Manganese(I)-Catalyzed Direct C-H Allylation of Arenes with Allenes.

Polysubstituted allyl groups, for example, the prenyl group, are valuable synthetic handles and widely encountered in bioactive compounds. Reported herein is a manganese(I)-catalyzed direct C-H coupling with allenes for the efficient assembly of allylated arenes. The protocol offers an extremely high level of atom-economy and is particularly suited for the introduction of 1,1-disubstitiuted allyl groups, as exemplified by the quantitative syntheses of a variety of prenylated indoles. The practicality of this method was evidenced by a gram-scale synthesis with a lower catalyst loading of manganese(I) (2.5 mol %, 95% yield). Experimental mechanistic studies were conducted, and a possible reaction mechanism was proposed.

Manganese(I)-Catalyzed Regio- and Stereoselective 1,2-Diheteroarylation of Allenes: Combination of C-H Activation and Smiles Rearrangement.

Heteroarenes are important structural motif in functional molecules. A MnI -catalyzed 1,2-diheteroarylation of allenes via a C-H activation/Smiles rearrangement cascade is presented. The reaction occurred under additive-free or even solvent-free conditions, which allowed the creation of two C-C and one C-N bonds in a single operation. A series of structurally diverse bicyclic or tricyclic compounds bearing an exocyclic double bond were constructed in good to excellent efficiency. The decarboxylative ring-opening of the products led to the facile synthesis of vicinal biheteroaryls. Synthetic applications were demonstrated and preliminary mechanistic studies were conducted.

Pancreas-preserving duodenectomy for treatment of a duodenal papillary tumor: A case report.

BACKGROUND: Duodenal papillary tumor is a rare tumor of the digestive tract, accounting for about 0.2% of gastrointestinal tumors and 7% of periampullary tumors. The clinical manifestations of biliary obstruction are most common. Some benign tumors or small malignant tumors are often not easily found because they have no obvious symptoms in the early stage. Surgical resection is the only treatment for duodenal papillary tumors. At present, the methods of operation for duodenal papillary tumors include pancreatoduodenectomy, duodenectomy, ampullectomy, and endoscopic resection. CASE SUMMARY: A 47-year-old man was admitted to because of a duodenal mass that had been discovered 2 mo previously. Electronic gastroscopy at another hospital revealed a duodenal papillary mass that had been considered to be a high-grade intraepithelial neoplasia. Therefore, we conducted a multidisciplinary group discussion and decided to perform a pancreas-preserving duodenectomy and a R0 resection was successfully performed. After surgery, the patient underwent a follow-up period of 5 yr. No recurrence or metastasis occurred. CONCLUSION: According to our experience with a duodenal papillary tumor, compared with pancreaticoduodenectomy, the use of pancreas-preserving duodenectomy can preserve pancreatic function, maintain gastrointestinal structure and function, reduce tissue damage and complications, and render the postoperative recovery faster. Pancreas-preserving duodenectomy for treatment of a duodenal papillary tumor is feasible under strict control of surgical indications.

Giant hemangioma of the caudate lobe of the liver with surgical treatment: A case report.

BACKGROUND: Caudate lobe hemangioma of the liver is relatively rare. Due to the unique anatomical location of the caudate lobe, the caudate lobectomy accounts for only 0.5% to 4% of hepatic resection, which is difficult to operate and takes a long time, and even has many postoperative complications. CASE SUMMARY: A 34-year-old female presented with a 1 year history of intermittent pain in the right side of the waist without obvious inducement. All laboratory blood tests were within normal limits. Indocyanine green 15 min retention was rated 2.9%, and Child-Pugh was rated A. Computed tomography and magnetic resonance imaging diagnosed giant hemangioma of the caudate lobe with hemangioma of left lobe of liver. After discussion, surgical treatment was performed, which lasted 410 min, with intraoperative bleeding of about 600 mL and postoperative pathological findings of cavernous hemangioma. There were no obvious postoperative complications, and the patient was discharged 10 d after surgery. CONCLUSION: Caudate lobectomy is difficult due to its special anatomical location. Under the condition of fully exposing the anatomy of the first porta hepatis, the second porta hepatis, the third porta hepatis, the fourth porta hepatis and middle hepatic vein and combining with the Pringle maneuver, caudate lobectomy can be performed in a precise and safe process.

