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Substrate access tunnel engineering is a useful strategy for enzyme modification. In this study, we improved the catalytic performance of Fe-type Nitrile hydratase (Fe-type NHase) from Pseudomonas fluorescens ZJUT001 (PfNHase) by mutating residue Q86 at the entrance of the substrate access tunnel. The catalytic activity of the mutant PfNHase-αQ86W towards benzonitrile, 2-cyanopyridine, 3-cyanopyridine, and 4-hydroxybenzonitrile was enhanced by 9.35-, 3.30-, 6.55-, and 2.71-fold, respectively, compared to that of the wild-type PfNHase (PfNHase-WT). In addition, the mutant PfNHase-αQ86W showed a catalytic efficiency (k cat /K m ) towards benzonitrile 17.32-fold higher than the PfNHase-WT. Interestingly, the substrate preference of PfNHase-αQ86W shifted from aliphatic nitriles to aromatic nitrile substrates. Our analysis delved into the structural changes that led to this altered substrate preference, highlighting an expanded entrance tunnel region, theenlarged substrate-binding pocket, and the increased hydrophobic interactions between the substrate and enzyme. Molecular dynamic simulations and dynamic cross-correlation Matrix (DCCM) further supported these findings, providing a comprehensive explanation for the enhanced catalytic activity towards aromatic nitrile substrates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Acanthopanacis cortex (the dried root bark of Acanthopanax gracilistylus W. W. Smith) has been used for the treatment of rheumatic diseases in China for over 2000 years. Four previously undescribed lignans (1-4) and 12 known lignans (5-16) were isolated from Acanthopanacis cortex. In this study, the inhibitory activities of compounds 1-16 against neutrophil elastase (NE), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are reported. The results show that compounds 1-16 exhibit weak inhibitory activities against NE and COX-1. However, compounds 2, 6-8 and 13-16 demonstrate better COX-2 inhibitory effects with IC 50 values from 0.75 to 8.17 μΜ. These findings provide useful information for the search for natural selective COX-2 inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Acanthopanacis Cortex (A.-C) with a long history of more than1000 years, has been used to treat rheumatism effectively. Nineteen diterpenoids have been isolated from A.-C, including six new compounds (1-6). Among them, compounds 7, 9-11, 13, and 17 were discovered from A.-C for the first time. The structures of 1-6 were determined by analyzing their NMR data and comparing their experimental and calculated electronic circular dichroism spectra. Moreover, the single-crystal X-ray diffraction data of 1, 2, 8, and 14 were provided. The anti-inflammatory activity of 1-5 and 7-18 on neutrophil elastase, cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2) has been studied in vitro, and the results showed that 15 had almost no inhibitory effects on COX-1 at 200 μM but a significant activity against COX-2 with an IC 50 of 0.73 ± 0.006 μΜ. It indicated that compound 15 can provide valuable information for the design of selective COX-2 inhibitors., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Eleven new acyl-quinic acids (AQAs) 1a-9, and 18 known AQAs 10-27 were isolated from the root bark of Acanthopanax gracilistylus W. W. Smith (Acanthopanacis Cortex). The planar structures of 1a-9 were determined based on their HR-ESIMS, IR, and NMR data. The absolute configurations of 1a-6 were identified by comparing the experimental and the calculated electronic circular dichroism (ECD) spectra. This is the first report of the isolation of AQAs from Acanthopanacis Cortex. Notably, 1a-6 were determined as unusual oxyneolignan-(-)-quinic acids heterodimers, representing a new class of natural products. The inhibitory activities of 1a-27 on neutrophil elastase (NE) and cyclooxygenase-2 (COX-2) were studied in vitro, and the results indicated they possessed significant inhibitory activities on COX-2. Among them, the IC 50 values of 1a-9 were 