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Abstract: Reconstruction of total facial deformities and defects has been a major challenge of reconstructive surgery. Allotransplantation is limited by the number of donors and the need for life-long immunosuppression. Autotransplantation, where multiple autogenous tissue grafts from various donor sites are used to repair facial defects, inevitably leaves conspicuous patchwork scars. A prefabricated monoblock flap, although the preferred treatment modality, is limited by insufficient blood supply and the large size of the flap. In the Journal of Craniofacial Surgery (2014;25:21-25), Li et al applied the technique of flap prefabrication and stem cell-assisted tissue expansion to reconstruct total facial injuries, but the operations were complicated and the final expanded flap area was also uncertain. This article introduces an approach to reconstruct total facial injuries with a prefabricated expanded thoracic flap combined with an expanded scalp flap (called combined flaps), which not only solves the limitations of blood supply and expanded volume but also reduces patchwork scars. The approach is a simple, feasible, and effective surgical method for total face resurfacing., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: There has been an increase in use of autologous costal cartilage for nasal tip shaping material. However, there are deficiencies in using this plastic material, such as a hard nasal tip, poor nasal tip elasticity and mobility postoperatively, and some nasal tip skin thinning that allows the shape of the cartilage grafts to be felt on the surface of the nasal tip skin. To address these problems, we have combined autologous nasal septum cartilage and conchal cartilage as nasal tip graft materials, which achieve a natural shape and realistic touch postoperatively., Methods: From January 2017 to September 2019, a total of 47 patients with nasal septal cartilage combined with conchal cartilage transplantation for nasal tip plasty were screened for a retrospective study. They were followed up and evaluated for 6 to 25 months postoperatively. The operation was performed through an incision in the nose. During the operation, a piece of septal cartilage was cut to make a columella strut. Using one side of the cavitas conchae and cymba conchae cartilage as the graft material, 2 long strips of cartilage were excised for the septum extension graft, and a piece of cap cartilage was transplanted to the top of the nasal tip cartilage scaffold., Results: The time between the operation and follow-up was greater than 6 months, with the range of follow-up and evaluation being from 6 to 25 months. Forty-six patients were satisfied with the shape of the nose. One patient complained that the nasal tip was round and large after 1 month postoperatively, but after 6 months, he was satisfied with the shape of the nasal tip after daily use of a nasal clip. In one male case, the implant was removed more than 7 months postoperatively because of hematoma and infection secondary to nasal trauma. There were 2 cases of nasal tip numbness, both of which recovered spontaneously after 12 months. After the operation, the shape of the nasal tip was round, no cartilage contour was seen on the surface, no collapse of upper nasal tip, no obvious deviation of the nasal dorsum and columella, and no deformation and displacement of the nasal tip cartilage scaffold. At the 6-month follow-up visit, each patient palpated the nasal tip for evaluation. Most patients felt their nose felt realistic and that they had good nasal tip motion. Only 1 patient felt that the nasal tip and the nasal dorsum were moving together when the tip of the nose was being pushed., Conclusions: Nasal septum cartilage and conchal cartilage can be combined as a graft material for reconstruction of the nasal tip. This technique uses different characteristics of each of the 2 cartilages to achieve a more realistic and esthetic outcome., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

To date, a large number of mutations have been screened from breast and ovarian cancer patients. However, most of them are classified into benign or unidentified alterations due to their undetectable phenotypes. Whether and how they could cause tumors remains unknown, and this significantly limits diagnosis and therapy. Here, in a study of a family with hereditary breast and ovarian cancer, we find that two BARD1 mutations, P24S and R378S, simultaneously exist in cis in surviving cancer patients. Neither of the single mutations causes a functional change, but together they synergetically impair the DNA damage response and lead to tumors in vitro and in vivo. Thus, our report not only demonstrates that BARD1 defects account for tumorigenesis but also uncovers the potential risk of synergetic effects between the large number of cis mutations in individual genes in the human genome.

Purpose: Intracerebral hemorrhage (ICH) is a common disease that is known for its high morbidity, high mortality, and high disability. The fast and accurate detection of ICH is essential for the acute care of patients. Electrical impedance tomography (EIT) offers an alternative with which pathological tissues can be detected by reconstructing conductivity variation. Nevertheless, the sensitive field of EIT is greatly affected by medium distribution, which is referred to as soft-field effect. In addition, the image reconstruction is a severely ill-posed inverse problem. Furthermore, due to the low conductivity of skull, the sensitivity in the sensing area is extremely low. Therefore, the reconstruction of ICH with EIT is great challenge. Approach: A sparse image reconstruction method is proposed for EIT to visualize the conductivity variation caused by ICH. To reduce the impact of soft-field effect, the normalization of sensitivity distribution is conducted for monolayer and three-layer head model. In addition, a constrained sparse L 1 -norm minimization model is developed for the image reconstruction. Augmented Lagrangian multiplier method and alternating minimization scheme are adopted to solve the proposed model. Results: The results show that the sensitivity in the sensing area is largely enhanced. Numerical simulation based on monolayer head model and three-layer head model is respectively carried out. Both the reconstructed images and the quantitative evaluations show that image reconstructed by the proposed method is much better than that reconstructed by traditional Tikhonov method. The reconstructions evaluated under the impact of noise also show that the proposed method has superior anti-noise performance. Conclusions: With the proposed method, the quality of the reconstructed image would be greatly improved. It is an effective approach for imaging ICH with EIT technique., (© 2021 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Recent developments in breast cancer therapy have significantly improved patient survival rate; however, recurrence remains a major problem. Systemic treatment of breast cancer with available therapies is not curative. Natural products can be potentially used for treating cancer. Recently, a wide range of pharmacological activities has been reported for Alismatis Rhizoma, a popular traditional Chinese medicine. However, the mechanisms via which its compounds act on breast cancer remain unclear. The present study aimed to investigate the potential of natural therapeutic agents from Alismatis Rhizoma for treating breast cancer. Human breast cancer MDA‑MB‑231 cells were treated with four main protostane triterpenes from Alismatis Rhizoma, including alisol A, alisol A 24‑acetate, alisol B and alisol B 23‑acetate. Among these, alisol A significantly inhibited cell viability. Alisol A induced cell apoptosis, G1 phase cell cycle arrest, autophagy, and intracellular reactive oxygen species (ROS) generation in MDA‑MB‑231 cells. The number of APE1‑/γH2AX‑/LC3‑II positive cells was also significantly higher compared with that of negative control cells. All these results were dose‑dependent. Cleaved caspase‑3, cleaved caspase 9, Bcl‑2, and p‑p38 expression indicated cell apoptosis after alisol A treatment. The changes in cyclin A and cyclin D1 expression was associated with cell cycle arrest upon alisol A treatment. Furthermore, LC3‑II expression upon alisol A treatment was indicative of autophagy. Alisol A treatment can induce autophagy‑dependent apoptosis in human breast cancer cells via induction of ROS and DNA damage. Thus, Alisol A might serve as a new therapeutic agent against breast cancer.

