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Based on the butterfly pattern structure and the star-shaped honeycomb structure, a novel auxetic butterfly-shaped honeycomb structure (BSH) was constructed, which realized the coupling improvement of negative Poisson’s ratio and in-plane stiffness. Under uniaxial tension, the equivalent elastic modulus and Poisson's ratio of the BSH structure were derived by the energy method. The relationship between Poisson's ratio and structural parameters of the BSH structure was discussed to optimize the structural parameters by numerical analysis. Poisson’s ratio and relative elastic modulus were taken as the objective function groups. The Pareto solution set was obtained by the Gamultiobj multi-objective genetic algorithm method. The Pareto solution set was sorted based on the entropy-weight TOPSIS method, and the optimal solution was selected as the solution of the novel structure optimization design. The correctness of the theoretical results was verified by the finite element analysis and experiment results. Furthermore, compared with the traditional re-entrant hexagonal honeycomb structure and the star-shaped honeycomb structure, the relative elastic modulus and auxetic effect of the BSH structure were greatly improved, and the stiffness of the novel structure was improved while maintaining a high auxetic effect.

Background: Low back pain during pregnancy can affect the daily living activities of pregnant women to a certain extent, and even lead to fetal agitation and threatened abortion. Kinesio taping (KT) can improve tissue circulation and provide elastic supports, which is a reliable method to treat low back pain. At present, there is a lack of high-level clinical evidence for the treatment of low back pain during pregnancy with KT. Therefore, this study will systematically review and analyze currently available randomized controlled trials to evaluate the efficacy and safety of KT in the treatment of low back pain during pregnancy.Methods and analysis: This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. We will search the following database sources of the Randomized controlled trials: PubMed, the Cochrane Library, EMBASE, Web of Science, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure Database (CNKI), Chinese Science, and the Wanfang Database. From the establishment of the database to April 2021. Two independent investigators will conduct an electronic literature search, study selection, data extraction, and quality assessment to summarize and evaluate the efficacy of KT in the treatment of low back pain during pregnancy. and risk of bias will be assessed using the Cochrane bias risk tool. All data analysis will be conducted using Revman5.3 software.Result: This study will objectively and comprehensively evaluate the efficacy and safety of randomized controlled trials of KT for low back pain during pregnancy, and submit the results to a peer-reviewed journal for publication.Conclusion: This study will provide clinicians with the latest high-quality evidence for the use of KT in the treatment of low back pain during pregnancy.Systematic review registration: PROSPERO CRD42021250373

Review question / Objective: The purpose of this systematic review and meta-analysis was to determine the efficacy of lower extremity exoskeletons in improving gait function in patients with spinal cord injury, compared with placebo or other treatments. Condition being studied: Spinal Cord Injury (SCI) is a severely disabling disease. In the process of SCI rehabilitation treatment, improving patients' walking ability, improving their self-care ability, and enhancing patients' self-esteem is an important aspect of their return to society, which can also reduce the cost of patients, so the rehabilitation of lower limbs is very important. The lower extremity exoskeleton robot is a bionic robot designed according to the principles of robotics, mechanism, bionics, control theory, communication technology, and information processing technology, which can be worn on the lower extremity of the human body and complete specific tasks under the user's control. The purpose of this study was to evaluate the effect of the lower extremity exoskeleton on the improvement of gait function in patients with spinal cord injury.

Pulmonary fibrosis is a fatal chronic progressive respiratory disease, characterized by continuous scarring of the lung parenchyma, leading to respiratory failure and death. The incidence of PF has increased over time. There are drugs, yet, there are some limitations. Hence, it is of importance to find new therapies and new drugs to replace the treatment of pulmonary fibrosis. In recent years, there have been a great number of research reports on the treatment of traditional Chinese medicine polysaccharides in various system fields. Among them, the treatment of PF has also gained extensive attention. This review summarized the source of polysaccharides, the drug activity of traditional Chinese medicine, and the protective effects on targets of Pulmonary fibrosis. We hope it can inspire researchers to design and develop polysaccharides, serving as a reference for potential clinical therapeutic drugs.

Purpose To determine the pharmacokinetic properties and pharmacological activity of the Yougui pill (YGP), which is a well-known Chinese medicine formula. Methods An ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry via electrospray ionization interface (UPLC-ESI-MS/MS) method was developed and validated for the simultaneous determination of several components in rat plasma. The method was then successfully applied to the pharmacokinetics of six bioactive components in experimental autoimmune encephalomyelitis (EAE) model rats after oral administration of YGP. The expression of cAMP response element binding protein (CREB) and growth-associated protein-43 (GAP-43) in SH-SY5Y cells treated with these six components, YGP extract, and YGP-containing serum were investigated to determine the pharmacodyamic material basis of YGP. Six bioactive components were detected in rat plasma, including songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline and sweroside, which were rapidly absorbed after administration in EAE model rats. Results The main pharmacokinetic parameters of six bioactive components were determined, and the constituents increased CREB and GAP-43 expressions in serum-deprived SH-SY5Y cells. The YGP-containing serum, six bioactive components, and YGP extract significantly increased the expression of both CREB and GAP-43 (P

The impact of antiviral therapy before tumorigenesis on microvascular invasion (MVI) of Chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) is still unknown. In this retrospective cohort study 3,276 HCC patients with early-stage who underwent curative resection were included. We investigated the effect of precancer antiviral therapy on the pathology, especially MVI, of CHB-related HCC. MVI occurrence rates of CHB-related HCC stratified by histopathologic inflammation grades of G1, G2, and G3 were 30.4%, 34.7%, and 38.6%, respectively, compared to 19.8% for CHB-negative HCC. Patients who received standard antiviral treatment showed much lower rates of MVI, higher tumor capsule integrity, less frequent satellite micronodules and lower AFP level compared to the no antiviral group. Moreover, precancer antiviral therapy prolonged the disease-free survival (DFS), which are also proved to be independent indicators of DFS. In addition, we show that antivirals may suppress early progression of HCC primarily by inhibition of HBV viral load, and influencing the expression levels of CK18, GPC3, OPN and pERK. Hence, we demonstrate that precancer antivirals significantly reduce the MVI rate of CHB-related HCC, reduce malignancy of early-stage HCC, and improve HCC prognosis. Thus, this study confirms the importance of antiviral therapy for CHB patients.