0.63±0.014, 0.75±0.028, 0.15±0.023, 0.63±0.016, 0.30±0.013, 35.63±4.600, 8.70±1.241, 16.51±0.480, 0.69±0.049, 0.39±0.017, and 0.26±0.080 μM, respectively. This study represents the inaugural disclosure of the anti-COX-2 constituents found in Acanthopanacis Cortex, thereby furnishing valuable insights into the exploration of novel COX-2 inhibitors derived from natural reservoirs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Twenty-four monoterpenoids, including three previously undescribed compounds (1-3), were isolated from the root bark of Acanthopanax gracilistylus W. W. Smith (Acanthopanacis Cortex). Their structures were unambiguously established based on spectroscopic analysis (HR-ESIMS, IR, 1D, and 2D NMR), and the absolute configurations of 1-3 were elucidated by comparing their experimental and calculated electronic circular dichroism spectra. In addition, the structure of 8 was confirmed by single-crystal X-ray diffraction. The inhibitory activities of 1-24 against neutrophil elastase, 5-lipoxygenase, and cyclooxygenase-2 (COX-2) were studied in vitro for the first time, and the results showed that compound 24 possessed a significant inhibitory effect on COX-2 with an IC 50 value of 1.53 ± 0.10 μΜ. This research first reported the presence of monoterpenoids in Acanthopanacis Cortex, including one monoterpenoid 2 with an unusual 4/5 bicyclic lactone system, and compounds 4 and 5 have never been reported in nature., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. There is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Tick fauna and zoogeographic distribution of Jiangxi Province remain largely unknown due to the lack of data on distribution, occurrence, and host associations of ticks. Considering this, we collected 1,817 individual samples from natural hosts, humans, and vegetation in 18 counties/districts throughout Jiangxi Province, China, from 2015 to 2021. These 1,817 individuals were found to 13 tick species, 4 genera, and 1 family. In addition, the tick sample data from 8 sampling localities (counties and districts) reported in previous studies were also included in our data. A total of 4,021 individuals, including our sample collection and the previously reported data, were assigned to at least 18 species, 6 genera, and 2 families. One newly recorded species Dermacentor sp. (near D. steini Schulze) was found; three misidentified species (Ixodes acuminatus, Haemaphysalis spinigera, and Haemaphysalis verticalis) reported previously were deleted; and one misidentified species Dermacentor auratus Supino was revised as Dermacentor steini Schulze. In addition, we divided the tick fauna in Jiangxi Province into 5 zoogeographic areas and assigned the 18 tick species collected from 26 localities to these 5 zoogeographic areas. To summarize, our findings provide valuable information on the distribution, tick-host associations, and zoogeographic division of ticks in Jiangxi Province, China. Their molecular characterizations, phylogenetic relationships, and tick-borne pathogens that they may transmit should be further explored., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier GmbH.)

This paper is devoted to the prescribed performance control (PPC) for a class of strict-feedback nonlinear systems with input saturation constraints. With the help of an improved tuning function, the system can achieve the desired steady-state and transient performance in the pre-designed time. A new error transformation function is introduced, which has inherent robustness, so it does not need to use any approximation technique or calculate the analytical derivative. Compared with the relevant results, the proposed scheme has the same lower complexity, but better transient and steady-state performance, although there exists uncertain nonlinearity and uncertain disturbances in the system. Finally, the correctness of the above algorithm is verified by simulation experiments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 ISA. Published by Elsevier Ltd. All rights reserved.)

