Acarbose enhances the efficacy of immunotherapy against solid tumours by modulating the gut microbiota.

The crucial role of gut microbiota in shaping immunotherapy outcomes has prompted investigations into potential modulators. Here we show that oral administration of acarbose significantly increases the anti-tumour response to anti-PD-1 therapy in female tumour-bearing mice. Acarbose modulates the gut microbiota composition and tryptophan metabolism, thereby contributing to changes in chemokine expression and increased T cell infiltration within tumours. We identify CD8+ T cells as pivotal components determining the efficacy of the combined therapy. Further experiments reveal that acarbose promotes CD8+ T cell recruitment through the CXCL10-CXCR3 pathway. Faecal microbiota transplantation and gut microbiota depletion assays indicate that the effects of acarbose are dependent on the gut microbiota. Specifically, acarbose enhances the efficacy of anti-PD-1 therapy via the tryptophan catabolite indoleacetate, which promotes CXCL10 expression and thus facilitates CD8+ T cell recruitment, sensitizing tumours to anti-PD-1 therapy. The bacterial species Bifidobacterium infantis, which is enriched by acarbose, also improves response to anti-PD-1 therapy. Together, our study endorses the potential combination of acarbose and anti-PD-1 for cancer immunotherapy.

Recombinant human adenovirus type 5 promotes anti-tumor immunity via inducing pyroptosis in tumor endothelial cells.

Recombinant human type 5 adenovirus (H101) is an oncolytic virus used to treat nasopharyngeal carcinoma. Owing to the deletion of the E1B-55kD and E3 regions, H101 is believed to selectively inhibit nasopharyngeal carcinoma. Whether H101 inhibits other type of tumors via different mechanisms remains unclear. In this study we investigated the effects of H101 on melanomas. We established B16F10 melanoma xenograft mouse model, and treated the mice with H101 (1 × 108 TCID50) via intratumoral injection for five consecutive days. We found that H101 treatment significantly inhibited B16F10 melanoma growth in the mice. H101 treatment significantly increased the infiltration of CD8+ T cells and reduced the proportion of M2-type macrophages. We demonstrated that H101 exhibited low cytotoxicity against B16F10 cells, but the endothelial cells were more sensitive to H101 treatment. H101 induced endothelial cell pyroptosis in a caspase-1/GSDMD-dependent manner. Furthermore, we showed that the combination of H101 with the immune checkpoint inhibitor PD-L1 antibody (10 mg/kg, i.p., every three days for three times) exerted synergic suppression on B16F10 tumor growth in the mice. This study demonstrates that, in addition to oncolysis, H101 inhibits melanoma growth by promoting anti-tumor immunity and inducing pyroptosis of vascular endothelial cells.

[Corrigendum] High glucose and high insulin conditions promote MCF­7 cell proliferation and invasion by upregulating IRS1 and activating the Ras/Raf/ERK pathway.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, in the wound­healing assays portrayed in Fig. 2A on p. 6692, in the 0 h row, the 'NG + LI' and 'HG + HI' panels contained overlapping data, such that they appeared to have been derived from the same original source. After having examined their original data, the authors have realized that this figure was inadvertently assembled incorrectly. The corrected version of Fig. 2. showing the correct data for the 'HG + HI' panel, is shown on the next page. Note that this error did not significantly affect the results or the conclusions reported in this paper, and all the authors agree with the publication of this Corrigendum. Furthermore, the authors apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 6690­6696, 2017; DOI: 10.3892/mmr.2017.7420].

An effective treatment and suspicious adverse reaction to Ibrutinib in a patient diagnosed with splenic B-cell lymphoma/leukaemia with prominent nucleoli: A first case report.