Goal: The goal of this study was to compare the efficacy and safety of endoscopic submucosal tunnel dissection (ESTD) with endoscopic submucosal dissection (ESD) for the removal of early-stage esophageal squamous cancer wider than or equal to one half the circumference of the esophagus., Background: Although ESD has been successfully applied for resection of early-stage esophageal cancer, there are still technical challenges and postoperative stenosis when it is applied to treat large lesions., Patients and Methods: A total of 40 patients with early-stage esophageal cancer wider than or equal to one half its circumference were enrolled in this study and randomly assigned to an ESTD or ESD group for treatment of esophageal superficial squamous cell carcinoma. All of the patients received oral steroids after endoscopic dissection. We then compared the 2 groups in terms of average operating time, dissection speed, en bloc resection rate, R0 resection rate, and complications during a 1-year follow-up period., Results: The dissection speed in the ESTD group was significantly faster than that in the ESD group (P=0.047). There were no significant differences in operating time, en bloc resection rates, or R0 resection rates between the ESTD and ESD group (P=0.319, 1.000, 1.000, respectively). There were also no significant differences in perforation, bleeding, or stenosis rates between the ESTD and ESD group (P=1.000, 0.748, 1.000, respectively)., Conclusion: Both ESTD and ESD are safe and effective therapies for early-stage esophageal cancer wider than or equal to one half the esophageal circumference. The dissection speed of ESTD is faster than that of ESD.

Graphene-based materials have been demonstrated to facilitate electron extracellular transfer (EET) of Shewanella. In this study, compared to group lacking graphene oxide (GO)-based materials, GO films-added group and graphene oxide/polyvinyl alcohol (GO/PVA) film-added group delivered 2.67- and 3.13-fold increases in the Cr(VI) reduction by Shewanella xiamenensis, respectively. The whole reduction process could be divided into three stages, including microbial Cr(VI) reduction and GO reduction stage, microbial GO reduction stage and microbial Cr(VI) reduction mediated by reduced graphene oxide (rGO) stage. Moreover, gene analysis revealed that addition of GO and GO/PVA films stimulated overexpression of several c-type cytochrome (c-Cyts) genes, including mtrA, mtrB, mtrC, mtrD, mtrE, mtrF, omcA, petC and SO-4047. Specifically, appreciable Cr(VI) reduction by the strains that overexpressed mtrA, mtrB, mtrC, mtrD, mtrE, mtrF and omcA further confirmed that overexpression of c-Cyts genes indeed enhanced the efficiency of Cr(VI) reduction. Based on these results, the specific function of every c-Cyt was clearly found in Cr(VI) reduction by the induction of GO-based materials. Our finding has disclosed a synergetic mechanism stimulated by GO-based materials to enhance Cr(VI) bioreduction that was not only mediated through the modification of material but also upregulated the expression of functional genes., 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 © 2020 Elsevier B.V. All rights reserved.)

Background: Recent studies have shown that gastrokine 1 (GKN1), an important tumor suppressor gene, is downregulated in Helicobacter pylori (H. pylori) infected gastric mucosa and gastric cancer. However, the underlying mechanism is poorly understood. Herein, we investigated the potential mechanism of H. pylori-induced GKN1 downregulation., Materials and Methods: GKN1 and AU-rich element RNA-binding factor 1 (AUF1) expressions were assessed by quantitative real-time PCR, Western blot, or immunohistochemistry in H. pylori-infected tissues and H. pylori co-cultured cell lines. The regulation of AUF1 on GKN1 was determined by RNA pulldown assay, RNA immunoprecipitation, mRNA turnover, and luciferase activity assays. The involvement of phosphorylated extra-cellular signal-regulated kinase (p-ERK) or CagA in H. pylori-induced AUF1 expression was verified using p-ERK inhibitor or CagA knockout H. pylori. In addition, the cell proliferation and migration capacities of AUF1-knockdown cells were investigated., Results: GKN1 expression progressively decreased from H. pylori-infected gastritis to gastric cancer tissues. H. pylori co-culture also induced significant GKN1 reduction in GES-1 and BGC-823 cells. Besides, the mRNA level of GKN1 and AUF1 in human gastric mucosa showed negative correlation significantly. AUF1 knockdown resulted in upregulation of GKN1 expression and promoted GKN1 mRNA decay by binding the 3' untranslated region of GKN1 mRNA H. pylori-induced AUF1 expression was associated with p-ERK activation and CagA. Furthermore, knockdown of AUF1 significantly inhibited cell viability, migration ability, and arrested fewer cells in S-phase., Conclusion: Our data demonstrated that H. pylori infection downregulated GKN1 expression via the CagA/p-ERK/AUF1 pathway. AUF1 promoted gastric cancer at least partly through downregulating GKN1, which presented a novel potential target for the treatment of gastric cancer., (© 2019 John Wiley & Sons Ltd.)

CHFR is a tumor suppressor that not only recognizes poly(ADP-ribosylation) (PARylation) signals at the sites of DNA damage but also is downregulated in many types of cancer. However, the underlying mechanism linking its role in PARylation-mediated DNA damage repair and tumor suppression is unclear. Here, we examined a panel of gastric cancer cell lines as well as primary tissue samples from gastric cancer patients, and found that CHFR expression was silenced by DNA hypermethylation in gastric cancer including 38.46% of primary gastric cancers. DNMT1 was associated with aberrant methylation of CHFR, and the expression of CHFR was restored by DNMT1 inhibitor 5-aza-2-deoxycytidine (5-aza-CdR) treatment. Moreover, we found that loss of CHFR abolished DNA damage repair and sensitized gastric tumor cells to PARP inhibitor treatment. Thus, our study reveals a potential therapeutic approach for treating gastric cancer with PARP inhibitor and lacking CHFR can serve as a biomarker for predicting the efficacy of PARP inhibitor on the gastric tumor treatment in future., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: For thin women with little subcutaneous fat and micromastia, they could not obtain ideal results by choosing autologous fat breast augmentation or prosthesis-only breast augmentation. To address these problems, we combined autologous fat and prosthesis for breast augmentation, and the clinical results were satisfactory., Methods: Eleven cases of composite breast augmentation from 2014 to 2017 were analyzed retrospectively. Postoperative follow-up and evaluation were completed. The operations were performed through a subaxillary incision, and the round, high-convex breast prostheses were implanted into the retropectoralis major space. Autologous fat was injected into subcutaneous, retromammary, and prepectoralis layers to cover the whole breast before and after implanting the prosthesis., Results: The mean follow-up period was 16 months (range, 6-36 months). All patients were satisfied with the size of their breasts. Postoperative complications such as infection, vascular embolism, delayed healing incision, hematoma, and seroma were not detected. In 1 case, the sensation of a unilateral nipple-areola was decreased initially but recovered after 4 months. Long-term complications such as capsular contracture, palpable nodules, double-bubble deformity, asymmetry, poor handling, implant edge visibility, and palpability also did not occur., Conclusion: Breast augmentation combining autologous fat and prosthesis was safe and could achieve aesthetically satisfactory results.