Introduction: Stomatin-like protein 2 (SLP2) is highly expressed in human first trimester trophoblast cells, but its functions in placental morpho-physiology remain unknown. This study aimed to determine the role of SLP2 in the proliferation and invasion of human first trimester trophoblast cells., Methods: Immunofluorescence was used to determine the expression and localization of SLP2 in normal and miscarriage human first trimester placenta. Western blot was used to determine the expression of SLP2, PCNA, Cyclin D3, N-cadherin, Vimentin, PGC1α and PPARα in HTR-8/SVneo cells. SLP2 was knocked down in the HTR-8/SVneo cells by using si-Slp2. Wound healing and migration assays were used to determine the effect of SLP2 knockdown on the migration and invasion in the HTR-8/SVneo cells. Mitochondrial membrane potential, reactive oxygen species (ROS), ATP production and biogenesis were measured to assess the effects of SLP2 knockdown on mitochondrial functions., Result: SLP2 was strongly expressed in the cytotrophoblasts (CTB), syncytiotrophoblast (STB) and extravillous trophoblasts (EVT) of normal pregnancy placenta as compared to miscarriage placenta. SLP2 was highly expressed in the invasive EVT cell lines, HTR-8/SVneo and HPT-8 compared to the CTB cell line JAR. Knockdown of SLP2 significantly inhibited the migration and invasion of HTR-8/SVneo cells and placental villous explants, and repressed mitochondrial biogenesis and functions in HTR-8/SVneo cells., Discussion: Silencing of SLP2 inhibited the proliferation, migration and invasion of HTR-8/SVneo cells via the impairment of mitochondrial functions. This indicates that the downregulation of SLP2 in miscarriage placenta could be part of the pathogenesis and pathophysiology of the disease., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Autophagy play an important role in tumor chemotherapy resistance. It has been reported that miR-137 expression was reducedand involved in the regulation of sensitivity of PC cells to chemotherapy. However, little is known about the underlying molecular mechanisms. In this study, we hypothesized that miR-137 might sensitize PC cells to chemotherapy thought regulating cell autophagy., Methods: Cell survival was determined with MTT assay. Apoptotic cells were assessed with flow cytometric analysis. Fluorescence intensity of GFP-LC3 and RFP-GFP-LC3 were examined with immunofluorescence analysis to determine the autophagy and autophagic flux level. Western blotting assay was used to determine protein expression levels of LC3II/LC3I, P62, FUNDC1 and ATG5. mRNA expression level of miR-137 was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Dual-luciferase reporter assay was used to evaluate the directly binding of miR-137 with its targets. Xenograft model was setup to evaluate tumor growth., Results: The results showed that doxorubicin (Dox) induced autophagy but downregulated the expression level of miR-137 in pancreatic cancer (PC) cells. In turn, overexpression of miR-137 enhanced the effect of Dox on decreasing cell survival, inducing cell apoptosis and inhibiting autophagy rather than influencing autophagic flux in PC cells. Further mechanistic study identified that ATG5 was a direct target of miR-137. Moreover, overexpression of ATG5 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by higher expression level of miR-137. We also demonstrated that miR-137 sensitized PANC-1 cells to Dox through inhibiting ATG5 and autophagy in vivo., Conclusions: Our findings demonstrated for the first time that miR-137 was able to promote sensitivity of PC cells to chemotherapy via inhibition of autophagy mediated by ATG5. Therefore, miR-137 may act as a potential therapeutic target for pancreatic cancer., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Gracilistones A (1) and B (2), two new eudesmane-type sesquiterpenoids with an unusual tetrahydrofuran-fused 6/6/5 tricyclic ring system, were obtained from Acanthopanax gracilistylus under the guidance of LC-MS investigation. Their structures and absolute configurations were assigned by extensive spectroscopic analyses and quantum calculation methods. Compounds 1 and 2 showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, compared with the positive control L-NMMA. In addition, compounds 1 and 2 were also evaluated for their antioxidant (DPPH • and ABTS •+ ) and xanthine oxidase (XO) inhibitory activities, and they exhibited weak inhibitory effects at 100 μM., (Copyright © 2018. Published by Elsevier B.V.)

Background: The efficacy of patent foramen ovale (PFO) closure for secondary stroke prevention in cryptogenic stroke (CS) patients with PFO is uncertain. This meta-analysis aims to assess whether PFO closure is superior to medical therapy., Methods: Pooled estimates were calculated using Revman 5.3. The two primary endpoints were stroke and transient ischemic attack (TIA). Secondary outcomes included all-cause mortality, new-onset atrial fibrillation or flutter, major bleeding and any adverse event., Results: Five randomized controlled trials were included. A total of 3440 patients were randomized to either PFO closure (n = 1829) or medical therapy group (n = 1611) and followed for average 2.0-5.9 years. PFO closure reduced the incidence of recurrent stroke in CS patients with PFO compared to medical therapy (Risk ratio (RR) 0.42, 95% confidence intervals (CI) 0.20-0.91, P = 0.03; hazard ratio (HR) 0.34, 95% CI 0.15-0.78, p = 0.01). There were no significant differences between the two groups in TIA (RR 0.78, 95% CI 0.53-1.15, P = 0.21; HR 0.73, 95% CI 0.49-1.09, p = 0.12), all-cause mortality (RR 0.76, 95% CI 0.35-1.63, P = 0.48), major bleeding (RR 0.96, 95% CI 0.42-2.20, P = 0.93) and any adverse event (RR 1.06, 95% CI 0.95-1.18, P = 0.29). Higher risk of new-onset atrial fibrillation or flutter was found in closure group (RR 4.69, 95% CI 2.17-10.12, P < 0.0001)., Conclusions: PFO closure combined with medical therapy showed superiority over medical therapy alone for stroke prevention in carefully selected CS patients with PFO, but increased the risk of atrial fibrillation or flutter., (Copyright © 2018. Published by Elsevier B.V.)