Background. Diabetic peripheral neuropathy (DPN) is a common complication of diabetes but its pathogenesis is not fully clarified. Endoplasmic reticulum (ER) stress has been confirmed to be involved in the development of DPN. Dorsal root ganglion neuron (DRGn) is the target cell of DPN injure in the peripheral neurons system. Schwann cell (SCs)-derived exosomes (SC-EXOs) can carry IRE1α signal transduction factors in ER stress to DRGn. The aim of this study is to investigate the effect of SC-EXOs treated with paeoniflorin (PF) on DRGn stimulated by high glucose. Methods. SCs were divided into Control group (Control), 150 mM glucose group (HG), high osmotic pressure group (HOP), and low, middle, and high dose PF group (PF1, PF10, and PF100). Exosomes were obtained from SCs by ultracentrifugation and identified according to marker proteins, including CD63, Alix, Hsp70, and TSG101. ER stress initiating factor GRP78, the IRE1α pathway information transmission factor IRE1α, and the phosphorylation level of IRE1α were detected by Western blot, DRGn is divided into Control group (Control), 50 mM glucose group + Control exosomes group (HG + EXOs Control), 50 mM glucose group (HG), and 50 mM glucose group + administration exosomes group (HG + EXOs PF1, HG + EXOs PF10, and HG + EXOs PF100); ER morphology of primary DRGn was observed by using the transmission electron microscope, the level of DRGn apoptosis was analyzed by TUNEL, and the downstream proteins of ER stress including CHOP, XBP1S, JNK, and p-JNK in DRG and the expression of apoptosis-related proteins Bcl-2, Bax, Caspase-3, and Caspase-12 were measured by Western blot. Results. Compared with the exosomes in the HG group, the exosomes after the intervention of PF can significantly reduce the expression of GRP78, IRE1α, and the phosphorylation level of IRE1α P < 0.05 ; compared with the DRGn in the HG group, the SC-EXOs treated with PF could regulate the expression of proteins downstream of IRE1α pathway in ER stress ( P < 0.05 or P < 0.01 ), improve the morphological integrity of ER, and reduce apoptosis in DRGn ( P < 0.05 or P < 0.01 ). Conclusion. PF regulates the information of ER stress carried by SC-EXOs and further affects downstream of IRE1α pathway in DRGn, thus reducing ER stress-induced apoptosis. PF can interfere with DPN through affecting information communication carried by EXOs between SCs and DRGn.

Purposes This study was designed to evaluate the effect of preoperative jaundice on long-term prognosis of gallbladder carcinoma (GBC) after radical resection (R0). Methods A total of 267 GBC patients who underwent R0 resection from January 2004 to December 2014 were enrolled, including 54 patients with preoperative jaundice and 213 patients without jaundice. The clinicopathological parameters between the two groups were compared, and the correlation between preoperative jaundice and the long-term prognosis was furtherly analyzed. Results Unilateral and multivariate analyses of 267 GBC patients showed that the depth of tumor invasion (pT stage), lymphatic metastasis, and hepatic invasion were independent prognostic factors. The univariate and multivariate analysis of 54 GBC patients with preoperative jaundice showed that only pT stage was an independent factor for prognosis. Furthermore, the intraoperative blood transfusion and pT stage were significant different between long-term survival (survive for more than 3 years) and those who died within 3 years (P Conclusion Preoperative jaundice was not the independent factor resulting in the poor long-term prognosis of gallbladder carcinoma after R0 resection. The pT stage was the only long-term prognostic factor in all GBC patients regardless of preoperative jaundice.

Oxygen is a vital parameter for pyrroloquinoline quinone (PQQ) biosynthesis. In this study, the effects of oxygen supply on the biosynthesis of PQQ were first investigated systematically with Hyphomicrobium denitrificans FJNU-6. Following a kinetic analysis of the specific cell growth rate (μx) and specific PQQ formation rate (μp) in 5 L benchtop fermentation systems at various oxygen supply levels ranging from 0 to 60%, a novel, two-stage oxygen supply strategy was developed for enhancing PQQ production and productivity. Moreover, the transcription of genes involved in methanol oxidation and PQQ biosynthesis was analyzed throughout the process to outline the effect of oxygen supply on cell metabolism. Furthermore, with constant feeding of methanol at 0-1 g/L after the initial methanol was consumed completely, the PQQ concentration and productivity reached 1070 mg/L and 7.64 mg/L/h, respectively, after 140 h in a 5-L fermenter. The two-stage oxygen supply strategy developed in this study provides an effective and economical strategy for the industrial production of PQQ.Key Points• A novel, two-stage oxygen supply strategy was developed for enhancing PQQ production and productivity.•The transcription of genes involved in methanol oxidation and PQQ biosynthesis was regulated by changes in oxygen supply.• This study offers an effective and economical strategy for industrial or large-scale production of PQQ.

Gamma-aminobutyric acid (GABA) can be converted into 2-pyrrolidone, an intermediate in the synthesis of nylon 4 and agrochemicals, which has great potential for application in the chemical industry. The main aim of this work was to construct a simple and efficient process for industrial production of GABA from L-glutamic acid (L-Glu) by whole-cell bioconversion. The gene encoding glutamate decarboxylase (GAD) from Lactococcus lactis FJNUGA01 was overexpressed using the most available vector in Escherichia coli, pET-28a. GABA production was enhanced by optimizing the concentration of the catalyst isopropyl-β-D-thiogalactoside (IPTG), induction temperature and induction time. After optimization, GABA production reached 98.4 g L−1 with 96 mol% conversion within 6 h was achieved by whole-cell conversion using the cells induced with 1 mmol L−1 IPTG for 12 h at 30 °C. Furthermore, when the initial concentration of L-Glu was adjusted, 204.12 g L−1 GABA with 34 g L−1 h−1 productivity was reached using 2 mol L−1 L-Glu as the substrate. During the 6 h whole-cell bioconversion process, almost all L-Glu was converted to GABA with a conversion efficiency of ∼99%. The high conversion efficiency and high productivity made the GABA purification occur downstream, and the whole process is more simple and economical for industrial application.