RATIONALE: Splenic B-cell lymphoma/leukemia with prominent nucleoli (SBLPN) is a new classification, which is so rare that it lacks clinical data. PATIENT CONCERNS: An increased proportion of prolymphocytes (84%) in the bone marrow smear. Whole exon sequence analysis revealed a TP53 mutation. DIAGNOSES: Combining the clinical features with laboratory test results led to a diagnosis of SBLPN which was made according to the 5th edition of the WHO classification of hematolymphoid tumors, although the patient was diagnosed with B-PLL when guided by the 4th edition of the WHO classification. INTERVENTIONS: The use of Ibrutinib as an effective treatment. OUTCOMES: The patient was in complete remission after 5 months of Ibrutinib and then died of sudden aortic dissection. LESSONS: Ibrutinib was an effective regimen for SBLPN. Aortic dissection might be considered as a suspicious adverse reaction to Ibrutinib.

Anlotinib plus Epirubicin Followed by Anlotinib Maintenance as First-line Treatment for Advanced Soft-tissue Sarcoma: An Open-label, Single-arm, Phase II Trial.

PURPOSE: The treatment outcome for locally advanced or metastatic soft-tissue sarcoma (STS) remains unsatisfactory. Anlotinib had demonstrated impressive activity in the subsequent-line treatment of STS. This study investigated the combination of anlotinib and epirubicin followed by anlotinib maintenance as first-line treatment for patients with advanced STS. PATIENTS AND METHODS: This prospective, open-label, single-arm, phase II trial was conducted in Zhongshan Hospital, Fudan University. Eligible patients were ages 18 years or older and had previously untreated, pathologically confirmed, unresectable locally advanced or metastatic STS. All patients received up to six cycles of anlotinib plus epirubicin followed by anlotinib maintenance until disease progression, unacceptable toxicity, or death. The primary endpoint was the progression-free survival (PFS) rate at 6 months. The study was registered on chictr.org (identifier ChiCTR1900024928). RESULTS: From June 2019 to August 2020, 30 patients were enrolled. By December 2021, the median PFS was 11.5 months [95% confidence interval (CI): 8.6-14.4 months], while the median overall survival was not reached (95% CI: NE-NE). The objective response rate was 13.33% and the disease control rate was 80.0%. The most common adverse events (AE) included anemia (43.3%), nausea/vomiting (40.0%), fatigue (36.7%), leukopenia (30.0%), and proteinuria (10.0%), which were mainly of grade 1 or 2. The most frequent grade 3 or 4 AEs were anemia (10.0%), febrile neutropenia (33.3%), hypothyroidism (3.3%), and leukopenia (3.3%). No treatment-related death occurred. CONCLUSIONS: The combination of anlotinib and epirubicin followed by anlotinib maintenance demonstrated promising efficacy with a favorable safety profile.

Essential thrombocythemia with non-ST-segment elevation myocardial infarction as the first manifestation: A case report.

BACKGROUND: We report a case of essential thrombocythemia (ET) in a 44-year-old male who exhibited non-ST-segment-elevation myocardial infarction (NSTEMI) as the first manifestation without known cardiovascular risk factors (CVRFs). For the first time, we reported a left main trifurcation lesion in NSTEMI caused by ET, including continuous stenosis lesions from the left main to the ostial left anterior descending (LAD) artery and an obvious thrombotic lesion in the ostial and proximal left circumflex (LCX) artery. There was 60% diffuse stenosis in the left main (LM) that extended to the ostial LAD, thrombosis of the ostial LAD and proximal LCX, and 90% stenosis in the proximal LCX. During the operation, thrombus aspiration was performed, but no obvious thrombus was aspirated. Performing the kissing balloon technique (KBT) in the LCX and LM unexpectedly increased the narrowness of the LAD. Then, the single-stent crossover technique, final kissing balloon technique and proximal optimization technique (POT) were performed. On the second day after percutaneous coronary intervention (PCI), the number of platelets (PLTs) still increased significantly to as high as 696 × 109/L. The bone marrow biopsy done later, together with JAK2 (exon 14) V617F mutation, confirms the diagnosis of ET. Hydroxyurea was administered to inhibit bone marrow proliferation to control the number of PLTs. CASE SUMMARY: A 44-year-old male patient went to a local hospital for treatment for intermittent chest pain occurring over 8 h. The examination at the local hospital revealed elevated cTnI and significantly elevated platelet. Then, he was diagnosed with acute myocardial infarction and transferred to our hospital for emergency interventional treatment by ambulance. During the operation, thrombus aspiration, the single-stent crossover technique, final kissing balloon technique and POT were performed. Dual antiplatelet therapy comprising aspirin and ticagrelor was used after PCI. Evidence of mutated JAK2 V617F and bone marrow biopsy shown the onset of ET. Together with JAK2 (exon 14) V617F mutation, ET was diagnosed according to the World Health Organization (WHO) diagnostic criteria, and the patient was placed on hydroxyurea. During the one-year postoperative period, repeated examinations showed a slight increase in PLTs, but the patient no longer had chest tightness, chest pain or bleeding or developed new thromboembolisms. CONCLUSION: Routine physical examinations and screenings are conducive to the early detection of ET, and the risk for thrombosis should be assessed. Then, active antiplatelet therapy and myelosuppression therapy should be used for high-risk ET patients.