Oxygen and glucose deprivation (OGD)-re-oxygenation (OGDR) exposure to endometrial cells mimics ischemia-reperfusion injury. The present study tests the potential effect of keratinocyte growth factor (KGF) on the process. We show that KGF receptor KGFR is expressed in human endometrial T-HESC cells and primary murine endometrial cells. KGF pre-treatment protected endometrial cells from OGDR, inhibiting cell viability reduction and cell death. KGF attenuated OGDR-induced programmed necrosis in endometrial cells. Significantly, KGF activated Nrf2 signaling, causing Nrf2 Ser-40 phosphorylation, protein stabilization, nuclear translocation to promote anti-oxidant gene (HO1, NOQ1 and GCLC) expression. Nrf2 silencing (by targeted shRNAs) or CRISPR/Cas9 knockout almost abolished KGF-induced endometrial cell protection against OGDR. Furthermore, KGF activated Akt-mTOR signaling in endometrial cells. Whereas Akt-mTOR inhibitors (LY294002, AZD2014 and RAD001) abolished KGF-induced Nrf2 activation and anti-OGDR cytoprotection. Together, KGF protects endometrial cells from OGDR via activating Akt-mTOR-Nrf2 signaling., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Bifidobacterium preparations are increasingly used for pediatric antibiotic-associated diarrhea (AAD) in China. The aim of this study was to review existing evidence on the efficacy of Bifidobacterium preparations for the prevention and treatment of pediatric AAD in China. Searches were performed with Medline, Embase, Cochrane Central Register of Controlled Trials, CNKI, and CBM databases. Thirty trials met the inclusion criteria. Of the 30 trials, five Bifidobacterium preparations were included. The preparations were all Bifidobacterium based, in combined with Lactobacillus, Enterococcus, Bacillus, Streptococcus or Clostridium strains. The pooled results of the 30 trials, which included 7225 participants, indicated a statistically significant association of Bifidobacterium preparations administration with reduction in pediatric AAD (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.29-0.39; P<0.01). When the meta-analysis was re-performed according to the trials explicitly aiming to prevent or treat pediatric AAD, respectively, the pooled results were similar (Bifidobacterium preparations use for preventing pediatric AAD (n=21): pooled OR, 0.34, 95% CI, 0.28-0.41, P<0.01; Bifidobacterium preparations use for treating pediatric AAD (n=9): pooled OR, 0.32, 95% CI, 0.23-0.43, P<0.01). Subgroup analyses which based on Bifidobacterium preparations variety, clinical condition, or participant's age also showed statistically significant benefit of adjunct Bifidobacterium preparations for the prevention and treatment of pediatric AAD in China. The pooled evidence suggested that Bifidobacterium preparations might be efficacious for the prevention and treatment of pediatric AAD in China., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The present study was to investigate whether Z-guggulsterone had the regulatory effect on the activity and expression of P-glycoprotein in rat brain microvessel endothelial cells (rBMECs) and in rat brain. Inorganic phosphate liberation assay, high performance liquid chromatography, and western blot analysis were performed to assess the P-glycoprotein ATPase activity, the accumulation of NaF and rhodamine 123, and P-glycoprotein and MRP1 expression. The results showed that Z-guggulsterone (0-100 μM) significantly enhanced basal P-glycoprotein ATPase activity in a concentration-dependent manner. Tetrandrine (0.1, 0.3, 1 μM) or cyclosporine A (0.1, 0.3, 1 μM) had non-competitively inhibitory manner on Z-guggulsterone-stimulated P-glycoprotein ATPase activity, suggesting that Z-guggulsterone might have unique binding site or regulating site on P-glycoprotein. However, Z-guggulsterone (30, 100 μM) had almost no influence on MRP1 expression in rBMECs. Further results revealed that Z-guggulsterone (50mg/kg) significantly increased the accumulation of rhodamine 123 by down-regulating P-glycoprotein expression in rat brain, as compared with control (P<0.05). Our studies suggested that Z-guggulsterone potentially inhibited the activity and expression of P-glycoprotein in rBMECs and in rat brain., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Paeoveitols A-E (1-5), involving three monoterpenes and two benzofuran constituents, were isolated from Paeonia veitchii. Their structures were determined based on extensive spectral analyses (IR, UV, MS, 1D and 2D NMR), and the absolute configuration of compound 1 was confirmed by single-crystal X-ray diffraction. By the agitating human melatonin receptor 