Goals: The main aim of this study was to investigate the significance of a pale area via flexible spectral imaging color enhancement (FICE) in the diagnosis of esophageal dysplasia and cancer., Background: The early diagnosis of esophageal squamous cancer is challenging, and the indication of Lugol's chromoendoscopy has not yet been well established., Study: The esophageal mucosa of patients at our endoscopic center were sequentially evaluated with white-light endoscopy and FICE during insertion of the endoscope, followed by staining with Lugol's solution during withdrawal. Patients were divided into 2 groups depending on whether esophageal leukoplakia was detected by white-light endoscopy and 2 groups depending on whether a pale area was detected by FICE. We compared cases of patients with abnormal iodine staining, and cases of dysplasia or cancer in esophageal leukoplakia-or pale area-positive and negative groups., Results: Cases of abnormal staining in the esophageal leukoplakia-or pale area-positive group were far more numerous than cases without esophageal leukoplakia or pale area, respectively (P=0.000). Cases of esophageal dysplasia and cancer in the esophageal leukoplakia-or pale area-positive group were far more numerous than cases without esophageal leukoplakia or pale area, respectively (P=0.000)., Conclusions: Iodine staining should be performed in patients with esophageal leukoplakia or pale areas. Esophageal dysplasia and early-stage cancer were more easily detected in those with esophageal leukoplakia or pale areas.

Background: Schizochytrium sp. is a marine fungus with great potential as an alternative commercial source of lipids rich in polyunsaturated fatty acids (PUFAs). To further increase lipid accumulation in Schizochytrium sp., the effect of exogenous additives has become one of the hotspots of current research. Although benzoic acid derivatives showed positive effects on lipid accumulation in Schizochytrium , the biochemical mechanism needs further investigation., Results: Four benzoic acid derivatives (sodium benzoate, p -aminobenzoic acid, p -methyl benzoic acid and folic acid) were screened and evaluated for their effect on lipid accumulation in Schizochytrium limacinum SR21. The lipid yield was increased by 56.84% with p -aminobenzoic acid ( p -ABA) at a concentration of 200 mg/L among the four tested chemical modulators. The metabolomics analysis showed that 200 mg/L p -ABA was optimal for promoting glucose catabolism in glycolysis with an increase in the mevalonate pathway and a weakening of the tricarboxylic acid (TCA) cycle. Moreover, p -ABA increased NADPH generation by enhancing the pentose phosphate pathway (PPP), ultimately redirecting the metabolic flux to lipid synthesis. Fed-batch fermentation further proved that p -ABA could significantly increase the yield of lipid by 30.01%, reaching 99.67 g/L, and the lipid content was increased by 35.03%, reaching 71.12%. More importantly, the yields of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were increased by 33.28% and 42.0%, respectively., Conclusion: The addition of p -ABA could promote the synthesis of tetrahydrofolate, enhancing NADPH, which ultimately promoted the flow of carbon flux to lipid synthesis. These findings provide a valuable strategy for improving the lipid accumulation in Schizochytrium by additives., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: Mutations in the surfactant protein C gene (SFTPC) result in interstitial lung disease (ILD). Our objective was to characterize clinical and genetic spectrum of ILD in Chinese children associated with SFTPC mutations., Methods: Six Chinese children with ILD heterozygous for SFTPC mutations were included. Candidate genes responsible for surfactant dysfunction were sequenced by next-generation sequencing. Subclones of SFTPC with novel mutations were generated and transiently transfected into A549 cells. The functional characterization of mutant surfactant protein C (SP-C) was evaluated by Western blotting and immunofluorescence., Results: The age of onset ranged from 7 days to 15 months. All cases required supplemental oxygen. Failure to thrive (5/6) was the most significant extra-pulmonary manifestation. Hydroxychloroquine was given as the long-term treatment of lung disease in four patients and two of them responded well. Three mutations were identified in six patients: four with I73T, one with D105G, one with Y113H. Mutations in three patients were inherited and three arised de novo. Western blotting revealed totally different band patterns between mutant SP-C (D105G and Y113H) and the wildtype. Immunofluorescence showed mutant SP-C (D105G) was scarcely trafficked to lamellar bodies but localized well to early endosomes, which was in marked contrast to the wildtype protein., Conclusion: SFTPC mutations were an important cause of childhood ILD in Chinese population. I73T was a common SFTPC mutation in Chinese ILD children associated with surfactant protein C mutations.

Gastric cancer is an important cause of death worldwide with Helicobacter pylori (H. pylori) considered a leading and known risk factor for its development. More particularly and despite the underlying mechanisms not being very clear, studies have revealed that the H. pylori cytotoxin-associated gene A (CagA) protein plays a key role in this process. In this study it was found that H. pylori increased the expression of miR-543 in human gastric cancer tissue when compared with H. pylori-negative gastric cancer tissue samples. In vitro experiments showed that increased expression of miR-543 induced by CagA is a strong promoter of cell proliferation, migration, and invasion. Conversely, a miR-543 inhibitor suppressed or reversed these effects. It was furthermore found that silencing miR-543 inhibited autophagy and led to epithelial-mesenchymal transition (EMT) under in vitro. The mechanisms by which miR-543 targets SIRT1 to downregulate autophagy was also described. The results suggest that in the progression of H. pylori-associated gastric cancer, CagA induces overexpression of miR-543, which subsequently targets SIRT1 to suppress autophagy. This may be followed by increased expression of EMT causing cell migration and invasion. Consequently, miR-543 might be considered a therapeutic target for H. pylori-associated gastric cancer.

Background and Objective: Gastric cancer is one of the most common cancers worldwide. However, the mechanisms associated with this disease are still not clear. Malic enzyme 1 (ME1) is a metabolic enzyme that is overexpressed in various cancers. Here, we examined whether it is involved in gastric cancer., Methods: ME1 expression was knocked down in the gastric cancer cell line SGC7901. Cell growth and migration were measured using a real-time microelectronic cell sensor system. Cell invasion was measured using a Transwell assay. Cell cycle analysis was also performed to examine cell cycle arrest. A gastric cancer tissue microarray of gastric cancer was stained using immunohistochemistry. ME1 expression levels were also statistically analysed., Results: ME1 knockdown in gastric cancer SGC7901 cells significantly inhibited cell proliferation, migration, and invasion. Cell cycle arrest was induced in the G2 phase. Further, ME1 expression was significantly correlated with gastric cancer patient prognosis based on both univariable and multivariable survival analysis. No significant difference was found between ME1 expression in gastric cancer tissues and that in adjacent tissues., Conclusion: Our results provide evidence that ME1 is a key factor for gastric cancer. ME1 might be pro-oncogenic during both the development and migration of gastric cancer; it also might be related to gastric cancer patient survival., Competing Interests: The authors report no conflicts of interest in this work.