Application of multiple Roux-en-Y hepaticojejunostomy reconstruction by formation of bile hilar duct lake in the operation of hilar cholangiocarcinoma.

BACKGROUND: Hilar cholangiocarcinoma is the most common malignant tumor of the extrahepatic bile duct. Until now, radical resection has been the most effective method for the long-term survival of patients with the disease. However, many problems have emerged in the field of hepatobiliary surgery for a long time, including complex surgical procedures, low resection rate, and postoperative complications. We have adopted the "multiple Roux-en-Y hepaticojejunostomy reconstruction by formation of a bile duct lake" technique in the treatment of hilar cholangiocarcinoma since 2008, and obtained satisfactory short- and long-term results. AIM: To examine the feasibility of the application of multiple Roux-en-Y hepaticojejunostomy reconstruction by formation of a bile duct lake in the operation of hilar cholangiocarcinoma. METHODS: A retrospective analysis was performed for the clinical data, surgical methods, and results of 76 patients with hilar cholangiocarcinoma who were treated with hilar bile duct lake-forming multiple Roux-en-Y hepaticojejunostomy reconstruction at Gansu Provincial Hospital. RESULTS: In all 76 cases, the operation was successful and no operative death occurred. The mean (range) operation time was 215.4 ± 53.5 min (124-678 min), and the amount of bleeding during the operation was 428.2 ± 63.8 mL (240-2200 mL). The overall 1-year survival rate was 78.9%, and the 3-year survival rate was 32.8%. CONCLUSION: The multiple Roux-en-Y hepaticojejunostomy reconstruction technique with formation of a bile duct lake is safe and effective for the surgical treatment of hilar cholangiocarcinoma.

Increased KIF21B expression is a potential prognostic biomarker in hepatocellular carcinoma.

BACKGROUND: The kinesin superfamily protein member KIF21B plays an important role in regulating mitotic progression; however, the function and mechanisms of KIF21B in cancer, particularly in hepatocellular carcinoma (HCC), are unknown. AIM: To explore the role of KIF21B in hepatocellular carcinoma and its effect on prognosis after hepatectomy. METHODS: First, data on the differential expression of KIF21B in patients with HCC from The Cancer Genome Atlas database was analyzed. Subsequently, the expression levels of KIF21B in HCC cell lines and hepatocytes were detected by reverse transcription-polymerase chain reaction, and its biological effect on BEL-7404 cells was evaluated by KIF21B knockdown. Immunohistochemical analysis was used to validate the differential expression of KIF21B in HCC tissues and adjacent normal tissues from 186 patients with HCC after hepatectomy. The Kaplan-Meier method was used to assess prognosis significance. RESULTS: KIF21B expression levels were significantly higher in HCC tissues than in corresponding adjacent normal tissues. The expression levels of KIF21B in four HCC cell lines were higher than that in normal liver cells. Functional experiments showed that KIF21B knockdown remarkably suppressed cell proliferation and induced apoptosis. Moreover, immunohistochemistry results are consistent with The Cancer Genome Atlas analysis, with KIF21B expression levels being increased in HCC tissues compared to adjacent normal tissues. Univariate and multivariate analyses revealed KIF21B as an independent risk factor for overall survival and disease-free survival in patients with HCC after hepatectomy. CONCLUSION: Taken together, our results provide evidence that KIF21B plays an important role in HCC progression and may be a potential diagnostic and prognostic marker for HCC.

Effect of postoperative early enteral nutrition on clinical outcomes and immune function of cholangiocarcinoma patients with malignant obstructive jaundice.

