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Background: The bone marrow is the place of hematopoiesis with a microenvironment that supports lifelong maintenance of stem cells and high proliferation. It is not surprising that this environment is also favourable for malignant cells emerging in the bone marrow or metastasizing to it. While the cellular composition of the bone marrow microenvironment has been extensively studied, the extracellular matrix and interstitial fluid components have received little attention. Since the sinusoids connect the bone marrow interstitial fluid to the circulation, it is often considered to have the same composition as peripheral blood plasma. Stark differences in the cellular composition of the bone marrow and peripheral blood with different secretory capacities would however suggest profound differences. Methods: In this study we set out to better define if and how the bone marrow interstitial fluid (BMIF) compares to the peripheral blood plasma (PBP) and how both are remodeled during chemotherapy. We applied a multi-omic strategy to quantify the metabolite, lipid and protein components as well as the proteolytic modification of proteins to gain a comprehensive understanding of the two compartments. Results: We found that the bone marrow interstitial fluid is clearly distinct from peripheral blood plasma, both during active pediatric acute lymphoblastic leukemia and following induction chemotherapy. Either compartment was shaped differently by active leukemia, with the bone marrow interstitial fluid being rich in extracellular vesicle components and showing protease dysregulation while the peripheral blood plasma showed elevation of immune regulatory proteins. Following chemotherapy, the BMIF showed signs of cellular remodeling and impaired innate immune activation while the peripheral blood plasma was characterized by restored lipid homeostasis. Conclusion: This study provides a comprehensive examination of the fluid portion of the acute lymphoblastic leukemia microenvironment and finds the contribution of either microenvironment to tumourigenesis. [ABSTRACT FROM AUTHOR]

Background: Salicylic acid (SA) is a phytohormone which works to regulate the abiotic stress response of plants. However, the molecular mechanism by which SA mediates heat tolerance in waxy maize (Zea mays L. sinsensis Kulesh) remains unknown. Results: Two varieties of waxy maize seedlings, heat-tolerant 'Yunuo7' (Y7) and heat-sensitive 'Suyunuo5' (S5), were pretreated with SA prior to heat stress (HTS). After treatment, physiological and transcriptomic changes were analyzed. Compared with HTS, the exogenous application of SA enhanced the shoot dry weight, the activities of antioxidant enzymes (e.g., SOD, POD, CAT and APX), and the concentration of endogenous phytohormones (e.g., SA, ABA, IAA, GA3), while decreased the MDA content. Transcriptome analysis showed that the number of differentially expressed genes (DEGs) identified in the control (CK) vs HTS and HTS vs HTS + SA comparisons were more in S5 than in Y7. HTS induced the downregulation of genes involved in photosynthesis and the upregulation of genes encoding heat shock transcription factors (HSFs) and heat shock proteins (HSPs). Compared with HTS, SA pretreatment reversed the expression of 5 photosynthesis-related genes, 26 phytohormone-related genes, and all genes encoding HSFs and HSPs in S5. Furthermore, the number of alternative splicing (AS) events increased under HTS treatment for both varieties, while decreased under SA pretreatment of S5. Differentially spliced genes (DSGs) showed little overlap with DEGs, and DEGs and DSGs differed significantly in functional enrichment. Conclusions: Physiological and transcriptional together indicated that HTS and SA pretreatment had a greater effect on S5 than Y7. Additionally, it appears that transcriptional regulation and AS work synergistically to enhance thermotolerance in heat-sensitive waxy maize. Our study revealed the regulatory effects and underlying molecular mechanisms of SA on waxy maize seedling under HTS. [ABSTRACT FROM AUTHOR]