1 (MT1) assay on HEK293 cell line in vitro, compound 4 showed weak activity with the agitation rate of 22.52% at the concentration of 1.79 mM., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Several studies have suggested that Chinese herb medicine (CHM) in combination with chemotherapy has efficacy in the treatment of multidrug-resistant tuberculosis (MDR-TB). The purpose of this meta-analysis was to assess the efficacy of CHM as a concomitant therapy for MDR-TB. Six databases were searched up to October 2014. Controlled trials comparing CHM combined with chemotherapy (treatment group) with chemotherapy alone (control group) for the treatment of MDR-TB were analyzed. Twenty studies, comprising 1823 patients across China, were included in this review. The meta-analysis showed CHM combined with chemotherapy was associated with a superiority in treatment success (odds ratio [OR], 1.33; 95% confidence interval [CI]: 1.15-1.54; P<0.001), and radiological improvement (OR, 1.32; 95% CI: 1.14-1.52; P<0.001). Patients who received CHM combined with chemotherapy were associated with a similar likely to relapse (OR, 0.88; 95% CI: 0.62-1.25, P=0.478). CHM combination with chemotherapy appeared to be associated with a low incidence of adverse effects for MDT-TB treatment. According to the pooled results and the poor quality of the included trials, it might be uncertainty that there was a superiority of CHM combined with chemotherapy for treating MDR-TB. More rigorous controlled trials are required to substantiate or refute these early findings., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Six new 14-noreudesmane sesquiterpenoids, nicotabacosides A-F (1-6), along with five known sesquiterpenoids (7-11), were isolated from the leaves of Nicotiana tabacum. The structures of compounds 1-6 were elucidated as isorishitin 3-O-β-D-glucopyranoside (1), rishitin 3-O-β-D-glucopyranoside (2), rishitin 2-O-β-D-glucopyranoside (3), 1, 6-dehydro-rishitin 3-O-β-D-glucopyranoside (4), 2-hydroxyl-ligudentatol 3-O-β-D-glucopyranoside (5) and oxyglutinosone 3-O-β-D-glucopyranoside (6) based on extensive spectroscopic analyses (HRESIMS, UV, IR, 1D and 2D NMR). Their absolute configurations were determined by X-ray single-crystal diffraction and comparison of their electronic circular dichroism (ECD) spectra., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Cu/Zn superoxide dismutase (SOD1) is a key antioxidant enzyme. Deficiency of SOD1 is associated with various human diseases, including cancer. Here, we report that SOD1 is succinylated and that succinylation decreases its activity. SIRT5 binds to, desuccinylates and activates SOD1. SOD1-mediated ROS reduction is increased when SIRT5 is co-expressed. Furthermore, mutation of the SOD1 succinylation site inhibits the growth of lung tumor cells. These results reveal a novel post-translational regulation of SOD1 by means of succinylation and SIRT5-dependent desuccinylation, which is important for the growth of lung tumor cells., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Clofazimine has shown activity against Mycobacterium tuberculosis, including multidrug-resistant strains in vitro and in animal studies. However, clinical experience with clofazimine in multidrug-resistant tuberculosis (MDR-TB) is scarce. We reported our clinical experience with 39 MDR-TB patients treated with combination regimens that included clofazimine. From January 2008 to March 2011, 39 patients received clofazimine for the treatment of MDR-TB in Shanghai Pulmonary Hospital. Patients had isolates resistant to a median of six drugs (range, 2-11 drugs). Of the 39 cases, 36 had cavitary changes noted on initial chest radiograph or chest computed tomography, and positive sputum-smear microscopy results at the time of MDR-TB diagnosis. At data censure, 15 of the 39 patients had successful therapy, with at least five consistently negative cultures documented for the final 12 months of treatment. Eleven continued to receive treatment. There were no deaths. Thirteen patients had a poor outcome, including four defaults and nine treatment failures. Culture conversion occurred in 22 cases at a median of 12 weeks. Side-effects occurred in 34 patients, mainly including skin discolouration, ichthyosis and gastrointestinal adverse events. No patients reported significant toxicity likely to be attributable to clofazimine therapy. Adverse events were managed by combinations of dose adjustment and symptom management. In our experience, clofazimine was well tolerated and may have efficacy in the treatment of MDR-TB., (© 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.)