BACKGROUND: Most cholangiocarcinoma patients with malignant obstructive jaundice (MOJ) have varying degrees of malnutrition and immunodeficiency preoperatively. Therefore, perioperative nutritional support has important clinical significance in the treatment of cholangiocarcinoma. AIM: To investigate the effects of postoperative early enteral nutrition (EEN) on immunity function and clinical outcomes of cholangiocarcinoma patients with MOJ. METHODS: This prospective clinical study included 60 cholangiocarcinoma patients with MOJ who underwent surgery. The patients were randomly divided into an experimental group and a control group according to the nutrition support modes. The control group received postoperative total parenteral nutrition (TPN), whereas the experimental group received postoperative EEN and parenteral nutrition (PN; EEN + PN). The clinical outcomes, postoperative immune function, incidences of surgical site infection and bile leakage, intestinal function recovery time, average hospitalization days, and hospitalization expenses of the two groups were assessed on postoperative days (PODs) 1, 3, and 7. RESULTS: The CD3+T, CD4+T, CD8+T, and CD4+T/CD8+T cell count and the immunoglobulin (Ig) G, IgM, and IgA levels in the EEN + PN group were significantly higher than those in the TPN group on PODs 3 and 7 (P < 0.05), whereas no significant differences in the CD3+T, CD4+T, CD8+T, and CD4+T/CD8+T cell counts and IgG, IgM, and IgA levels before operation and on POD 1 were found between the two groups (P > 0.05). The intestinal function recovery time and postoperative hospital stay were shorter (P < 0.001 for both) in the EEN + PN group than in the TPN group. The hospitalization expenses of the EEN + PN group were lower than those of the TPN group (P < 0.001). However, the incidence of abdominal distension was higher than in the EEN + PN group than in the TPN group (P < 0.05). The incidence rates of biliary leakage and surgical site infection were not significantly different between the two groups (P > 0.05). CONCLUSION: A postoperative EEN program could reduce the incidence of postoperative complications and improve the clinical outcomes and immune functions of cholangiocarcinoma patients with MOJ and is thus beneficial to patient recovery.

Regio- and Stereoselective Alkenylation of Allenoates with gem-Difluoroalkenes: Facile Access to Fluorinated 1,4-Enynes Bearing an All-Carbon Quaternary Center.

A regio- and stereoselective synthesis of fluorinated 1,4-enynes bearing an all-carbon quaternary center at the propargylic position is developed. The synthesis starts from readily available allenoates and gem-difluoroalkenes and proceeds via a key alkynylenolate intermediate following a nucleophilic addition/ß-F elimination. This reaction occurs under mild reaction conditions with good tolerance to a variety of functional groups. Synthetic utility is demonstrated by further transformations of the products. Furthermore, the reaction can also be applied for the synthesis of α-alkenyl allenoates by using 3,3-disubstituted allenoates.

Visual Dominance Effect upon Passing the Central Bottleneck of Information Processing.

BACKGROUND: In the classical psychological refractory period (PRP) paradigm, two stimuli are presented in brief succession, and participants are asked to make separate speeded responses to both stimuli. Due to a central cognitive bottleneck, responses to the second stimulus are delayed, especially at short stimulus-onset asynchrony (SOA) between the two stimuli. Although the mechanisms of dual-task interference in the classical PRP paradigm have been extensively investigated, specific mechanisms underlying the cross-modal PRP paradigm are not well understood. In particular, it remains unknown whether the dominance of vision over audition manifests in the cross-modal PRP tasks. The present study aimed to investigate whether the visual dominance effect manifests in the cross-modal PRP paradigm. METHODS: We adapted the classical PRP paradigm by manipulating the order of a visual and an auditory task: the visual task could either precede the auditory task or vice versa, at either short or long SOAs. Twenty-five healthy participants took part in Experiment 1, and thirty-three new participants took part in Experiment 2. Reaction time and accuracy data were calculated and further analyzed by repeated-measures analysis of variance. RESULTS: The results showed that visual precedence in the Visual-Auditory condition caused larger impairments to the subsequent auditory processing than vice versa in the Auditory-Visual condition: a larger delay of second response was revealed in the Visual-Auditory condition (135 ± 10 ms) than the Auditory-Visual condition (88 ± 9 ms). This effect was found only at the short SOAs under the existence of the central bottleneck, but not at the long SOAs. Moreover, this effect occurred both when the single visual and the single auditory task were of equal difficulty in Experiment 1 and when the single auditory task was more difficult than the single visual task in Experiment 2. CONCLUSION: Results of the two experiments suggested that the visual dominance effect occurred under the central bottleneck of cognitive processing.

Reusable Reinforcement Learning via Shallow Trails.