Background Gallbladder carcinoma (GBC) remains a highly lethal disease worldwide. MiR-552 family members promote the malignant progression of a variety of digestive system tumors, but the role of miR-552-3p in GBC has not been elucidated. miR-552-3p was predicted to target the 3'-untranslated region (3'UTR) of the mRNA for the tumor suppressor gene "repulsive guidance molecule BMP co-receptor a" (RGMA). The aim of the present study was to clarify the roles and mechanisms of miR-552-3p targeting RGMA in the malignant progression of GBC. Methods In vitro: expression of miR-552-3p was detected by real-time quantitative PCR (qRT-PCR) in tumor and non-tumor adjacent tissues (NATs). Lentivirus-miR-552-3p was employed to knockdown this miRNA in GBC cell lines. Stem cell-related transcription factors and markers were assessed by qRT-PCR. Cell Counting Kit-8 (CCK-8), sphere formation and transwell assays were used to determine the malignant phenotypes of GBC cells. Targeting the 3'UTR of RGMA by miR-552-3p was verified by integrated analysis including bioinformatics prediction, luciferase assays, measures of changes of gene expression and rescue experiments. In vivo: mouse models of subcutaneous tumors and lung metastases were established to observe the effect of miR-552-3p on tumorigenesis and organ metastasis, respectively. Results MiR-552-3p was abnormally highly expressed in GBC tissues and cancer stem cells. Interference with miR-552-3p in SGC-996 and GBC-SD cells significantly inhibited GBC stem cell expansion. Reciprocally, miR-552-3p promoted GBC cell proliferation, migration and invasion both in vitro and in vivo; hence, interference with this miRNA impeded the malignant progression of GBC. Furthermore, the important tumor suppressor gene RGMA was identified as a target of miR-552-3p. The effects of miR-552-3p on cell proliferation and metastasis were abrogated or enhanced by gain or loss of RGMA function, respectively. Mechanistically, miR-552-3p promoted GBC progression by reactivating the Akt/β-catenin pathway and epithelial-mesenchymal transformation (EMT). Clinically, miR-552-3p correlated with multi-malignant characteristics of GBC and acted as a prognostic marker for GBC outcome. Conclusions MiR-552-3p promotes the malignant progression of GBC by inhibiting the mRNA of the tumor suppressor gene RGMA, resulting in reactivation of the Akt/β-catenin signaling pathway.

The aim of this study was to determine whether a combination of the tumour markers carcinoembryonic (CEA) and carbohydrate antigen 19-9 (CA19-9) would be helpful in predicting the prognosis of patients with gallbladder carcinoma (GBC) who underwent resection.A retrospective analysis of clinico-pathological features and survival of 390 patients with GBC who were treated between January 2003 and December 2013. Time-dependent receiver operating characteristic (ROC) was used to evaluate the prognostic ability of tumour markers. Combinations of preoperative CEA and CA19-9 were tested as potential prognostic factors.The evaluation of preoperative CEA and CA19-9 showed that patients with both tumour markers within the normal range had the best prognosis with a median survival of 27 months and R0 rate of 86%. Patients with both tumour markers elevated had the poorest prognosis and lower R0 rate (p 0.001). The combination of CEA and CA19-9 was an independent risk factor for overall survival. The AUROC at 5 years of combination of CEA and CA19-9 was 0.798, which was similar to CEA (0.765) or CA19-9 (0.771) alone (p = 0.103, p = 0.147).A combination of an elevated preoperative CEA and CA19-9 was associated with a worse prognosis for patients with GBC who underwent resection.

// Xin-Wei Yang 1,* , Jun-Yi Chen 2,* , Wen-Liang Yan 3,* , Jing Du 4,* , Zhi-Jian Wen 1 , Xing-Zhou Yan 1 , Ping-Hua Yang 1 , Jue Yang 1 and Bao-Hua Zhang 1 1 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China 2 Department of General Surgery, the Fourth People’s Hospital of Shanghai, Shanghai, China 3 Department of Dermatology, Jinling Hospital, Nanjing, China 4 Second Military Medical University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Bao-Hua Zhang, email: // Keywords : delayed gastric emptying, cholangitis, choledochojejunostomy, obesity, prognosis Received : August 08, 2016 Accepted : February 28, 2017 Published : March 08, 2017 Abstract The traditional, retrocolic/antegastric Roux-en-Y choledochojejunostomy is technically complicated, and the incidence of postoperative complications remains high. Here we report the outcome of 59 consecutively treated patients ( study group , SG) that underwent a new choledochojejunostomy method in which the jejunal loop is passed behind the antrum pyloricum (retrogastric route). A retrospective comparison was made between this group of patients and 187 patients ( control group , CG) that underwent conventional Roux-en-Y choledochojejunostomy (antegastric route). Baseline clinicopathological characteristics were similar in both groups, except for the BMI, which was significantly higher in the SG. The time spent on constructing the anastomosis, as well as overall postoperative complications, did not differ between groups. Compared with the CG, the incidence of postoperative delayed gastric emptying was decreased in the SG, and the time elapsed before the patients’ first postoperative liquid food consumption was shorter. We ascribe these beneficial effects to the superiority of the modified, retropyloric choledochojejunostomy approach, and propose that this surgical technique is particularly suitable for obese patients, especially those with a short ascending bowel loop.

Background: In patients with nonvalvular atrial fibrillation (NVAF), embolic stroke is thought to be associated with left atrial appendage (LAA) thrombi. The WATCHMAN LAA Occlusion Device has been shown to be noninferior to conventional oral anticoagulation with warfarin for stroke prevention in patients with NVAF. This study aimed to evaluate the procedural feasibility, safety and 12-month outcomes of the WATCHMAN LAA Occlusion Device in NVAF patients with high risk for stroke in China. Methods: The clinical data of 106 NVAF patients, who were consecutively underwent LAA closure with the WATCHMAN Device between April 2014 and May 2015, were collected. Patients were followed up at 1, 3, 6, and 12 months after discharge. A transesophageal echocardiograph was performed at 45 days after implantation and repeated in case of an unexpected event during the follow-up period. Results: This study included 106 NVAF patients with a mean age of 64.2 ± 8.6 years (ranging from 50 to 88 years), and the mean CHA 2 DS 2 -VASc score of all patients was 3.6 ± 1.6 (ranging from 2 to 9). Among those 106 NVAF patients, 100 (94.3%) patients were implanted with the device successfully. The procedural success rate was 94.3% (100/106), and the occlusion rate was 100.0% (100/100). There were one tamponade, one ischemic stroke, and eight minor pericardial effusions during hospitalization. During 12-month follow-up period, two patients developed a thrombus layer on the device that resolved with additional anticoagulation: one with visible device-thrombus experienced transient ischemic stroke, and one had a hemorrhagic stroke. There were no deaths in this study. The overall survival rate was 100.0%, and nonmajor adverse event rate was 95.0% (95/100). In this study, the expected annual rate of ischemic stroke risk in these patients according to the CHA 2 DS 2 -VASc score was 4.0%, while the observed ischemic stroke rate was 2.0% per year. Conclusions: LAA closure with the WATCHMAN Device was feasible, efficient, and safe for NVAF to prevent the accidence of stroke in Chinese patients. During the 12-month follow-up period, the observed ischemic stroke rate (2.0% per year) in our study was lower than the predicted annual stroke risk (4.0%) using the CHA 2 DS 2 -VASc score.