Background: Acute hepatic failure (AHF) is a devastating clinical syndrome with a high mortality rate. The outcome of AHF varies with etiology, but liver transplantation (LT) can significantly improve the prognosis and survival rate of such patients. This study aimed to detect the role of LT and artificial liver support systems (ALSS) for AHF patients and to analyze the etiology and outcome of patients with this disease., Methods: A retrospective analysis was made of 48 consecutive patients with AHF who fulfilled the Kings College Criteria for LT at our center. We analyzed and compared the etiology, outcome, prognosis, and survival rates of patients between the transplantation (LT) group and the non-transplantation (N-LT) group., Results: AHF was due to viral hepatitis in 25 patients (52.1%; hepatitis B virus in 22), drug or toxic reactions in 14 (29.2%; acetaminophen in 6), Wilson disease in 4 (8.3%), unknown reasons in 3 (6.3%), and miscellaneous conditions in 2 (4.2%). In the LT group, 36 patients (7 underwent living donor LT, and 29 cadaveric LT) had an average model for end-stage liver disease score (MELD) of 35.7. Twenty-eight patients survived with good graft function after a follow-up of 27.3+/-4.5 months. During the waiting time, 6 patients were treated with ALSS and 2 of them died during hospitalization. The 30-day, 12-month, and 18-month survival rates were 77.8%, 72.2%, and 66.7%, respectively. In the N-LT group, 12 patients had an average MELD score of 34.5. Four patients were treated with ALSS and all died during hospitalization. The 90-day and 1-year survival rates were only 16.7% and 8.3%, respectively., Conclusions: Hepatitis is the most prominent cause of AHF at our center. Most patients with AHF, who fulfill the Kings College Criteria for LT, did not survive longer without LT. ALSS did not improve the prognosis of AHF patients, but may extend the waiting time for a donor. Currently, LT is still the most effective way to improve the prognosis of AHF patients.

Clinical trials have reported conflicting results as to whether Aromatase inhibitors (AIs) as first-line hormonal therapy improve outcome over tamoxifen in postmenopausal women with advanced breast cancer. We performed a meta-analysis comparing primary and secondary endpoints of AIs to tamoxifen as first-line hormonal therapy in postmenopausal women with advanced breast cancer. The event-based odds ratio (OR) with 95% confidence interval (95% CI) were derived, and a test of heterogeneity was applied. Six eligible trials (2560 patients) were selected from 488 studies that initially were identified. A significant difference in favoring AIs over tamoxifen was observed in overall response rate (ORR; OR, 1.56; 95% CI, 1.17-2.07; P = .002) and clinical benefit (CB; OR, 1.70; 95% CI, 1.24-2.33; P = .0009).Whereas the trend toward an improved overall survival (OS) rate was not significant (OR, 1.95; 95% CI, 0.88-4.30; P = .10).Toxicities did not differ significantly except vaginal bleeding (OR, 0.30; 95% CI, 0.16-0.56; P = .0002) and thromboembolic event (OR, 0.47; 95% CI, 0.28-0.77; P = .003). AIs appeared to be effective and feasible compared with tamoxifen as first-line hormonal therapy in postmenopausal women with advanced breast cancer. Further prospective, randomized, controlled trials will be necessary., (Copyright © 2011. Published by Elsevier Inc.)