Background: Gastric cancer is still a common cancer worldwide. Investigation of potential plasma biomarkers for gastric cancer diagnosis is essential for prevention strategies and early intervention for gastric cancer-control planning., Objectives: This study was aimed to explore the lncRNAs' promoter of CDKN1A antisense DNA-damage-activated RNA (PANDAR), FOXD2-AS1, and SMARCC2 as potential novel diagnostic biomarkers for gastric cancer., Method: 109 gastric cancer patients and 106 healthy controls were involved in this study. Plasma lncRNAs PANDAR, FOXD2-AS1, and SMARCC2 were detected by real-time PCR. Student's t -test, Mann-Whitney U test, and Chi-square test were used to verify the differences of clinical variables between two groups. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of every biomarker. Multivariable analysis of risk factors for gastric cancer was performed using logistic regression analysis., Results: There were significant differences in age, gender, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 153 between gastric cancer and healthy controls ( P <0.05). Compared with healthy subjects, the levels of plasma lncRNAs PANDAR, FOXD2-AS1, and SMARCC2 were all significantly higher in gastric cancer patients ( P <0.05). These lncRNAs were significantly associated with clinicopathological parameters of gastric cancer, like pathological differentiation, TNM stage, and/or lymph nodes metastasis, and/or invasion depth ( P <0.05). The AUC for lncRNA PANDAR was 0.767, for FOXD2-AS1 was 0.700, for SMARCC2 was 0.748, and the AUC of the combinative diagnostic value of these three lncRNAs was 0.839. Adjusted by other variables, these lncRNAs' expressions were significantly associated with gastric cancer., Conclusions: Plasma lncRNAs PANDAR, FOXD2-AS1, and SMARCC2 might be appropriate diagnostic biomarkers for gastric cancer., Competing Interests: The authors report no conflicts of interest in this work.

Helicobacter pylori is a major cause of gastric cancer. This study was aimed to explore the characteristic of DNA damage induced by H. pylori infection in gastric cancer AGS cells. After infection with H. pylori, the reactive oxygen species (ROS) levels in AGS cells were significantly higher than those in the uninfected cells. Cells with longer comet tails were detected after infection with H. pylori. The number of apurinic/apyrimidinic endonuclease 1- and phosphorylated H2AX-positive cells was significantly increased compared with the number of negative control cells. The expression of pChk1 and pChk2 was significantly upregulated by H. pylori infection. Cell growth was inhibited after H. pylori infection. All these results were dose dependent. The cell alterations were more significant upon infection with H. pylori at a multiplicity of infection (MOI) of 100:1 than at an MOI of 50:1. H. pylori infection can induce DNA single-strand breaks, DNA double-strand breaks, and cell cycle checkpoint activation after ROS generation in the gastric cancer cell line AGS, which is a potential driver for gastric cancer.

Neuroprotective effects of dexmedetomidine (Dex) have been reported in various models of brain injury. However, to our knowledge, the neuroprotective mechanism of Dex pretreatment in rats remains unknown. The aim of the present study was to detect the expression of the α2A adrenergic receptor (ADRA2A) in focal ischemic brain tissues and to investigate the protective role and corresponding mechanism of Dex pretreatment in cerebral ischemia in rats. A hypoxia/reoxygenation (H/R) cell model in primary cultured astrocytes and a focal cerebral ischemia/reperfusion (I/R) model in adult rats were used. The expression of ADRA2A and extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the primary cultured astrocytes and rat brain ischemic tissues was detected in the different conditions prior to and following Dex pretreatment using western blotting. The H/R model of primary cultured astrocytes and the focal cerebral I/R model in adult rats were successfully constructed. Under the normal oxygen conditions, 500 ng/ml Dex pretreatment increased the expression of ADRA2A and phosphorylated (p)-ERK1/2 in the astrocytes compared with in the control group. Hypoxic culture for 6 h and then reoxygenation for 24 h decreased the levels of p-ERK1/2 in the astrocytes compared with those in control group. This decrease was prevented by Dex pretreatment for 3 h. The hypoxic culture and then reoxygenation increased the expression of ADRA2A. Similarly, compared with those prior to Dex treatment, the levels of ADRA2A and p-ERK1/2 in the brain ischemic tissues following Dex treatment were increased. The levels of ADRA2A and p-ERK1/2 were 0.72±0.23 and 0.66±0.25 following Dex treatment, compared with 0.76±0.22 and 0.31±0.18, respectively, prior to Dex treatment. The effect of Dex pretreatment increasing p-ERK1/2 expression was attenuated by AG1478 pretreatment. In summary, Dex appeared to promote phosphorylation of ERK1/2 in astrocytes under H/R. As a specific agonist of ADRA2A, Dex may activate phosphorylation of ERK1/2 via ADRA2A in astrocytes. Thus, the neuroprotective role of Dex pretreatment against cerebral ischemic injury may function via ADRA2A-mediated phosphorylation of ERK1/2.

Schizochytrium sp. is a kind of marine microalgae with great potential as promising sustainable source of polyunsaturated fatty acids (PUFAs). Polyketide synthase-like (PKS synthase) is supposed to be one of the main ways to synthesize PUFAs in Schizochytrium sp. In order to study the exact relationship between PKS and PUFA biosynthesis, chain length factor (CLF) and dehydrogenase (DH) were cloned from the PKS gene cluster in Schizochytrium sp., then disrupted by homologous recombination. The results showed that DH- and CLF-disrupted strains had significant decreases (65.85 and 84.24%) in PUFA yield, while the saturated fatty acid (SFA) proportion in lipids was slightly increased. Meanwhile, the disruption of CLF decreased the C-22 PUFA proportion by 57.51% without effect on C-20 PUFA accumulation while DH-disrupted mutant decreased the production of each PUFA. Combined with analysis of protein prediction, it indicated that CLF gene exerted an enormous function on the carbon chain elongation in PUFA synthesis, especially for the final elongation from C-20 to C-22 PUFAs. Metabolomics analysis also suggested that the disruption of both genes resulted in the decrease of PUFAs but increase of SFAs, thus weakening glycolysis and tricarboxylic acid (TCA) cycle pathways. This study offers a broad new vision to research the mechanism of PUFA synthesis in Schizochytrium sp.

Polyunsaturated fatty acids (PUFAs) have been widely applied in the food and medical industry. In this study, malonyl-CoA: ACP transacylase (MAT) was overexpressed through homologous recombination to improve PUFA production in Schizochytrium. The results showed that the lipid and PUFA concentration were increased by 10.1 and 24.5% with MAT overexpression, respectively. Metabolomics analysis revealed that the intracellular tricarboxylic acid cycle was weakened and glucose absorption was accelerated in the engineered strain. In the mevalonate pathway, intracellular carotene content was decreased, and the carbon flux was then redirected toward PUFA synthesis. Furthermore, a glucose fed-batch fermentation was finally performed with the engineered Schizochytrium. The total lipid yield was further increased to 110.5 g/L, 39.6% higher than the wild strain. Docosahexaenoic acid and eicosapentaenoic acid yield were enhanced to 47.39 g/L and 1.65 g/L with an increase of 81.5 and 172.5%, respectively. This study provided an effective metabolic engineering strategy for industrial PUFA production.