The impact of antiviral therapy before tumorigenesis on microvascular invasion (MVI) of Chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) is still unknown. In this retrospective cohort study 3,276 HCC patients with early-stage who underwent curative resection were included. We investigated the effect of precancer antiviral therapy on the pathology, especially MVI, of CHB-related HCC. MVI occurrence rates of CHB-related HCC stratified by histopathologic inflammation grades of G1, G2, and G3 were 30.4%, 34.7%, and 38.6%, respectively, compared to 19.8% for CHB-negative HCC. Patients who received standard antiviral treatment showed much lower rates of MVI, higher tumor capsule integrity, less frequent satellite micronodules and lower AFP level compared to the no antiviral group. Moreover, precancer antiviral therapy prolonged the disease-free survival (DFS), which are also proved to be independent indicators of DFS. In addition, we show that antivirals may suppress early progression of HCC primarily by inhibition of HBV viral load, and influencing the expression levels of CK18, GPC3, OPN and pERK. Hence, we demonstrate that precancer antivirals significantly reduce the MVI rate of CHB-related HCC, reduce malignancy of early-stage HCC, and improve HCC prognosis. Thus, this study confirms the importance of antiviral therapy for CHB patients.

Ethnopharmacological relevance Paeoniflorin (PF) is the principal bioactive component of Paeonia lactiflora Pall., which an included in Tang Luo Ning recipe, a traditional Chinese herbal medicine based on Huangqi Guizhi Wuwu decoction. PF is also widely used in Traditional Chinese Medicine for the treatment of blood-arthralgia disease including diabetic peripheral neuropathy (DPN), but its underlying molecular mechanism of neuroprotective effects is not yet well understood. Diabetic hyperglycemia induced oxidative stress in Schwann cells, an important component of the peripheral nervous system, has been proposed as a unifying mechanism for DPN. The objective of this study is to determine the effects of PF on Schwann cells oxidative stress and apoptosis induced by high glucose. Materials and methods RSC96 cells, a Schwann cell line, were treated with high glucose (150 mM) and PF (1, 10 and 100 μM). Subsequently, MTT assay was performed. The level of apoptosis was examined by flow cytometry and the oxidative stress was reflected by reactive oxygen species (ROS), malondialdehyde (MDA), glutathione S-transferases (GST) and glutathione peroxidase (GPX) levels. The mRNA expressions of Nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were detected by qRT-PCR. The levels of Kelch-like ECH-associating protein 1 (Keap1), Nrf2, HO-1, γ-glutamylcysteine synthetase (γGCS), B-cell CLL/lymphoma 2 (Bcl-2), Bax and Caspase 3 were detected by High content analysis and/or Western blot. Results The role of PF markedly suppressed high glucose induced Schwann cells oxidative stress by decreasing ROS and MDA levels and increasing GST and GPX activity. Western blot analysis showed that PF induced nuclear translocation of Nrf2. High content analysis showed that PF promoted Nrf2 dissociation from Keap1 and upregulating the Nrf2/ antioxidant response element (ARE) pathway. Furthermore, PF reduced Schwann cells apoptosis by increasing Bcl-2 and inhibiting Bax and Caspase-3 expressions. Conclusions PF in the management of Schwann cells oxidative stress induced by high glucose may be associated with activation of Nrf2/ARE pathway and Bcl-2-related apoptotic pathway.

Clinical data shows that antitumor treatments are often ineffective if tumor cells have metastasized. To gain an effective antitumor therapeutic effect, in this report, the tumor cell was limited to the primary site and simultaneously ablated by chemotherapy. Considering the extremely complicated process of cancer metastasis, we seek to comprehensively suppress tumor metastases at both micro and macro levels, which closely link to migration and interact with each other. At the micro level, the motility of the tumor cell was decreased via accelerating mitochondria fusion. At the macro level, the unfavorable hypoxia environment was improved. A liposome-based multifunctional nanomedicine was designed by coloading latrunculin B (LAT-B), an inhibitor of actin polymerization, and doxorubicin (DOX) into the hydrophobic bilayers and aqueous cavity, respectively. Meanwhile, an oxygen reservoir named perfluoropentane (PFP) was encapsulated into the liposome core to fulfill synergistic treatment of metastatic tumors. In this paper, we demonstrated that the metastasis of the tumor cell could be effectively inhibited by LAT-B through promoting mitochondria fusion without affecting its function, making it as an encouraging candidate for effective anti-metastasis therapy. Meanwhile, we found that the combination of LAT-B and DOX shows a synergistic effect against tumors because the combined effect of these two drugs cover the entire cell proliferation process. In a word, this report presents a potential improvement in the treatment of metastatic cancer.

Background Compound kushen injection is increasingly used to treat various cancers. However, its role in the management of multiple myeloma (MM) is still controversial and requires further clarification. The aim of this study is to evaluate efficacy and safety of compound kushen injection for MM through systematic review and meta-analysis. Methods We are going to search the 6 electronic databases: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wangfang and Chinese Biomedical Literature Database. General characteristics and Specific trial characteristics will be collected from the included studies. The outcomes included overall response rate, complete response rate, 3-year progression-free survival rate, 3-year overall survival rate, and different types of treatment-related adverse events. We calculated the risk ratios as well as their 95% confidence intervals of these outcomes and pooled the results through RevMan 5.2 software. Discussion The results of the study will be submitted to a peer-reviewed journal for publication. Ethics and dissemination This study is not a clinical study, ethical approval is not required.

There is not yet a consensus regarding a difference in prognosis for patients with hepatocellular carcinoma (HCC) with and without bile duct invasion (BDI). The present study aimed to clarify the prognostic importance of BDI on the short and long-term outcome of patients with HCC who underwent surgical resection. The present study evaluated HCC with BDI, including peripheral microscopic biliary invasion and revealed that the prognosis of patients with BDI was poorer compared with those without BDI. It should be noted that peripheral BDI also had a negative impact on the prognosis of patients with HCC. The clinical prognosis assessment revealed that BDI should be considered when assigning a disease stage. BDI, either macroscopic or microscopic, indicated a poor prognosis in patients with HCC who underwent curative resection, however it was not a surgical contraindication. Macroscopic BDI and hyperbilirubinemia were significantly associated with a dismal prognosis, which should alert surgeons.

Diabetic peripheral neuropathy (DPN) is mainly characterized by demyelination resulted from the apoptosis of the Schwann cell (SCs). Although the exact mechanisms underlying DPN remain unclear, endoplasmic reticulum (ER) stress is strongly implicated in the apoptosis. Under ER stress, activated inositol-requiring kinase 1α (IRE1α) unregulated CHOP, phosphorylated JNK and Caspase-12 to aggravate apoptosis-mediated damage of DPN. Therefore, we tested the hypothesis that inhibition of IRE1α could reduce the ER stress-related apoptosis to relieve DPN. Here, we show that IRE1α siRNA improved the neurological morphology and function of DPN rats and rescued ER stress-related apoptosis in the sciatic nerve. Additionally, RSC96 cells transfected with IRE1α siRNA were used as in vitro model of DPN. It was found that IRE1α siRNA also decreased high glucose-induced apoptosis and inhibited ER stress-related apoptosis in the cells. Altogether, our results suggest that IRE1α should be considered a potential therapeutic agent for DPN.

