of clinical pancreatic fistula. Only one case needed a reoperation, and there was no postoperative mortality. CONCLUSION: Laparoscopic distal pancreatectomy with or without splenectomy is safe and feasible in the treatment of most distal pancreatic tumors.

Copper-catalyzed direct decarboxylative fluorosulfonylation of aliphatic carboxylic acids.

Sulfonyl fluorides are emerging as key structural motifs in organic synthesis, medicinal chemistry, and materials science. Herein we report two efficient and complementary methods for direct decarboxylative fluorosulfonylation of carboxylic acids by the merging of copper catalysis with different N-centered HAT regents. A wide range of structurally diverse sulfonyl fluorides was readily accessed from primary, secondary, and tertiary carboxylic acids in a single step under mild conditions.