Chelerythrine (CHE), a quaternary benzo[c]phenanthridine alkaloid, which is an agent in traditional Chinese medicine exhibits a wide spectrum of pharmacological effects. In this study, we examined the anti-inflammatory activities and mechanism of CHE in vivo and in vitro, respectively. Further, in the analgesic test, CHE also showed pronounced inhibition of the acetic acid-induced writhing response. These results clearly suggested that CHE is a bioactive agent which has a significant anti-inflammatory action, which may be relevant to the inhibition of the release/production of exudates and prostaglandin E(2) mediated through cyclooxygenase-2 regulation., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: Accumulating evidence suggests that adiponectin plays an important role in the genesis of obesity and insulin resistance. Although it has been shown that glucocortocoids (GC) inhibit adiponectin expression in vitro, there exist discrepant results in vivo. In this study, we observe the effect of GC on the serum adiponectin level and adiponectin expression in white adipose tissue (WAT) in male SD rats., Methods: An obese rat model was made by a high-fat diet. Both non-obese and obese rats were randomly divided into normal saline (intraperitoneal injection with normal saline 0.2ml/100gday for 20 days, NS), a low dose GC group (intraperitoneal injection with hydrocortisone sodium succinate 5mg/kgday for 20 days, LDG) and a high dose GC group, respectively (intraperitoneal injection with hydrocortisone sodium succinate 15mg/kgday for 20 days, HDG). Serum adiponectin levels were detected by ELISA and the adiponectin mRNA level was assayed by Northern blot., Results: The serum adiponectin level significantly decreased after 80 days of the high-fat diet (P<0.05), while it was not decreased after 80 days of the chow diet (P>0.05). The serum adioponectin levels in both the non-obese and obese rats were significantly decreased after a 20-day GC injection period (P<0.01). The adiponectin mRNA levels in epididymal fat after high dose GC injection, in both non-obese and obese rats were also decreased (P<0.001)., Conclusions: A high-fat diet decreased serum adiponectin levels in the rat. GC decreased serum adiponectin levels, and this might be due to inhibited adiponectin mRNA expression in WAT. High-fat diet and GC have a synergistic effect on inhibiting adiponectin expression in rats., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Stone recurrence is a major problem in the medication of gallstones with gallbladder preservation. The aim of this study was to determine the long-term recurrence rate of gallstones and the clinical outcome after successful percutaneous cholecystolithotomy (PCCL) treatment, and to investigate the possible risk factors for gallstone recurrence., Methods: After successful PCCL for gallstones, 439 patients were followed up during a 10-year period. The long-term gallstone recurrence rate and clinical outcome were evaluated. Risk factors associated with stone recurrence were identified., Results: Gallstone recurrence was detected in 182 of 439 PCCL patients, giving an overall recurrence rate of 41.46%. The cumulative gallstone recurrence rate for each of the 10 post-operative years was 9.57%, 18.91%, 27.33%, 34.14%, 37.59%, 39.86%, 41.90%, 42.73%, 42.85%, and 43.21%, respectively. Among these recurrent patients, 94 were asymptomatic, 80 suffered from nonspecific upper gastrointestinal symptoms and 8 suffered from abdominal pain or biliary colic. Thirty-eight of the 182 patients were retreated with cholecystectomy. The risk factors for stone recurrence included a family history of gallstones, preference for fatty food, accompanying liver disease, multiple stones and poor gallbladder function pre-PCCL., Conclusions: In this study, the overall recurrence rate of gallstone was 41.46% during a 10-year period. The highest frequency of gallstone recurrence was during the 5th to 6th postoperative years and then continued to slowly increase. Risk factors for stone recurrence varied. We suggest that the use of PCCL in patients with gallstones should be considered carefully because of stone recurrence.