Recombinant Rice Quiescin Sulfhydryl Oxidase Strengthens the Gluten Structure through Thiol/Disulfide Exchange and Hydrogen Peroxide Oxidation.

Recombinant rice quiescin sulfhydryl oxidase (rQSOX) has the potential to improve the flour processing quality, but the mechanisms remain unclear. The effects of rQSOX on bread quality, dough rheology, and gluten structure and composition, with glucose oxidase as a positive control, were investigated. rQSOX addition could improve the dough processing quality, as proved by enhanced viscoelastic properties of dough as well as a softer crumb, higher specific volume, and lower moisture loss of bread. These beneficial effects were attributed to gluten protein polymerization and gluten network strengthening, evidenced by the improved concentration of SDS-insoluble gluten and formation of large gluten aggregates and the increased α-helix and ß-turn conformation. Furthermore, decreased free sulfhydryl and increased dityrosine in gluten as well as improved H2O2 content in dough suggested that the rQSOX dough strengthening mechanism was mainly based on the formation of disulfide bonds and dityrosine cross-links in gluten by both thiol/disulfide direct exchange and hydrogen peroxide indirect oxidation pathways.

The Specifically Androgen-Regulated Gene (SARG) Promotes Papillary Thyroid Carcinoma (PTC) Lymphatic Metastasis Through Vascular Endothelial Growth Factor C (VEGF-C) and VEGF Receptor 3 (VEGFR-3) Axis.

The papillary thyroid carcinoma (PTC) metastasizes through lymphatic spread, but the follicular thyroid cancer (FTC) metastasis occurs by following hematogenous spread. To date, the molecular mechanism underlying different metastatic routes between PTC and FTC is still unclear. Here, we showed that specifically androgen-regulated gene (SARG) was significantly up-regulated in PTC, while obviously down-regulated in FTC through analyzing the Gene Expression Omnibus (GEO) database. Immunohistochemistry assay verified that the PTC lymph node metastasis was associated with higher levels of SARG protein in clinical PTC patient samples. SARG-knockdown decreased TPC-1 and CGTH-W3 cells viability and migration significantly. On the contrary, SARG-overexpressed PTC cells possessed more aggressive migratory ability and viability. In vivo, SARG overexpression dramatically promoted popliteal lymph node metastasis of xenografts from TPC-1 cells mouse footpad transplanting. Mechanistically, SARG overexpression and knockdown significantly increased and decreased the expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor 3 (VEGFR-3), respectively, thereby facilitating or inhibiting the tube formation in HUVECs. The tube formation experiment showed that SARG overexpression and knockdown promoted or inhibited the number of tube formations in HUVEC cells, respectively. Taken together, we showed for the first time the differential expression profile of SARG between PTC and FTC, and SARG promotes PTC lymphatic metastasis via VEGF-C/VEGFR-3 signal. It indicates that SARG may represent a target for clinical intervention in lymphatic metastasis of PTC.