Accessory spleen (AS) usually presents as an isolated asymptomatic mass of splenic tissue separated from the body of the actual spleen. Multiple pelvic ASs are more unusual than single pelvic AS. The present study reported on the rare case of multiple pelvic AS. A 39-year-old Chinese woman presented at our hospital with complaints of abdominal pain for one week. A large pelvic mass behind the uterus was identified on ultrasound examination. Multiple AS in the pelvis was primarily considered during the operation and confirmed by histopathological examination after the surgery. The literature in English language was also reviewed by retrieving studies on AS published over the past 30 years, and it was discussed how to diagnose and treat pelvic AS. In conclusion, to the best of our knowledge, the present study provided the first case report of multiple pelvic AS. The gynecologist should be aware of the rare possibility of an AS in patients with abdominal and pelvic complaints and/or a pelvic mass. Pelvic AS is generally determined during radiological investigations or during open or laparoscopic surgeries.

Background: To examine the effects of recombinant human endostatin combined with radiotherapy on colorectal cancer HCT-116 cell xenografts in nude mice., Methods: Forty male BALB/c nude mice were injected with human colorectal cancer HCT-116 cells to form xenografts and then randomized into the following 4 groups (each group comprised ten mice): a control group, an endostatin group (20 mg/kg endostatin once a day for 10 days), a radiotherapy group (a 6-Gy dose was administered via a 6-MV X-ray on day 5 post-inoculation), and a combination therapy group (radiotherapy with endostatin treatment). The tumor growth inhibition rate were detected. CD31, vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1α (HIF-1α) expression and microvascular density (MVD) were evaluated by immunohistochemistry. The expression of VEGF protein was also detected by western blotting., Results: The tumor growth inhibition rate in the radiotherapy with endostatin treatment group was significantly higher than those in endostatin group or radiotherapy group (77.67% vs 12.31% and 38.59%; n = 8 per group, P < 0.05). The results of immunohistochemistry showed that treatment with radiotherapy induced significant increases in CD31, VEGF, and HIF-1α expression and MVD compared with treatment with saline, while treatment with endostatin or radiotherapy with endostatin induced reductions in CD31, VEGF, and HIF-1α expression and MVD compared with treatment with saline (n = 8 per group, P < 0.05). The results of western blotting showed that VEGF protein expression in radiotherapy group was significantly increased compared with that in the control group. However, VEGF protein expression in the endostatin or radiotherapy with endostatin groups was significantly decreased compared with that in the control group (n = 8 per group, P < 0.05)., Conclusions: Endostatin combined with radiotherapy can significantly inhibit HCT-116 cell xenograft growth, possibly by inhibiting angiogenesis and attenuating tumor cell hypoxia.

Objectives: Despite varying degrees in research training, most academic clinicians are expected to conduct clinical research. The objective of this research was to understand how clinical researchers of different skill levels include variables in a case report form for their clinical research., Setting: The setting for this research was a major academic institution in Beijing, China., Participants: The target population was clinical researchers with three levels of experience, namely, limited clinical research experience, clinicians with rich clinical research experience and clinical research experts., Methods: Using a qualitative approach, we conducted 13 individual interviews (face to face) and one group interview (n=4) with clinical researchers from June to September 2016. Based on maximum variation sampling to identify researchers with three levels of research experience: eight clinicians with limited clinical research experience, five clinicians with rich clinical research experience and four clinical research experts. These 17 researchers had diverse hospital-based medical specialties and or specialisation in clinical research., Results: Our analysis yields a typology of three processes developing a case report form that varies according to research experience level. Novice clinician researchers often have an incomplete protocol or none at all, and conduct data collection and publication based on a general framework. Experienced clinician researchers include variables in the case report form based on previous experience with attention to including domains or items at risk for omission and by eliminating unnecessary variables. Expert researchers consider comprehensively in advance data collection and implementation needs and plan accordingly., Conclusion: These results illustrate increasing levels of sophistication in research planning that increase sophistication in selection for variables in the case report form. These findings suggest that novice and intermediate-level researchers could benefit by emulating the comprehensive planning procedures such as those used by expert clinical researchers., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Vibrio parahemolyticus is a devastating bacterial pathogen that often causes outbreak of vibriosis in abalone Haliotis diversicolor. Elucidation of metabolic mechanisms of abalones in responding to V. parahemolyticus infection is essential for controlling the epidemic. In this work, 1 H NMR-based metabolomic techniques along with correlation and network analyses are used to investigate characteristic metabolites, as well as corresponding disturbed pathways in hepatopancreas and gill of H. diversicolor after V. parahemolyticus infection for 48 h. Results indicate that obvious gender- and tissue-specific metabolic responses are induced. Metabolic responses in female abalones are more clearly observed than those in males, which are primarily manifested in the accumulation of branched-chain amino acids and the depletion of organic osmolytes (homarine, betaine and taurine) in the infected gills of female abalones, as well as in the depletion of glutamate, branched-chain and aromatic amino acids in the infected hepatopancreases of female abalones. Moreover, based on major metabolic functions of the characteristic metabolites, we have found that V. parahemolyticus infection not only cause the disturbance in energy metabolism, nucleotide metabolism and osmotic balance, but also induce oxidative stress, immune stress and neurotoxic effect in different tissues with various mechanisms. Our study provides details of metabolic responses of abalones to V. parahemolyticus infection and will shed light on biochemical defence mechanisms of male and female hosts against pathogen infection., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A 'two birds, one stone' strategy was developed via a one-pot click reaction to simultaneously prepare a novel cyclodextrin (CD) dimer based aggregation induced emission (AIE) sensor (AIE-DCD) and a monomer based chiral stationary phase (CSP-MCD) for chiral high performance liquid chromatography (CHPLC). AIE-DCD was found to afford satisfactory AIE response for specific detection of Zn 2+ with a detection limit of 50 nM. CSP-MCD exhibits excellent enantioseparation ability toward dansyl amino acids, where the resolution of dansyl amino leucine reaches 5.43., Competing Interests: The authors declare no conflict of interest.

Background: Variation in genes implicated in monoamine neurotransmission may interact with environmental factors to influence antidepressant response. We aimed to determine how a range of single nucleotide polymorphisms in monoaminergic genes influence this response to treatment and how they interact with childhood trauma and recent life stress in a Chinese sample. An initial study of monoaminergic coding region single nucleotide polymorphisms identified significant associations of TPH2 and HTR1B single nucleotide polymorphisms with treatment response that showed interactions with childhood and recent life stress, respectively (Xu et al., 2012)., Methods: A total of 47 further single nucleotide polymorphisms in 17 candidate monoaminergic genes were genotyped in 281 Chinese Han patients with major depressive disorder. Response to 6 weeks' antidepressant treatment was determined by change in the 17-item Hamilton Depression Rating Scale score, and previous stressful events were evaluated by the Life Events Scale and Childhood Trauma Questionnaire-Short Form., Results: Three TPH2 single nucleotide polymorphisms (rs11178998, rs7963717, and rs2171363) were significantly associated with antidepressant response in this Chinese sample, as was a haplotype in TPH2 (rs2171363 and rs1487278). One of these, rs2171363, showed a significant interaction with childhood adversity in its association with antidepressant response., Conclusions: These findings provide further evidence that variation in TPH2 is associated with antidepressant response and may also interact with childhood trauma to influence outcome of antidepressant treatment., (© The Author 2016. Published by Oxford University Press on behalf of CINP.)