Reinforcement learning has shown great success in helping learning agents accomplish tasks autonomously from environment interactions. Meanwhile in many real-world applications, an agent needs to accomplish not only a fixed task but also a range of tasks. For this goal, an agent can learn a metapolicy over a set of training tasks that are drawn from an underlying distribution. By maximizing the total reward summed over all the training tasks, the metapolicy can then be reused in accomplishing test tasks from the same distribution. However, in practice, we face two major obstacles to train and reuse metapolicies well. First, how to identify tasks that are unrelated or even opposite with each other, in order to avoid their mutual interference in the training. Second, how to characterize task features, according to which a metapolicy can be reused. In this paper, we propose the MetA-Policy LEarning (MAPLE) approach that overcomes the two difficulties by introducing the shallow trail. It probes a task by running a roughly trained policy. Using the rewards of the shallow trail, MAPLE automatically groups similar tasks. Moreover, when the task parameters are unknown, the rewards of the shallow trail also serve as task features. Empirical studies on several controlling tasks verify that MAPLE can train metapolicies well and receives high reward on test tasks.

Polycyclization Enabled by Relay Catalysis: One-Pot Manganese-Catalyzed C-H Allylation and Silver-Catalyzed Povarov Reaction.

In this study, a MnI /AgI -based relay catalysis process is described for the one-pot synthesis of polycyclic products by a formal [3+2] and [4+2] cycloaddition reaction cascade. A manganese(I) complex catalyzed the first example of directed C-H allylation with allenes, setting the stage for an in situ Povarov cyclization catalyzed by silver(I). The reaction proceeds with high bond-forming efficiency (three C-C bonds), broad substrate scope, high regio- and stereoselectivity, and 100 % atom economy.

Development of a core snubber for the neutral beam injector on EAST.

A 4-MW ion source was developed for the neutral beam injector (NBI) on Experimental Advanced Superconducting Tokamak (EAST). Breakdown nevertheless can happen during ion source conditioning and routine operations and is deleterious to the high-power ion source. To protect this ion source, a core snubber was designed to absorb the breakdown energy of the EAST-NBI ion source. A prototype core snubber was developed and tested using the ion-source test bed. The results show that with a core snubber, short-circuit currents at different high-power voltages were about one-tenth of the current without the snubber. The residual energy of the distributed capacitors had been absorbed successfully and the core snubber does protect the source from damage during breakdown. The results verified the successful development of a core snubber for the EAST-NBI.

[Advances in Detection Technologies of in vivo Expression of Bacterial Virulence Gene.].

The interactions between bacterial pathogens and their hosts is complex. To further our understanding ofathe pathogenesisaof bacterial pathogens, it is necessary to identify bacterial virulence genes that are specifically induced in vivo during infection and probe their regulation in vivo. Toward this end, several technologies, such as in vivo expression technology (IVET), signature-tagged mutagenesis (STM), differential fluorescence induction (DFI), genomic analysis and mapping by in vitro transposition (GAMBIT) and in vivo induced antigen technology (IVIAT), have been developed. The purpose of this reviewais to update the reader on the many advances of these technologies, and to discuss their advantages and disadvantages.

Myricetin induces apoptosis in HepG2 cells through Akt/p70S6K/bad signaling and mitochondrial apoptotic pathway.

The present investigation was undertaken to gain insight into the molecular mechanism by which myricetin induces apoptosis in human hepatocarcinoma HepG2 cells. Myricetin caused the disruption of mitochondrial membrane potential in a dose-dependent manner. Moreover, myricetin triggered translocation of the pro-apoptotic protein Bax to the mitochondria, downregulation of anti-apoptotic Bcl-2 expression and upregulated the expression of pro-apoptotic protein Bad in the mitochondria. The present study also showed that myricetin promoted the release of cytochrome C from mitochondria into the cytosol followed by an increase in the proteolytic activation of caspase-3 and the concomitant degradation of PARP protein. Additionally, western blot analysis showed that the Akt/p70s6k1 pathway was inhibited in myricetin-treated HepG2 cells, accordingly the phosphorylation of Bad at Ser136 was downregulated. Collectively, these findings indicate that myricetin induced apoptosis in HepG2 cell through mitochondria apoptotic pathway and Akt/p70s6k1/Bad signaling. Present results provide new information on the possible mechanisms for the anti-cancer activity of myricetin.

Plasma soluble human leukocyte antigen-G expression is a potential clinical biomarker in patients with hepatitis B virus infection.