A low-temperature-inducible protein expression vector (pSW2) based on a filamentous phage (SW1) of the deep-sea bacterium Shewanella piezotolerans WP3 was constructed. This vector replicated stably in Escherichia coli and Shewanella species, and its copy number increased at low temperatures. The pSW2 vector can be utilized as a complementation plasmid in WP3, and it can also be used for the production of complex cytochromes with multiple heme groups, which has the potential for application for metal ion recovery or bioremediation. Promoters of low-temperature-inducible genes in WP3 were fused into the vector to construct a series of vectors for enhancing protein expression at low temperature. The maximum green fluorescent protein intensity was obtained when the promoter for the hfq gene was used. The WP3/pSW2 system can efficiently produce a patatin-like protein (PLP) from a metagenomic library that tends to form inclusion bodies in E. coli . The yields of PLP in the soluble fraction were 8.3 mg/liter and 4.7 mg/liter of culture at 4°C and 20°C, respectively. Moreover, the pSW2 vector can be broadly utilized in other Shewanella species, such as S. oneidensis and S. psychrophila .

We previously developed a gamma-amino butyric acid (GABA)-producing strain of Escherichia coli, leading to production of 614.15 g/L GABA at 45 °C from L-glutamic acid (L-Glu) with a productivity of 40.94 g/L/h by three successive whole-cell conversion cycles. However, the increase in pH caused by the accumulation of GABA resulted in inactivation of the biocatalyst and consequently led to relatively lower productivity. In this study, by overcoming the major problem associated with the increase in pH during the production process, a more efficient biocatalyst was obtained through cascade modifications of the previously reported E. coli strain. First, we introduced four amino acid mutations to the codon-optimized GadB protein from Lactococcus lactis to shift its decarboxylation activity toward a neutral pH, resulting in 306.65 g/L of GABA with 99.14 mol% conversion yield and 69.8% increase in GABA productivity. Second, we promoted transportation of L-Glu and GABA by removing the genomic region encoding the C-plug of GadC (a glutamate/GABA antiporter) to allow its transport path to remain open at a neutral pH, which improved the GABA productivity by 16.8% with 99.3 mol% conversion of 3 M L-Glu. Third, we enhanced the expression of soluble GadB by introducing the GroESL molecular chaperones, leading to 20.2% improvement in GABA productivity, with 307.40 g/L of GABA and a 61.48 g/L/h productivity obtained in one cycle. Finally, we inhibited the degradation of GABA by inactivation of gadA and gadB from the E. coli genome, which resulted in almost no GABA degradation after 40 h. After the cascade system modifications, the engineered recombinant E. coli strain achieved a 44.04 g/L/h productivity with a 99.6 mol% conversion of 3 M L-Glu in a 5-L bioreactor, about twofold increase in productivity compared to the starting strain. This increase represents the highest GABA productivity by whole-cell bioconversion using L-Glu as a substrate in one cycle observed to date, even better than the productivity obtained from the three successive conversion cycles.

Background Asthma is characterized by chronic airway inflammation, leading to structura1 changes in the airway, collectively termed airway remodeling. Airway remodeling is thought to contribute to airway hyper responsiveness and irreversible airflow limitation. The combination of Herba Epimedii (HE) and Fructus Ligustri Lucidi (FLL) decoction and the systemic administration of glucocorticoids (GC) had a synergistic inhibitory action on airway inflammation in the asthmatic model rats. However, the effects of the combination on airway remodeling have not been studied and compared. In the present study, we investigated the effects of the co-administration of combined extracts of HE and FLL with inhaled GC (budesonide) on airway remodeling in the rat asthmatic model induced by ovalbumin (OVA). Methods Male Sprague-Dawley rats were sensitized to intraperitoneal OVA followed by repetitive OVA challenge for 7 weeks. Treatments included extracts of HE and FLL (Extracts for short, 100 mg/kg by gastric perfusion), budesonide (1 mg budesonide suspension in 50 ml sterile physiological saline, 3 rats in an ultrasonic nebulizer by nebulized inhabation with a flow of 1.6 ml/min for 30 min), and co-administration of extracts of HE and FLL with budesonide (Co-administration for short) for 4 weeks. Lung histomorphometry and bronchoalveolar lavage fluid (BALF) cell count were assessed 24 h after the final OVA challenge. Levels of interleukin (IL)-4, IL-5 and IgE were measured by ELISA. Expressions of Collagen I and Collagen III were tested by immunohistology. Expressions of transforming growth factor (TGF) -β1, TGF-β2 and Smads mRNA were measured by quantitative real-time PCR. Results Extracts, budesonide and Co-administration significantly reduced allergen-induced increases in the serum levels of IL-4, IL-5 and IgE, the number of eosinophils in BALF, goblet cell hyperplasia, Collagen III integral optical density (IOD) and the mRNA expression of TGF-β2 and Smad2. Extracts and Co-administration could depress the IOD level of Collagen I and the positive area of Collagen I and Collagen III. Budesonide and Co-administration significantly alleviated the thickening of airway wall. Only Co-administration significantly decreased collagen deposition according to the morphometry of Masson’s-stained lung sections, the thickening of airway smooth muscle layer, the number of lymphocytes in BALF and the mRNA expression of TGF-β1 and Smad3, and this was associated with a significant increase in levels of Smad7 mRNA. Conclusions The findings suggested that the combination of budesonide and the herbal extracts had a better synergistic effect on airway remodeling in OVA-reduced asthma rats than the single use of budesonide.

Tang-Luo-Ning (TLN) has a definite effect in the clinical treatment of diabetic peripheral neuropathy (DPN). Schwann cells (SCs) apoptosis induced by endoplasmic reticulum stress (ER stress) is one of the main pathogeneses of DPN. This study investigates whether TLN can inhibit SCs apoptosis by inhibiting ER stress-induced apoptosis. Our previous researches have demonstrated that TLN could increase the expression of ER stress marker protein GRP78 and inhibited the expression of apoptosis marker protein CHOP in ER stress. In this study, the results showed that TLN attenuated apoptosis by decreasing Ca2+ level in SCs and maintaining ER morphology. TLN could decrease downstream proteins of CHOP including GADD34 and Ero1α, while it increased P-eIF2α and decreased the upstream proteins of CHOP including P-IRE1α/IRE1α and XBP-1, thereby reducing ER stress-induced apoptosis.