Dogs play an important role in rabies transmission throughout the world. In addition to the severe human rabies situation in China, spillover of rabies virus from dogs in recent years has caused rabies outbreaks in sheep, cattle and pigs, showing that there is an increasing threat to other domestic animals. Two livestock rabies outbreaks were caused by dogs in Shanxi province, China from April to October in 2015, resulting in the deaths of 60 sheep, 10 cattle and one donkey. Brain samples from one infected bovine and the donkey were determined to be rabies virus (RABV) positive by fluorescent antibody test (FAT) and reverse transcription polymerase chain reaction (RT-PCR). The complete RABV N genes of the two field strains, together with those of two previously confirmed Shanxi dog strains, were amplified, sequenced and compared phylogenetically with published sequences of the N gene of RABV strains from Shanxi and surrounding provinces. All of the strains from Shanxi province grouped closely, sharing 99.6 %-100 % sequence identity, indicating the wide distribution and transmission of dog-mediated rabies in these areas. This is the first description of donkey rabies symptoms with phylogenetic analysis of RABVs in Shanxi province and surrounding regions. The result emphasizes the need for mandatory dog rabies vaccination and improved public education to eradicate dog rabies transmission.

Final oocyte maturation is the key step to successful spawning and fertilization. Quantitative real-time PCR (qPCR) is the technique of election to quantify the abundance of functional genes in such study. Reference gene is essential for correct interpretation of qPCR data. However, an ideal universal reference gene that is stable under all experimental circumstances has not been described. Researchers should validate their reference genes while performing qPCR analysis. The expression of 6 candidate reference genes: 18s rRNA, 28s rRNA, Cathepsin Z, Elongation factor 1-α, Glyceraldehyde-3-phosphate dehydrogenase and β-actin were investigated during final oocyte maturation induced by different compounds (DES and DEHP) in common carp (Cyprinus carpio). Four softwares (Bestkeeper, geNorm, NormFinder and RefFinder) were used to screen the most stable gene in order to evaluate their expression stability. The results revealed that EF1α was highly stable expressed when final oocyte maturation was induced by DES, while gapdh was the most stable gene when final oocyte maturation was induced by DEHP. Stable expressed reference gene selection is critical for all qPCR analysis to get accurate target gene mRNA expression information., (Copyright © 2016. Published by Elsevier B.V.)

Haliotis diversicolor is a commercially important cultured shellfish. It is also an important marine model organism for environmental science. High temperature accompanied with hypoxia frequently induces diseases or even death to abalones. In present study, (1)H NMR spectroscopy together with pattern recognition methods was used to investigate the responses of muscle and gill of H. diversicolor to thermal and hypoxic stresses. It was found that obvious gender-, time- and tissue-specific metabolic responses were induced by thermal and hypoxic stresses. In combination with the changes of H. diversicolor in physiological features, the dual-modal stresses were suggested to mainly cause the disturbance in energy metabolism and osmotic balance in muscle and gill tissues with different mechanisms. Further, the corresponding correlation networks and metabolic pathways derived from the characteristic metabolites were used to assess the major metabolic functions of these characteristic metabolites. These findings shed some lights on the metabolic influences of environmental stresses on marine organisms., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background. Pathologic duodenogastric reflux can induce or aggravate gastritis because of the presence of bile acids. Bile reflux has been generally considered to be associated with intestinal metaplasia and gastric cancer. However, the pathogenic mechanisms of the effects of bile acids on gastric mucosa are still unknown. Methods. To explore the mechanisms by which bile acids induce gastric mucosal lesions, we examined cell apoptosis in the gastric epithelial cell line GES-1 and investigated the changes in protein profiles of GES-1 cells in response to a bile acid deoxycholic acid using a proteomics approach. Changes in the profiles of the differently expressed proteins were analyzed using the DAVID and STRING programs. Results. We found apoptosis was significantly induced in GES-1 cells by deoxycholic acid. Using liquid chromatographic/tandem mass spectrometric (LC-MS/MS) methods, 134 upregulated proteins and 214 downregulated proteins were identified in the bile acid treated GES-1 cells. Bioinformatics analysis revealed the interactions and signaling networks of these differentially expressed proteins. Conclusion. These findings may improve the understanding of the molecular mechanisms underlying the pathogenicity of bile acids on gastric mucosa., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Background: Serum total bilirubin (TB) has been recognized as a potent endogenous antioxidant under physiological conditions, and serum high sensitive C reactive protein (hs-CRP) is the most commonly used marker which reflects activation of systemic inflammation in the body. The study investigated the association between these two indicators and further evaluated the anti-inflammatory effects of bilirubin and its clinical significance in impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) individuals., Methods: A group of 94 patients with T2DM, 68 persons with IGT, and 62 age and gender matched healthy control subjects were recruited. The serum TB, hs-CRP concentrations, carotid artery intima-media thickness (C-IMT), and other biochemical indicators were measured. The association between serum TB, hs-CRP concentrations, and C-IMT were investigated using Spearman's correlation test. The influence of analyzed parameters including the age, gender, serum TB, and hs-CRP, etc. in IGT and T2DM was assessed by binary logistic regression analyses., Results: The serum TB level decreased significantly in patients of IGT and T2DM (p < 0.01) and serum hs-CRP concentrations were significantly increased in IGT and T2DM (p < 0.01) compared with healthy controls. Meanwhile, the serum TB levels was negatively correlated with serum hs-CRP (P < 0.05) and C-IMT (P < 0.05) in IGT and T2DM. Logistic regression analysis showed that the serum TB was a protective factor (OR = 0.852, P = 0.045) and serum hs-CRP was a risk factor (OR = 2.010, P = 0.006) for IGT and T2DM., Conclusions: Lower serum TB is associated with enhancement of the inflammatory response in IGT and T2DM. The serum TB may play a crucial role in inflammatory by contributing to inhibit the inflammation effect.

A novel cyclodextrin intermediate, mono-2(A)-allylcarbamido-2(A)-deoxy-permethylated β-cyclodextrin, was synthesized by reacting allylamine and newly prepared mono-2(A)-azido-2(A)-deoxy-permethylated β-cyclodextrin by the Staudinger reaction and anchored onto porous silica beads by a one-pot hydrosilylation and immobilization procedure to afford a novel chiral stationary phase. This stationary phase acts as a new member of the previous chiral stationary phase series immobilized on the cyclodextrin C2 position. This stationary phase depicted enantiomeric separation abilities toward a series of bicyclic and tricyclic racemates under reversed-phase conditions. The resolutions for hesperetin and naringenin achieved on the current phase reached 3.91 and 1.11, respectively, much higher than the previous permethylated β-cyclodextrin with the linkage at the C6 position., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Patients with inflammatory bowel disease (IBD) are at risk of developing haemophagocytic lymphohistiocytosis (HLH) because of chronic systemic inflammation as well as exposure to immunosuppressive medications. The two main causes of HLH in IBD patients are infection with cytomegalovirus and Epstein-Barr virus. Patients with Crohn's disease are more susceptible to HLH than those with ulcerative colitis. The majority of cases are seen in people receiving an immunosuppressive regimen that included thiopurines.