The significance of upregulated soluble human leukocyte antigen-G (sHLA-G) expression under various pathologic conditions has been discussed. In this study, we evaluated the potential significance of plasma sHLA-G expression in patients with hepatitis B virus (HBV) infection. The study included 90 acute hepatitis B patients (AHB), 131 chronic hepatitis B patients (CHB), 152 resolved hepatitis B individuals (RHB), and 129 normal controls. sHLA-G were determined using enzyme-linked immunosorbent assay. A receiver operating characteristic (ROC) curve was used to evaluate the feasibility of plasma sHLA-G as a biomarker for distinguishing patients with HBV infection. sHLA-G levels in AHB (median, 193.1 U/mL; p < 0.001), CHB (median, 324.6 U/mL; p < 0.001), and RHB (median, 14.8 U/mL; p = 0.006) patients was much higher than that in normal controls (median, 9.0 U/mL). A significant difference for sHLA-G levels was also observed between patients with HBV infection (AHB vs CHB, AHB vs RHB, and CHB vs RHB; all p < 0.001). The area under the ROC curve for sHLA-G levels was 1.000 (p < 0.001) for AHB, 0.993 (p < 0.001) for CHB, and 0.604 (p = 0.003) for RHB patients versus normal controls, respectively. Data also indicated that the percentage of CD4(+)CD25(+)FoxP3(+) T regulatory cells and HLA-G(+)CD14(+) monocytes was significantly increased in AHB and CHB patients compared with normal controls (all p < 0.001). Our findings indicated that induction of HLA-G expression may play a role in HBV immune evasion and sHLA-G levels could be a useful biomarker in HBV infection.

Induction of both membrane-bound and soluble HLA-G expression in active human cytomegalovirus infection.

BACKGROUND: Alteration of HLA expression or cytokine production plays a crucial role in the pathogenesis of human cytomegalovirus (HCMV) infection. HLA-G has been suggested to be involved in HCMV infection, and modulation of HLA-G expression by interferon (IFN)-gamma and interleukin (IL)-10 has been reported. However, the clinical relevance of HLA-G in HCMV infection remains unknown. METHODS: The study included 75 patients with active HCMV infection (age range, 1-4.5 years) and 150 sex- and age-matched healthy control subjects (age range, 1-5 years). HLA-G expression in peripheral monocytes from patients (n=38) and control subjects (n=20) was analyzed using flow cytometry. Plasma levels of soluble HLA-G (in 75 patients and 150 control subjects), IL-10 (in 75 patients and 40 control subjects), and IFN-gamma (in 75 patients and 40 control subjects) were determined using enzyme-linked immunosorbent assay. RESULTS: The mean percentage of HLA-G-positive monocytes among patients with active HCMV infection was dramatically increased, compared with that among healthy control subjects (6.33% vs 1.64%; P<.001). Similarly, significant increases were observed in soluble HLA-G level (median, 54.91 vs 21.32 U/mL; P<.001) and IL-10 level (median, 9.24 vs 1.82 ng/mL; P<.001). Although the expression of IFN-gamma was higher in patients with active HCMV infection than in healthy control subjects, the difference was not statistically significant (median, 1254.46 vs 887.05 ng/mL; P=.070). Furthermore, no correlation was established between HLA-G expression and levels of IL-10 or IFN-gamma. CONCLUSIONS: HLA-G expression in monocytes and plasma soluble HLA-G and IL-10 levels were increased during active HCMV infection.

[Moxibustion on heat-sensitive acupoints for treatment of myofascial pain syndrome: a multi-central randomized controlled trial].

OBJECTIVE: To observe the clinical therapeutic effect of moxibustion on heat-sensitive acupoints on myofascial pain syndrome (MPS). METHODS: Three-centre, single blind, randomized controlled trial method was adopted. One hundred and seven cases were randomly divided into an observation group (n = 57), and a control group (n = 50). The observation group were treated by moxibustion on the heat-sensitive acupoints and the control group by acupuncture, cupping and TDP. The therapeutic effects were assessed according to changes of the score of the short-form of McGill pain questionnaire composing of pain rating index (PRI), visual analogue scale (VAS) and present pain intensity (PPI) before and after treatment. RESULTS: The cured rate of 86.0% in the observation group was better than 24.0% in the control group. After treatment, the score of PRI, VAS, PPI indexes significantly improved in the observation group (P < 0.001), and were significantly better than those in the control group (P < 0.001). CONCLUSION: Moxibustion on the heat-sensitive acupoints has a high therapeutic effect on MPS.