This study aimed to investigate the possible molecular mechanisms of active ingredients of Epimedii Folium (EF) and Ligustri Lucidi Fructus (LLF) combined with Budesonide (Bun) in asthmatic rats. Rats were divided into 5 groups, including normal group, asthma model group, Bun group, group of active ingredients of EL and LLF (EL), and group of coadministration of Bun with EL (Bun&EL). The asthmatic model was prepared by ovalbumin sensitizing and challenging. Lymphocyte apoptosis, GR protein and binding, and the protein and mRNA of GRα, GRβ, and HSP90 were tested. The results showed that Bun&EL ① markedly increased lymphocyte apoptosis, GR and HSP90 protein, and GR binding in BALF and ② enhanced the expressions of GRα and HSP90 and the ratio of GRα to GRβ or to HSP90 both in protein and in mRNA levels in lung, ③ while decrease occurred in GRβ mRNA and the mRNA ratio of GRβ to HSP90 compared with asthma or Bun group. Moreover, there was a significant correlation between GRα and GRβ in protein level, or between GRα and HSP90 both in protein and in mRNA levels. EL may effectively enhance the sensitivity of asthmatic rats to Bun via balancing GR/HSP90. And these findings will be beneficial for the treatment of asthma in the future.

Prolonged hyperglycemia-induced oxidative stress and endoplasmic reticulum stress have been demonstrated to play a key role in progression of diabetic peripheral neuropathy (DPN). PERK/ Nrf2 pathway plays a predominant role in oxidative and endoplasmic reticulum (ER) stress which is associated with cell survival. This study examined the modulation of the PERK/Nrf2 pathway and apoptosis by a traditional Chinese medicine Tangluoning (TLN) in streptozotocin-induced DPN rat models and the effects of serum TLN on the PERK/Nrf2 pathway, apoptosis, intracellular reactive oxygen species and mitochondrial membrane potential in Schwann cells cultured in 150 mM glucose. It is found that TLN attenuated oxidative and ER stress and apoptosis through the PERK/Nrf2 pathway by upregulating p-PERK, Nrf2/ARE pathways and downregulating the CHOP-related apoptosis pathways in the experimental DPN models both in vivo and in vitro.

Hepatocellular carcinoma with bile duct tumor thrombus (BDTT) is a malignant disease. The most commonly used diagnosis methods for BDTT are MRCP/ERCP, ultrasonic diagnosis or CT scan. However, BDTT is often misdiagnosed as other bile duct diseases, such as extrahepatic cholangiocarcinoma (EHCC), choledochal cyst (Cyst) and common bile duct stone (Stone). Diagnostic methods, which are more accurate and less destructive, are urgently needed. In this paper, we analyzed the small molecule metabolites in the serum of BDTT, Stone, Cyst and EHCC patients and normal people using untargeted GC-MS, and identified 21 metabolites that show different levels among different samples. Using targeted UHPLC-QQQ-MS analysis, we found that several metabolites are significantly changed. ROC curve analysis revealed two metabolites, L-citrulline and D-aspartic acid, as potential biomarkers that can distinguish BDTT from other bile duct diseases.

Abbreviation of paced QRS duration has been taken as electrical resynchronization imposed by cardiac resynchronization therapy (CRT). However, little is known about alteration in native QRS duration and its correlation with therapeutic response as well as anatomical remodeling post-CRT.Data of 74 consecutive patients with complete ECG records were reviewed. Response was defined as absolute improvement in LVEF by ≥10% from baseline. Changes in native QRS duration (native ΔQRS) were analyzed to CRT response and to changes in echocardiography.Over median follow-up of 13 months, 47 patients had response to CRT and 30 subjects had abbreviation in native QRS duration. Native ΔQRS correlated positively with QRS duration pre- and post-CRT as well as with changes in echocardiography. Reversal of electrical remodeling as assessed by native QRS narrowing accompanied with greater improvements in LVEF (20% ± 11% vs 10% ± 10%, p = 0.000) and LVEDD (14 ± 11 mm vs. 4 ± 10 mm, p = 0.000). Multivariate analysis indicated that native ΔQRS was the lone independent factor of ECG in association to response to CRT (OR1.049, 95%CI 1.015-1.085, p = 0.004): 83.3% of patients with native QRS reduction were responders. Among the non-responders, 18.5% had native QRS narrowing at follow-ups.Native QRS narrowing associated with beneficial response and greater improvements in echocardiography. Abbreviation in native QRS duration could reflect electrical reversal imposed by CRT.

Background Fragmented QRS (fQRS) marks inhomogeneous activation and asynchronous cardiac contraction. It has been proved that cardiac resynchronization therapy (CRT) could reverse geometrical remodeling as well as correct electrical dyssynchrony. We aimed to investigate whether fQRS changed corresponding to the therapeutic response to CRT. Methods Patients who underwent de novo CRT implantation previously and had ≥1 follow-up between August 2012 and September 2013 in our hospital were investigated. Intrinsic electrocardiogram was recorded and fQRS in any lead was calculated. Response to CRT was defined as absolute improvement in left ventricular ejection fraction by ≥10% or by improvement >1 New York Heart Association class and without heart failure hospitalization. Results A total of 75 patients (48 male, mean ages, 61 ± 9 years) were included in this study. At a median follow-up of 13 months, 57 patients had response to CRT. Responders had narrowed QRS (from 167 ± 23 ms to 158 ± 19 ms, P = 0.003) and reduced fQRS post-CRT. Nonresponders had QRS prolonging (from 151 ± 26 ms to 168 ± 16 ms, P = 0.033) and increase in fQRS. Eleven of 12 patients with reduced fQRS were responders and 8 of 12 with increased fQRS were nonresponders. Both changes in QRS and fQRS correlated strongly with CRT response (r = 0.389, P = 0.001 and r = 0.403, P = 0.000, respectively). Reduction of fQRS in ≥1 leads had high specificity (95%) in association to responders, though in low sensitivity (19%). Conclusions The changes in fQRS associated with therapeutic response to CRT. Regression of fQRS could be a maker of electrical reverse remodeling following CRT.