The mechanisms underlying gut development, especially peristalsis, are widely studied topics. However, the causes of gut peristalsis-related diseases, especially Opioid-Induced Bowel Dysfunction (OIBD) disorder, have not been well defined. Therefore, our study used zebrafish, a popular model for studying both gut development and peristalsis, and DCFH-DA, a dye that clearly labels the live fish gut lumen, to characterize the formation process of gut lumen as well as the gut movement style in vivo. By applying Loperamide Hydrochloride (LH), the μ-opioid receptor-specific agonist, we established an OIBD-like zebrafish model. Our study found that acetylcholine (ACh) was a key transmitter that derepressed the phenotype induced by LH. Overall, the study showed that the antagonistic role of ACh in the LH-mediated opioid pathway was evolutionarily conserved; moreover, the OIBD-like zebrafish model will be helpful in the future dissection of the molecular pathways involved in gut lumen development and pathology.

Helicobacter pylori infection is related to the development of gastric diseases. Various virulence factors are responsible for the pathogenic mechanisms of H. pylori infection. Our previous studies using two-dimensional gel electrophoresis showed that H. pylori thioredoxin-1 (Trx1) is overexpressed in gastric carcinomas. Here, we examined whether H. pylori Trx1 is a novel virulence factor associated with gastric tumorigenesis. We found that Trx1 expression in H. pylori isolated from gastric cancer tissues was significantly higher than that from tissues exhibiting gastritis. In the gastric epithelial cell line GES-1, infection of H. pylori with high Trx1 expression significantly induced cell apoptosis, decreased the expression of cyclin D1 and upregulated p21. However, in the gastric cancer cell line BGC823, high Trx1 expression in H. pylori significantly increased cell proliferation, and upregulated cyclin D1. The effects on cell lines were confirmed using the H. pylori Trx1-knockout mutant strain. Our observations indicate that high Trx1 expression in H. pylori is associated with gastric carcinogenesis. In H. pylori, Trx1 likely participates in the pathogenesis of gastric cancer and H. pylori expressing high levels of Trx1 would be expected to be highly pathogenic in gastric diseases in China.

Aim: To investigate the role of genetic polymorphisms in glutamatergic and GABAergic genes and their interactions with environmental stressors in antidepressant response., Methods: A set of 114 SNPs of 34 glutamatergic and GABAergic genes, mainly in promoter and coding regions, were genotyped in 281 Chinese Han major depressive disorder patients. The 17-item Hamilton Depression Rating Scale was used to evaluate the symptom severity and therapeutic efficacy. Childhood Trauma Questionnaire and Life Events Scale were used for assessing early-onset and recent stressful life events, respectively., Results: The single SNPs rs1954787 (GRIK4), rs1992647 (GABRA6), rs10036156 (GABRP) and rs3810651 (GABRQ) were significantly associated with antidepressant response, as were haplotypes in GRIK4 and GABRP genes. A genetic interaction between rs11542313 (GAD1), rs13303344 (GABRD) and rs2256882 (GABRE) was identified as impacting therapeutic response. SNPs in GRIA3 demonstrated interactions with early-onset adverse events and recent negative life stress that influence treatment outcome., Conclusion: Genetic polymorphisms in the glutamatergic and GABAergic systems and certain genetic interactions, as well as gene-environment interactions, are associated with antidepressant response.

Variation in genes implicated in serotonin neurotransmission may interact with environmental factors to influence antidepressant response. We aimed to determine how a range of polymorphisms in serotonergic genes determine this response to treatment and how they interact with childhood trauma and recent life stress in a Chinese sample. In total, 14 single nucleotide polymorphisms (SNPs) in coding regions of 10 serotonergic genes (HTR1A, HTR1B, HTR1D, HTR2A, HTR3A, HTR3C, HTR3D, HTR3E, HTR5A and TPH2) were genotyped in 308 Chinese Han patients with major depressive disorder. Response to 6 weeks' antidepressant treatment was determined by change in the 17-item Hamilton Depression Rating Scale (HDRS-17) score, and previous stressful events were evaluated by the Life Events Scale (LES) and Childhood Trauma Questionnaire-Short Form (CTQ-SF). Two 5-HT1B receptor SNPs (rs6296 and rs6298) and one tryptophan hydroxylase2 (rs7305115) SNP were significantly associated with antidepressant response in this Chinese sample, as was a haplotype in TPH2 (rs7305115 and rs4290270). A gene-gene interaction on antidepressant response was found between SNPs in HTR1B, HTR3A and HTR5A in female subjects. The HTR1B SNPs demonstrated interaction with recent stress, while that for TPH2 interacted with childhood trauma to influence antidepressant response.

Objective: Antidepressant effects on monoamine neurotransmission may be influenced by genetic variation in intracellular signal transduction pathways, such as the cyclic adenosine monophosphate (cAMP)--protein kinase A (PKA) pathway, Ras-mitogen activated protein kinase (MAPK) pathway and calcium/calmodulin-dependent protein kinase (CaMK) pathway. The aims of this study were to examine the association of polymorphisms in candidate genes of these three signal transduction pathways with response to antidepressant treatment, and to determine the effects of, and interactions with, environment factors., Methods: We recruited 412 patients who met diagnosis criteria for major depressive disorder (MDD) (DSM-IV Axis I). 284 patients completed 8 weeks treatment with selective serotonin reuptake inhibitors (SSRIs) or serotonin and noradrenergic reuptake inhibitors (SNRIs). Severity of depression was measured with the Hamilton Depression Rating Scale (HDRS) before and after 8 weeks antidepressant treatment. 209 patients completed the Childhood Trauma Questionnaire, 28 item Short Form (CTQ-SF) which was used to evaluate childhood adverse events. 218 patients completed the Life Events Scale (LES) which were used to evaluate life stress before onset. 155 SNPs in 66 candidate genes were genotyping by Illumina GoldenGate, including 28 SNPs in 15 genes of cAMP-PKA pathway, 37 SNPs in 17 genes of Ras-MAPK pathway and 90 SNPs in 34 genes of CaMK pathway. The remission criterion was HDRS score equal to or less than 7. Single SNP and haplotype associations were analyzed by UNPHASED 3.3.13. Gene-environment interactions were analyzed by binary logistic regression with SPSS 11.0 software., Results: The rs2230372 SNP in ITPR2, rs2280272 in PRKCZ, rs17109671, and rs17109674 in PLCE1 were significant associated with remission, as were haplotypes in PRKCZ and PLCE1. All these positive associations were found in genes of the CaMK pathway, but not the cAMP-PKA or Ras-MAPK pathways. There were no significant differences in CTQ scores and LES scores between remitters and non-remitters. No significantly interactions between candidate genes and environment effects were observed., Conclusion: The CaMK pathway may be important in determining antidepressant response. But recent adverse life events, childhood adversity, and interactions between candidate genes and environment factors appear not to influence short term antidepressant outcome., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)