CsCCD2 Access Tunnel Design for a Broader Substrate Profile in Crocetin Production.

Crocetin, a high-value apocarotenoid in saffron, is widely applied to the fields of food and medicine. However, the existing method of obtaining crocetin through large-scale cultivation is far from meeting the market demand. Microbial synthesis of crocetin is a potential alternative to traditional resources, and it is found that carotenoid cleavage dioxygenase (CCD) is the critical enzyme to synthesize crocetin. So, in this study, we used "hybrid-tunnel" engineering to obtain variants of Crocus sativus-derived CsCCD2, essential for zeaxanthin conversion into crocetin, with a broader substrate specificity and higher catalytic efficiency. Variants including S323A, with a lower charge bias and a larger tunnel size than the wild-type, showed a 5-fold higher crocetin titer in yeast-based fermentations. S323A could also convert the ß-carotene substrate to crocetin dialdehyde and exhibited a 12.83-fold greater catalytic efficiency (kcat/Km) toward zeaxanthin than the wild-type in vitro. This strategy enabled the production of 107 mg/L crocetin in 5 L fed-batch fermentation, higher than that previously reported. Our findings demonstrate that engineering access tunnels to expand the substrate profile by in silico protein design represents a viable strategy to refine the catalytic properties of enzymes across a range of applications.

Robust W/O/W Emulsion Stabilized by Genipin-Cross-Linked Sugar Beet Pectin-Bovine Serum Albumin Nanoparticles: Co-encapsulation of Betanin and Curcumin.

Betanin and curcumin hold promise as natural colorants and antioxidants for food purposes due to their anti-hypertensive, anti-inflammation, and anti-tumor effects. However, the thermal stability and bioavailability of betanin and curcumin still need improvement. Here, we fabricated sugar beet pectin-bovine serum albumin nanoparticles (SBNPs) with a mean particle size of 180 ± 5.2 nm through a genipin cross-linking strategy to stabilize a type of Pickering water-in-oil-in-water (W/O/W) emulsion and co-encapsulated betanin and curcumin. First, the W1/O emulsion was homogenized with gelatin (the gelling agent) in the water phase and polyglycerol polyricinoleate (a lipophilic surfactant) in the oil phase. Later, W1/O was homogenized with another water phase containing SBNPs. The microstructure of the emulsion was regulated by the particle concentration (c) and W1/O volume fraction (Φ), especially the gel-like high internal phase emulsions were formed at the Φ up to 70%. In this case, betanin was encapsulated in the internal water phase (encapsulation efficiency = 65.3%), whereas curcumin was in the medium-chain triglyceride (encapsulation efficiency = 84.1%). Meanwhile, the shelf stability of betanin and curcumin was improved. Furthermore, the stability of bioactive compounds was potentiated by an emulsion gel in simulated gastrointestinal digestion, resulting in higher bioaccessibility. The aforementioned results suggest that SBNP-stabilized Pickering W/O/W emulsions could be a potential alternative to co-encapsulate betanin and curcumin with enhancement of shelf stability and bioaccessibility.

Relevance on the diagnosis of malignant lymphoma of the salivary gland.

Malignant lymphoma originates from the lymphohematopoietic system. It can occur in any lymphoid tissue. Malignant lymphoma of the salivary gland is rare, but its incidence has increased in recent years. Its clinical- presentations are non-specific, and it is often manifested as a painless mass in a salivary gland, which can be accompanied by multiple swollen cervical lymph nodes. Confirmation of the diagnosis before an invasive procedure is difficult. Clinically, malignant lymphoma of the salivary gland tends to be misdiagnosed, leading to an inappropriate treatment plan and the ultimate delay in the optimal treatment of the disease. This article reviews the pathogenesis, clinical features, imaging findings, diagnosis, treatment and prognosis of malignant lymphoma of the salivary gland.