Objective: Mutations in mtDNA are thought to be responsible for the pathogenesis of maternally inherited diabetes. Here, we report a family with maternally inherited diabetes and deafness whose members did not harbour the mtDNA A3243G mutation, the most frequent point mutation in mitochondrial diabetic patients. This study aimed to investigate a possible other mtDNA mutation and its prevalence in type 2 diabetic patients., Methods: Height, body weight, waistline, and hip circumference were measured and serum biochemical marks determined in all members of the family. In addition, a 75 g oral glucose tolerance test and electric listening test were conducted in these members. Genomic DNA was prepared from peripheral leukocytes. Direct sequencing of PCR products was used to detect the mtDNA mutation in this family. The prevalence of mtDNA G3421A nucleotide substitutions was investigated by restriction fragment length polymorphism analysis in 1350 unrelated type 2 diabetic patients recruited by random cluster sampling from the central city area of Shanghai, China., Results: (1) A new missense homoplasmic mutation of mtDNA G3421A was found in a maternally inherited diabetic family and existed neither in 1350 unrelated type 2 diabetic patients nor in 50 non-diabetic individuals. (2) The mode of mutation and diabetes transmission was typical maternal inheritance in this family. (3) All diabetic family members were found to have an onset at 35-42 years of age, accompanied by deafness of varying degrees., Conclusion: mtDNA G3421A (Val39Ile) found in a family with maternally inherited diabetes and deafness is a novel missense mutation. Whether this is a diabetogenic mutation and its effect on mitochondrial function needs to be further studied.

Background: Clinical application of laparoscopy, duodenoscopy and choledochoscopy has been accepted as a mini-invasive surgical therapy for bile duct diseases; but either endoscopic or laparoscopic therapy alone is disadvantageous in its narrow indications and in failure to give full play to the individual superiority. The present study was to evaluate the procedures and therapeutic results of combined laparoscopic and endoscopic treatment for bile duct diseases., Methods: Clinical data of 1990 patients with bile duct diseases treated by combination of laparoscopy, duodenoscopy and choledochoscopy in two hospitals were reviewed and analyzed., Results: Patients with cholecystolithiasis and choledocholithiasis were treated with combined laparoscopy and duodenoscopy (n=1350) in a single operation with a cure rate of 93.6%. Those with choledocholithiasis (n=332) were treated with combined laparoscopy and choledochoscopy with a cure rate of 100%. Combined laparoscopy, duodenoscopy and choledochoscopy was used in 258 patients with choledocholithiasis (29 of them complicated with pancreatitis) and 24 patients with Mirizzi's syndrome, with a cure rate of 100%. Laparoscopic choledochoenterostomy and preoperative endoscopic nasobiliary drainage were done in 26 patients with a cure rate of 100%. There were no serious operative complications. A follow-up study of 1051 patients for 3 months to 12 years (mean 7.8 years) showed that 10 patients had recurrence of stones but no stenosis of the bile duct., Conclusion: Combined laparoscopic and endoscopic procedures are mini-invasive and cause less pain and minimal operative complications.

The antibacterial and antifungal properties of the ethanol extract of Erigeron breviscapus whole plant was evaluated. The extract showed a moderate antibacterial activity and a high antifungal activity.

Transmucosal delivery is a suitable route for insulin non-injection administration. In this study, the hypoglycaemic effect of INSULIN BUCCAL SPRAY (IBS), a formulation with soybean lecithin and propanediol combined as absorption enhancer for insulin on diabetic rabbits and rats, were investigated. The hypoglycaemic rate was calculated and the pharmacodynamics and pharmacokinetics of the formulation in rabbits were studied. The results show that when the diabetic rabbits were administrated with IBS in dosages of 0.5, 1.5 and 4.5Ukg(-1), the blood glucose level decreased significantly compared with that of the control group and the hypoglycaemic effect lasted over 5h. The blood glucose decreasing rates are 22.4, 48.1 and 53.5%, respectively. The average bioavailability of IBS by buccal delivery versus subcutaneous injection is 29.2%. Meanwhile, the diabetic rats were administrated with IBS in dosages of 1.0, 3.0 and 9.0Ukg(-1), the blood glucose level decreased significantly compared with that of the control group and the hypoglycaemic effect lasted over 4h. The blood glucose decreasing rates are 24.6, 47.5 and 59.6%, respectively. Furthermore, the penetration of fluorescein isothiocyanate (FITC)-labelled insulin through rabbit buccal mucosa was investigated by scanning the distribution of the fluorescent probe in the epithelium using confocal laser scanning microscopy. The results revealed that FITC-insulin can pass through the buccal mucosa promoted by the enhancer and the passage of insulin across the epithelium includes both intracellular and paracellular routes. From the rabbit and rat experimental results showed that IBS is an effective buccal delivery system, which is promising for clinical trial and the future clinical application.