Subclinical thyroid dysfunction may be a risk factor for mortality in patients with heart failure and may be associated with dilated cardiomyopathy (DCM). This was a cohort study to examine the possible association between subclinical thyroid dysfunction and all-cause mortality in DCM patients, because the current evidence on this association remains elusive.A total of 963 DCM patients were evaluated for thyroid function. Of these patients, 7.1% (n = 68) had subclinical hyperthyroidism (defined as serum thyroid-stimulating hormone [TSH]0.35 μIU/mL), 84.7% (n = 816) had euthyroidism (TSH 0.35-5.5 μIU/mL), and 8.2% (n = 79) had subclinical hypothyroidism (TSH5.5 μIU/mL). There was a significant difference in all-cause mortality rates between patients with euthyroidism and patients with subclinical hyper- and hypothyroidism (21%, 38.2%, and 26.6%, respectively; log-rank χ(2) = 13.104; P = .001) with mean follow-up of 3.5 years. After adjustment for other confounding factors at baseline, QRS duration, N-terminal pro-B-type natriuretic peptide, New York Heart Association functional class, left atrial diameter, and subclinical hyperthyroidism (hazard ratio 1.793, 95% CI 1.010-3.183; P = .046) emerged as significant predictors of all-cause mortality.DCM patients with subclinical hyper- and hypothyroidism had higher all-cause mortality rates. However, only subclinical hyperthyroidism, not subclinical hypothyroidism, was an independent predictor for increased risk of all-cause mortality.

BACKGROUND The effect of adiposity on response to cardiac resynchronization therapy (CRT) and long-term outcome in patients undergoing CRT has not been previously reported. This study assessed the impact of baseline body mass index (BMI) on cardiac reverse remodeling and prognosis following CRT. METHODS AND RESULTS: A total of 247 CRT patients were included and divided into 4 groups according to baseline BMI. During 6-month follow-up, overweight and obese patients (BMI, 24-28 kg/m(2), ≥28 kg/m(2), respectively) were inclined to have better clinical and echocardiographic improvements (P

A novel esterase gene selected from metagenomic sequences of deep‐sea hydrothermal vents was successfully expressed in Escherichia coli. The recombinant protein (est‐OKK), which belongs to the lipolytic enzyme family V, exhibited high activity toward pNP‐esters with short acyl chains and especially p‐nitrophenyl butyrate. Site‐mutagenesis results confirmed that est‐OKK contains the nonclassical catalytic tetrad predicted by alignment and computational modeling. The est‐OKK protein is a moderately thermophilic enzyme that is relatively thermostable, and highly salt‐tolerant, which remained stable in 3 mol/L NaCl for 6 hr. The est‐OKK protein showed the considerable alkalistability, displayed optimal activity at pH 9.0 and maintained approximately 70% of its residual activity after incubation at pH 10 for 4 hr. Furthermore, the est‐OKK activity was strongly resistant to a variety of metal ions such as Co2+, Zn2+, Fe2+, Na+, and K+; nonionic detergents such as Tween‐20, Tween‐80; and organic solvents such as acetone and isopropanol. Taken together, the novel esterase with unique characteristics may give us a new insight into the family V of lipolytic enzymes, and could be a highly valuable candidate for biotechnological applications such as organic synthesis reactions or food and pharmaceutical industries.

Background The decoction combination of Herba Epimedii and Fructus Ligustri Lucidi has been used to treat osteoporosis for almost 50 years by practitioners of traditional Chinese medicine. However, it is unclear what specific effects this combination of herbs has on the skeleton. The aim of this study was to assess the effects of the combined extracts from Herba Epimedii and Fructus Ligustri Lucidi on the bone turnover and bone mineral content in a rat model of osteoporosis induced by retinoic acid. Methods Fifty male Wistar rats were randomly assigned to the normal control group, osteoporosis model group, or treatment groups in which osteoporosis was induced and then the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi were administered at 50, 100, or 200 mg/kg/day for 3 weeks via oral gavage. The rat osteoporosis model was induced by intragastric administration of 70 mg/kg/day of retinoic acid for 2 weeks. Bone turnover markers, bone biomechanical properties, and the calcium and phosphorus content of the right tibia and serum were measured. Results The retinoic acid administration decreased the bone mass and the contents of calcium and phosphorus in the bone mineral, weakened the biomechanical properties, and increased bone turnover by stimulating bone resorption and collagen metabolism. Treatment with the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi significantly mitigated the effects of osteoporosis on the rats by decreasing bone metabolism, improving the bone mineral content, and increasing the biomechanical properties. Conclusions The results of this study highlight the anti-osteoporosis effects of the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi. These findings may contribute to the development of natural anti-osteoporosis herbal medicines.

Tang Luo Ning recipe (TLN), a traditional Chinese herbal medicine based on Huangqi Guizhi Wuwu decoction, has been used clinically to treat diabetic peripheral neuropathy in China. However, the effect of TLN on diabetic peripheral neuropathy is unclear. The objective of this study was to determine the main components in TLN and to investigate the effects of TLN on oxidative stress in diabetic peripheral neuropathy rats.The effect of TLN on oxidative stress was investigated in streptozocin (STZ)-induced diabetic rats. Fasting blood glucose, body weight, thermal perception threshold test and motor and sensory nerve conduction velocity of sciatic nerve were measured. Sciatic nerve morphology was observed by Haematoxylin and eosin staining and under transmission electron microscope. T-AOC was measured by colorimetric assay. ROS were measured using enzyme-linked immunosorbent assay. Nrf2 and γGCS protein levels were measured by Western blot analysis. The expression of Bcl2, Bax and Cyto C were examined by immunohistochemistry.TLN markedly improved the neurological function including thermal perception threshold and nerve conduction velocity of DPN rats. Haematoxylin and eosin (HE) and transmission electron microscopy (TEM) staining results showed that TLN attenuated axon atrophy and demyelination in DPN rats. Moreover, TAOC were increased, whereas ROS content was decreased after treatment with TLN in rats with DPN. Furthermore, TLN increased protein levels of Nrf2, γGCS and Bcl2, and decreased Bax and Cyto C expression.TLN improved neurological function to prevent diabetic peripheral neuropathy by attenuating oxidative stress through Nrf2 and Bcl2 activation.

Background Tang Bi Kang (TBK) is a traditional Chinese medicine granule. It has been shown to have effects on nerve conduction velocity deficits, blood-related factors and oxidative stress. This study was undertaken to evaluate proposed antioxidative and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy (DPN). Methods DPN was induced in male Wistar rats by intraperitoneal administration of streptozocin (STZ) (60 mg/kg.b.w) for 8 weeks. Fasting blood glucose (FBG) levels were measured in the blood obtained by clipping the tails of the rats. Tail-flick tests were conducted with a tail-flick analgesic meter. Motor and sensory nerve conduction velocities (MNCV and SNCV) of sciatic nerve were measured directly at two sites using a Functional Experiment System. Oxidative stress makers such as malondialdehyde (MDA), superoxide-dismutase (SOD) and glutathione peroxidase (GSH-Px), inflammatory cytokines such as interleukin (IL)-6, and tumour necrosis factor (TNF)-α were estimated. The statistical analysis of results was carried out using Student t-test and one-way analysis of variance (ANOVA), followed by least-significant difference post hoc with SPSS. Results The administration of TBK for 4 weeks in DPN rats resulted in a significant decrease in FBG levels compared to untreated DPN rats. There was a significant increase in MNCV and SNCV in the DPN rats compared to untreated DPN rats. Serum level of MDA was significantly reduced while the activities of SOD and GSH-pX were significantly increased in the TBK treated DPN rats. TBK prevented DPN-induced increase in the serum levels of IL-6 and TNF-α. Conclusion The results of this study demonstrate that the therapeutic effect of TBK on DPN rats may be associated with the antioxidative and anti-inflammatory responses.