Two sequential surgeries in infant with multiple floor of the mouth dermoid cysts: A case report.

BACKGROUND: Multiple intraoral dermoid cysts of large magnitude generally appear in the second or third decade of life. They are rare in infants and are usually solitary. In this case, a large mass was identified in utero during prenatal exams. CASE SUMMARY: We introduce a rare case on multiple dermoid cysts in the floor of the mouth of an infant who underwent two surgeries for this. Preoperative magnetic resonance imaging confirmed a large well-circumscribed cystic lesion that originated at the former midline region in the floor of the mouth in which a suspicious lesion of minute size was likely compressed by the bulkier mass and overlooked. Therefore, the infant underwent two surgeries by an intraoral approach within 9 mo. At 5 mo after the second operation, a routine follow-up ultrasound showed evidence of an additional cyst. No further surgery was planned because the tumor had no immediate effect. CONCLUSION: This report demonstrates the importance of carefully analyzing preoperative imaging to avoid multiple operations for a seemingly isolated oral cyst.

Incidence, Prognostic Factors and Survival Outcome in Patients With Primary Hepatic Lymphoma.

Aim: The objective of our study was to investigate the epidemiologic characteristics, prognostic factors and survival in patients with primary hepatic lymphoma (PHL). Methods: PHL patients diagnosed between 1983 and 2015 were identified from the SEER database. The temporal trend in PHL incidence was assessed using joinpoint regression software. Overall survival(OS) and disease-specific survival (DSS) was evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analysis was performed to identify the independent prognostic factors for OS and DSS. Nomograms to predict survival possibilities were constructed based on the identified independent prognostic factors. Results: A total of 1,182 patients were identified with PHL. The mean age was 61.7 ± 17.1 years with a male to female of 1.6:1. Diffuse large B-cell lymphoma (59.8%) was the most common histological subtype. The incidence of PHL steadily increasing by an annual percentage change (APC) of 2.6% (95% CI 2.0-3.2, P < 0.05). The 1-, 5-, and 10-year OS rates were 50.85, 39.6, and 30.4%, respectively, and the corresponding DSS rates were 55.3, 47.9, and 43.3%, respectively. Multivariate Cox regression analysis revealed that age, sex, race, marital status, histological subtype, surgery, and chemotherapy were independent prognostic factors for survival. Nomograms specifically for DLBCL were constructed to predict 1-, 5-, and 10-year OS and DSS possibility, respectively. The concordance index (C-index) and calibration plots showed the established nomograms had robust and accurate performance. Conclusion: PHL were rare but the incidence has been steadily increasing over the past four decades. Survival has improved in recent years. Surgery or chemotherapy could provide better OS and DSS. The established nomograms specifically for DLBCL were robust and accurate in predicting 1-, 5-, and 10-year OS and DSS.

SmCOI1 affects anther dehiscence in a male-sterile Solanum melongena line.

Anther indehiscence is an important form of functional male sterility that can facilitate the production of hybrid seed; however, the molecular mechanisms of anther indehiscence-based male sterility have not been thoroughly explored in eggplant (Solanum melongena L.). Here, we used two-dimensional gel electrophoresis to compare the protein profiles in the anthers of normally developing (F142) and anther indehiscent (S16) S. melongena plants. Four differentially expressed proteins were identified using matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry. Of these proteins, the transcript accumulation of the eggplant CORONATINE INSENSITIVE1 (SmCOI1) was significantly downregulated in S16 relative to F142. Phylogenetic analysis showed that SmCOI1 has high amino acid sequence similarity and clustered into the same subgroup as its homologs in other members of the Solanaceae. Subcellular localization analysis showed that SmCOI1 localized to the nucleus. Moreover, reverse-transcription quantitative PCR revealed that the jasmonic acid pathway genes SmJAZ1 and SmOPR3 are upregulated in F142 relative to S16. Protein-protein interaction studies identified a direct interaction between SmCOI1 and SmOPR3, but SmCOI1 failed to interact with SmJAZ1. These findings shed light on the regulatory mechanisms of anther dehiscence in eggplant.