Background: Catecholamine neurotransmission plays an important role in major depression. Variation in genes implicated in the synthesis and signal transduction of catecholamines (norepinephrine and dopamine) may interact with environmental factors to affect the outcome of antidepressant treatment. We aimed to determine how a range of polymorphisms in noradrenergic and dopaminergic genes influence this response to treatment and how they interact with childhood trauma and recent life stress in a Chinese sample., Methods: In a sample of 308 Chinese Han patients with major depressive disorder, 13 single nucleotide polymorphisms (SNPs) in coding regions of six genes (MAOA, SLC6A2, TH, COMT, DRD2, DRD3) with minor allele frequencies >5% were successfully genotyped from an initial series of 35 SNPs in 11 candidate genes associated with catecholamine neurotransmission. The responses to 6 weeks' treatment with antidepressant drugs was determined by changes in the 17-item Hamilton Depression Rating Scale (HAMD-17) score, and previous stressful events were evaluated by the Life Events Scale (LES) and Childhood Trauma Questionnaire-Short Form (CTQ-SF). Single SNP and haplotype associations with treatment response were analysed by UNPHASED 3.0.13, gene-gene interactions were analysed by generalized multifactor dimensionality reduction (GMDR) and gene-environment interactions by logistic regression., Results: A haplotype in MAOA (rs1137070 and rs6323) was significantly associated with antidepressant response in the total group, the nonSSRI subgroup and the female subgroup. Two haplotypes in COMT (involving rs4633, rs4818 and rs769224) were significantly associated with antidepressant response in the nonSSRI subgroup. The SLC6A2 SNPs interacted with childhood trauma to influence antidepressant response., Conclusions: A haplotype in MAOA and two haplotypes in COMT are found to be associated with antidepressant treatment response in this sample. Stressors in early life may interact with polymorphisms in SLC6A2 to influence response to antidepressant treatment., (Copyright © 2011. Published by Elsevier B.V.)

The oncogene Bmi-1 is highly up-regulated in breast carcinoma and is found to be efficient in preventing apoptosis of the cancer cells. Doxorubicin is an important chemotherapeutic agent against breast carcinoma. However, the effective therapeutic response to doxorubicin is often associated with severe toxicity. The present study is targetted at developing a strategy to increase doxorubicin sensitivity to lower doses without compromising its efficacy. A stable cell line with a persistent silencing of Bmi-1 was established. MTT assay was performed to evaluate 50% inhibitory concentration (IC50) values of doxorubicin. Apoptosis was detected by FCM and the expression of related genes [phosphor-Akt (pAkt), totle-Akt (tAkt), Bcl-2 and Bax] was studied by Western blot. In vivo, the sensitivity of the tumor tissues against doxorubicin was evaluated by transplanted MCF-7 nude mice model and the apoptosis of tissue cells was detected by TUNEL assay. The expression of pAkt and Bcl-2 was down-regulated, whereas Bax was up-regulated in Bmi-1 silencing cells. The results obtained indicated that silencing of Bmi-1 can render MCF-7 cells more sensitive to doxorubicin which induced a significantly higher percentage of apoptosis cells in vitro and in vivo. All together these results clearly demonstrate that Bmi-1 siliencing combined treatment of doxorubicin might be a new strategy for biological treatment on breast cancer.

The combined application of laser capture microdissection (LCM) and gene expression microarray analysis has rarely been used to study lymphangiogenesis because of technical obstacles. In this study, a novel method using this combined approach was developed to analyze the gene expression patterns in lymphatic endothelial cells (LECs). First, LECs were identified in frozen sections using rapid immunostaining and isolated using LCM, and then intact RNA from the LECS was purified and amplified. The expression profile was analyzed using microarray analysis, and the expression of selected genes (Sema4C and C4orf7) was evaluated by quantitative RT-PCR (qRT-PCR) and immunofluorescence assays. These results indicate that the combination of RIHC-LCM, two-round linear amplification of the small sample RNA and genome-wide microarray analysis allows gene expression profiling of tumor LECs, which provides a powerful tool for the study of molecular details in human lymphangiogenesis-related diseases, such as lymphatic metastasis of human breast cancers. These findings also suggest that the LEC-specific genes Sema4C and C4orf7 may play an important role in the oncogenesis of human breast cancer.

Aims: Studies in the recent decade have shown that brain-derived neurotrophic factor (BDNF) may play an important role in the pathogenesis of major depressive disorder (MDD). Tissue-type plasminogen activator (tPA) has been implicated in the control of the direction of BDNF action. The aim of the study was therefore to investigate the changes of BDNF/tPA levels and their clinical meanings in geriatric depression., Methods: Plasma BDNF and tPA levels were measured in late-onset geriatric depression (LGD) before treatment (n = 24) and after 6 weeks of antidepressant treatment (n = 24) compared with control subjects (n = 30) using enzyme-linked immunosorbent assay. The severity of depression was assessed with the Hamilton Depression Rating Scale., Results: Baseline plasma BDNF and tPA levels were significantly lower in LGD patients compared to controls (P = 0.037 and P = 0.000, respectively). There was a heightening tendency of plasma BDNF level after treatment., Conclusions: Plasma BDNF and tPA levels are associated with LGD. The complex mechanism of BDNF and tPA in LGD should be further explored in future studies.

Background: Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been suggested to be associated with major depressive disorder (MDD). There were a few reports of the relationship between the variant and late-onset depression (LOD) in Chinese Han population., Objective: To investigate the relationship among BDNF Val66Met gene variants, BDNF plasma level and LOD., Methods: Chinese Han patients with LOD (n = 99) and control subjects (n = 110) were assessed for BDNF Val66Met gene polymorphism. BDNF plasma level was tested only in LOD., Results: There were no significant differences in genotypes and allele frequencies between cases and controls (p = 0.744 and p = 0.845, respectively). Plasma BDNF level also did not show significant differences in three genotypes in LOD (p = 0.860)., Conclusion: The Val66Met polymorphism in BDNF gene may not confer susceptibility to LOD in Chinese Han population.

Membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14) plays crucial roles in tumor cell growth, invasion, and angiogenesis. To clarify whether the endogenously expressed MT1-MMP in metastatic human ovarian carcinoma cell lines SKOV3 plays a critical role in tumor cell invasiveness, antisense MT1-MMP cloned in eukaryotic expression vector pMMP14as was transferred into SKOV3 cells. 48h after transfection, decreased expression of endogenous MT1-MMP protein was detected in pMMP14as-transfected SKOV3 cells and the activation of pro-MMP2 was inhibited markedly. The mean percentage of invasive cells was (62.50 +/- 5.30) % in pMMP14as-transfected cells, which was obviously less than that (97.20 +/- 6.90) % in the control. Thus, antisense MT1-MMP effectively inhibited the endogenous MT1-MMP expression and the invasiveness in SKOV3 cells, suggesting that MT1-MMP may be a therapeutic target molecule for human invasive ovarian cancers.