The combination of Herba Epimedii and Fructus Ligustri Lucidi has been used to treat osteoporosis for almost 50 years by Professor Shizeng Li, a famous doctor of traditional Chinese medicine (TCM). However, it is unclear whether the combination of the effective constituents of the two herbs may have a protective influence on the skeleton. In the present study, we investigated the effects of the combination extracts of Herba Epimedii and Fructus Ligustri Lucidi on rat model of osteoporosis induced by retinoic acid by gavage. With administrations of the combination extracts of the two herbs (50, 100, and 200 mg/kg/day) via oral gavage for 3 weeks, bone mineral density (BMD), femur histomorphometry, some sex hormones, and sex hormone receptors were measured. Results showed that the combined extracts could increase BMD, affect bone histomorphometry, coordinate the sex hormones at the level of hypothalamus-pituitary-gonad axis, and increase the protein and mRNA expressions of sex hormone receptors. The findings suggested that the combination extracts of Herba Epimedii and Fructus Ligustri Lucidi might be beneficial as an alternative medicine for the prevention and treatment of osteoporosis.

BackgroundIntrahepatic recurrence is a significant problem for patients who have undergone a hepatic resection for hepatocellular carcinoma (HCC). The objective of the present study was to identify risk factors and evaluate the management of early and late recurrence of solitary HCC after curative resection.MethodsIncluded in this study were 816 patients with solitary HCC who underwent a curative partial hepatectomy. Intrahepatic recurrence in these patients was followed up retrospectively. Prognosis and therapy for the recurrence were investigated and analysed.ResultsEarly and late intrahepatic recurrence occurred in 423 patients and 199 patients, respectively. Multivariate analysis showed that a tumour diameter >5 cm, the absence of a tumour capsule and the presence of microvascular invasion were correlated with early recurrence, whereas cirrhosis and alphafetal protein >400 μg/l were independent risk factors contributing to late recurrence. The 5year survival of HCC patients with early recurrence was significantly lower than that of patients with late recurrence. Further curative treatment for intrahepatic recurrence offered a 5year overall survival of 56.0%, which was better than alternative management.ConclusionEarly and late recurrences of solitary HCC after curative resection are associated with different predictive factors. The time to recurrence and further curative treatment after recurrence were the best predictors of survival post recurrence.

The objective of this study was to provide the morphological details on small branches of the portal vein in transverse groove of hepatic hilum.According to the surgery significance, the small branches of portal vein in transverse groove of hepatic hilum were named as "Short hepatic portal veins (SHPVs)". SHPVs were minutely dissected in 30 adult cadaveric livers. The number, diameter, length, origin points, and entering liver sites of SHPVs were explored and measured.There were 181 SHPVs in 30 liver specimens, including 46% (83/181) from the left portal vein, 31% (56/181) from the bifurcation, and 23% (42/181) from the right portal vein. At the entering liver sites of SHPVs, 22% (40/181) supplied for segment IV, 9% (17/181) for segment V, 4% (7/181) for segment VI, 23% (41/181) for segment VII, and 42% (76/181) for segment I (caudate lobe). There were 6.0 ± 2.4 branches per liver specimen with range 3-12. The mean diameter of SHPVs was 2.25 ± 0.89 mm. The average length of SHPVs was 4.86 ± 2.12 mm.SHPVs widely existed in each liver specimen. The detailed anatomical study of SHPVs could be useful to avoid damaging the short portal branches during hepatic operations, such as isolated or combined caudate lobectomy.

Background Mucin-producing bile duct tumors (MPBTs) are unusual, and we present our experience with nine surgically proven cases. Methods Between November 2002 and November 2012, 9 patients with surgically proven MPBTs (including history of relevant hepatobiliary surgery in 6 patients) were encountered. Their clinical, imaging, and surgical findings were reviewed. Results The most common symptom is intermittent jaundice, which occurs in seven patients. The diagnostic specificity was 77.8% by preoperative Magnetic Resonance Cholangiopancreatography (MRCP). All the patients underwent ipsilateral hemihepatectomy or remnant hemihepatectomy, accompanied caudate lobectomy in one case and concomitant Roux-en-Y choledochojejunostomy in four cases. Postoperative course was uneventful. One patient, who had intra-abdominal recurrence 59 months after surgery, was received reoperation without recurrence at the last follow-up. The remaining eight patients were alive without disease recurrence. Conclusion Based on our follow up of 9 cases that were surgically treated for MPBTs, we conclude that ipsilateral hemihepatectomy is a safe surgical procedure with an observed recurrence risk of 11.1% and all long-term survival.

Both the B cell antigen receptor (BCR) signaling and Notch signaling pathway play important roles in marginal zone (MZ) B cell development; however, if and how these two signaling pathways engage in crosstalk with each other remain unclear. In the present study, IgH transgenic mice (TgV(H)3B4) were crossed with mice with Notch downstream transcription factor RBP-J floxed alleles (RBP-J(f/f)) and Mx-Cre transgene. Subsequently, MZ B cell development was analyzed in 3B4/Cre/RBP-J(f/f) mice that expressed the transgenic 3B4 IgH and exhibited a deficiency in Notch signaling in B cells upon poly (I:C) injection. We observed that MZ B cell numbers were severely reduced, but still detectable in 3B4/Cre/RBP-J(f/f) mice, in contrast to increased numbers of MZ B cells in TgV(H)3B4 mice and almost no MZ B cells in Cre/RBP-J(f/f) mice. The majority of the MZ B cells in the 3B4/Cre/RBP-J(f/f) mice had the same antigen specificity with that of 3B4 antibody, indicating that a particular BCR specificity might direct MZ B cell development in the absence of Notch signaling. The number of MZ B precursor (MZP) cells was reduced sharply in 3B4/Cre/RBP-J(f/f) mice, and the number of transitional stage 1 and transitional stage 2 cells did not change that much, indicating that the interaction between BCR and Notch signaling likely occurred during the T2-MZP stage. Based on the transgenic mouse model, our data indicate that MZ B cells with certain BCR specificity can develop in a Notch-RBP-J independent manner.