Polycystic liver disease: Classification, diagnosis, treatment process, and clinical management.

Polycystic liver disease (PLD) is a rare hereditary disease that independently exists in isolated PLD, or as an accompanying symptom of autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease with complicated mechanisms. PLD currently lacks a unified diagnostic standard. The diagnosis of PLD is usually made when the number of hepatic cysts is more than 20. Gigot classification and Schnelldorfer classification are now commonly used to define severity in PLD. Most PLD patients have no clinical symptoms, and minority with severe complications need treatments. Somatostatin analogues, mammalian target of rapamycin inhibitor, ursodeoxycholic acid and vasopressin-2 receptor antagonist are the potentially effective medical therapies, while cyst aspiration and sclerosis, transcatheter arterial embolization, fenestration, hepatic resection and liver transplantation are the options of invasion therapies. However, the effectiveness of these therapies except liver transplantation are still uncertain. Furthermore, there is no unified strategy to treat PLD between medical centers at present. In order to better understand recent study progresses on PLD for clinical practice and obtain potential directions for future researches, this review mainly focuses on the recent progress in PLD classification, clinical manifestation, diagnosis and treatment. For information, we also provided medical treatment processes of PLD in our medical center.

Analysis of nicotine-induced metabolic changes in Blakeslea trispora by GC-MS.

Blakeslea trispora is a natural source of carotenoids, including ß-carotene and lycopene, which have industrial applications. Therefore, classical selective breeding techniques have been applied to generate strains with increased productivity, and microencapsulated ß-carotene preparation has been used in food industry (Li et al., 2019). In B. trispora, lycopene is synthesized via the mevalonate pathway (Venkateshwaran et al., 2015). Lycopene cyclase, which is one of the key enzymes in this pathway, is a bifunctional enzyme that can catalyze the cyclization of lycopene to produce ß-carotene and exhibit phytoene synthase activity (He et al., 2017).

Efficacy and safety of anlotinib, a multikinase angiogenesis inhibitor, in combination with epirubicin in preclinical models of soft tissue sarcoma.

BACKGROUND: Anlotinib is a novel, orally administered, multitarget receptor tyrosine kinase inhibitor. It functions by inhibiting tumor angiogenesis and proliferative signaling pathways. In this study, we aimed to investigate the efficacy and safety of anlotinib plus epirubicin in a sarcoma patient-derived xenografts (PDX) model. METHODS: We firstly established a PDX model using fresh tumor tissues that were surgically removed from a patient diagnosed with malignant fibrous histiocytoma. Thirty-six PDX models were divided into six groups and treated with anlotinib alone (low-dose, 1.5 or high-dose, 3.0 mg/kg/day, oral gavage), or with anlotinib plus epirubicin (3.0 mg/kg/once weekly, i.p.) when the tumors grew to 150-200 mm3 . After 5 weeks of treatment, the mice were sacrificed, and the tumors were measured by weight and processed for IHC and H&E staining. IHC staining was performed to detect CD31, EGFR, MVD, and Ki-67 on paraffin sections. H&E stainings were performed to examine the microcosmic changes that occurred in the tumor tissues and myocardium, respectively. RESULTS: After 5 weeks, treatment with anlotinib or epirubicin alone significantly inhibited tumor growth in the sarcoma PDX model compared with the vehicle control. Tumor volume in the high-dose anlotinib group was significantly smaller than the low-dose anlotinib group (P < .001). Combined high-dose anlotinib and epirubicin treatment resulted in the most pronounced tumor inhibition. In the groups treated with the anlotinib-containing regimen, the expression levels of CD31, EGFR, MVD, and Ki-67 were significantly low. The weight in each group had no statistical differences; the same applied to the hepatic function, cardiac function, and toxicity. CONCLUSIONS: High-dose anlotinib combined with epirubicin was an effective and safe therapy for STS.

[The immune microenvironment in maternal-fetal interface contributes to the parturition and preterm labor].

The maintenance of human pregnancy and the initiation of parturition are closely related with the dynamic balance of the maternal-fetal immune microenvironment. Implantation of the blastocyst into the maternal decidua is the first step in pregnancy establishment, which is favored by the abundant blood flow and the immunotolerant microenvironment maintained by the balance of immune cells. The parturition resembles an inflammatory response that includes secretion of cytokines by resident and infiltrating immune cells into reproductive tissues and the maternal-fetal interface, which promotes the delivery of fetus from maternal organism. Therefore, the immune microenvironment in maternal-fetal interface regulates the critical steps of pregnancy and parturition. When the maternal-fetal immune microenvironment is imbalanced or impaired, miscarriage or preterm labor would happen. This article reviews the roles and mechanisms of several important immune cells in the maternal-fetal interface during the parturition and preterm labor.

Survival and analysis of prognostic factors for hepatoblastoma: based on SEER database.

BACKGROUND: The goal of this study is to assess the newest survival of hepatoblastoma (HB) and the risk factors which impacted on survival by using the Surveillance, Epidemiology and End Results (SEER) database, also calculate the incidence of HB in recent years. METHODS: We calculate age-adjusted incidence of HB by using SEER 21 registries. Age, sex, race, tumor size, macrovascular involvement, multifocal tumor, distant metastasis, the way of treatment, and the survival were collected for survival and analysis of prognostic factors in SEER 18 registries. Survival curves, according to different factors, were obtained by Kaplan-Meier estimates. Multivariable Cox regression models were also built. RESULTS: The overall age-adjusted incidence of HB was 0.19 patients per 100,000 children with a statistically significant increase per year. Overall survival (OS) at 1-, 3- and 5-year for all patients were 89.3%, 84.6%, and 81.9%, respectively. Multivariate analysis showed tumor size >5 cm [hazard ratio (HR), 8.271; 95% confidence interval (CI), 1.134-60.310], multiple tumors (HR, 2.578; 95% CI, 1.424-4.668) and no-surgery treatment (HR, 7.520; 95% CI, 4.121-13.724) were independent indicators of poor prognosis. Only the age ≥2-year-old (HR, 3.240; 95% CI, 1.433-7.326) and multiple tumors (HR, 2.395; 95% CI, 1.057-5.430) were the risk factors for the surgical treatment group. CONCLUSIONS: The survival of patients with HB has been greatly improved in the recent years, and at the same time, due to the application of better chemotherapy, we should re-evaluate the traditional risk indicators of prognosis in order to better apply to the clinical.

Comparative Metabolic Responses Induced by Pyridine and Imidazole in Blakeslea trispora.

Lycopene cyclase needs to be inhibited by the blockers like pyridine or imidazole in the lycopene accumulation of Blakeslea trispora. This work investigated how pyridine and imidazole impacted the basal metabolism of B. trispora, the results helped us understand how they could affect the lycopene production and application, and see the metabolic risks from different inhibitors. In this study, the highest yield of lycopene with pyridine was obtained at 176 mg/L without amino acids supplement, and got more lycopene at 237 mg/L adding tyrosine, lysine, proline all together as 0.01 mol/L each in fermented broth. GC-MS and Principal Component Analysis (PCA) were used to find that amino acids, fatty acids, organic acids including phosphoric acid, carbon source and imidazole derivatives played the most important roles in lycopene fermentation with imidazole, differently, fatty acids, carbon source, and pyridine derivatives were more significant in the pyridine process and it was remarkable that the residual of both blockers' derivatives would bring the potential risks on applications of lycopene products. Predominantly, durene met 0.35 mg/g DCW with imidazole and piperidine formaldehyde attained 0.24 mg/g DCW with pyridine after the end of lycopene fermentations.