Background: Remimazolam tosilate (HR7056, RT), a novel ultrashort-acting benzodiazepine, can be used for procedural sedation and general anaesthesia. However, few studies have focused on the sedative effect of RT during gastrointestinal endoscopy in elderly patients. The purpose of this study is to compare the sedative effect of RT and propofol for gastrointestinal endoscopy in elderly patients. Methods: A total of 82 patients aged ≥65 years with an American Society of Anaesthesiologists (ASA) grade I-II and a body mass index (BMI) of 18.0 to 30.0 kg/m2 who were scheduled for gastrointestinal endoscopy from Jan 2021 to Aug 2021 were selected and randomly divided into a RT group and a propofol group. Alfentanil 5 μg/kg was used for analgesia in both groups. The RT group was given remimazolam tosilate 0.15 mg/kg with supplemental doses of 0.05 mg/kg as need, while the propofol group was given propofol 1.5 mg/kg with supplemental doses of 0.5 mg/kg. The supplemental doses were determined by the modified observational alertness/sedation assessment (MOAA/S) score and the patients' body movements. Sedative effects, such as the time to loss of consciousness (LOC) (MOAA/S score ≤ 1), successful sedation in one dose, number of supplemental doses after successful induction, and recovery time, were evaluated. Sedation-related side effects, such as injection pain, haemodynamic events and respiratory depression, were also noted. Postoperative nausea and vomiting (PONV), visual analogue scale (VAS) scores at rest, remedial analgesics, and dizziness or headache were recorded. In addition, patients' satisfaction and physician's satisfaction of the procedure were compared between the two groups. Results: Data from 77 patients were analysed. The success rate of sedation in both groups was 100%. The time to LOC (MOAA/S score ≤ 1) in the RT group was longer than that in the propofol group (20.7 ± 6.1s vs. 13.2 ± 5.2s, P < 0.001). There were fewer patients in the RT group reporting injection pain than that in the propofol group (0/39 vs. 5/38, P = 0.025). Haemodynamic events and respiratory depression in the RT group were less frequent than those in the propofol group ((6/39 vs. 17/38, P = 0.005), (2/39 vs. 9/38, P = 0.026), respectively). The number of supplemental doses after successful induction in the RT group was greater than that in the propofol group (4/9/11/13/1/1 vs. 8/4/18/6/2/0 requiring 0, 1, 2, 3, 4 or 5 supplemental doses, P = 0.014). The characteristics of the patients enrolled, postoperative parameters of the patients, and patients' and physician's satisfaction of the procedure were comparable in the two groups. Conclusions: Compared with propofol, RT can be safely and effectively used for gastrointestinal endoscopy sedation in elderly patients, and the incidence of sedation-related adverse reactions, especially haemodynamic events and respiratory depression, is lower. When RT is used, the number of supplemental doses after successful induction may increase slightly. Trial registration: Chictr.org.cn ChiCTR2000040498. Retrospectively registered (date of registration: December 1, 2020). [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs) deteriorate tumor microenvironment (TME) and hinder intra-tumoral drug delivery. Direct depleting CAFs exists unpredictable risks of tumor metastasis. Epithelial–mesenchymal transition (EMT) is a critical process of CAFs converted from hepatic stellate cells during hepatocellular tumorigenesis; however, until now the feasibility of reversing EMT to battle hepatocellular carcinoma has not been comprehensively explored. In this study, we report a CFH peptide (CFHKHKSPALSPVGGG)-decorated liposomal oxymatrine (CFH/OM-L) with a high affinity to Tenascin-C for targeted inactivating CAFs through reversing EMT, which is verified by the upregulation of E-cadherin and downregulation of vimentin, N-cadherin, and snail protein in vivo and in vitro. After the combination with icaritin-loaded lipid complex, CFH/OM-L obviously boosts the comprehensive anticancer efficacy in both 3D tumor spheroids and stromal-rich tumor xenograft nude mouse models. The combinational therapy not only effectively reversed the in vivo EMT process but also significantly lowered the collagen, creating favorable conditions for deep penetration of nanoparticles. More importantly, CFH/OM-L does not kill but inactivates CAFs, resulting in not only a low risk of tumor metastasis but also a reprogramming TME, such as M1 tumor-associated macrophages polarization and natural killer cells activation. Such strategy paves a moderate way to remold TME without depleting CAFs and provides a powerful tool to design strategies of combinational hepatocellular carcinoma therapy. [ABSTRACT FROM AUTHOR]

Background: China has made tremendous progresses in serving the needs of its people living with rare diseases in the past decade, especially over the last 5 years. The Chinese government's systematic approach included a series of coordinated initiatives, amongst these are: forming the Rare Disease Expert Committee (2016), funding the "Rare Diseases Cohort Study" (2016-2020), and publishing its first "Rare Disease Catalog" (2018). Herein, we present the National Rare Diseases Registry System (NRDRS)-China's first national rare diseases registry, and the analysis of cases registered in the first 5 years ending Dec 31, 2020.Results: The total 62,590 cases covered 166 disease/disease types, forming 183 disease cohorts. The data from nearly 22% of them (13,947 cases) is also linked to valuable biological samples. The average age of definitive diagnosis was 30.88 years; 36.07% of cases were under 18 years of age. Regional distribution analysis showed 60% of cases were from the more developed, wealthier East and North China, suggesting the local availability of quality care and patients' financial status were key access factors. Finally, 82.04% of cases were registered from the five clinical departments: Neurology, Endocrine, Hematology, Cardiovascular, and Nephrology, suggesting that either these are most affected by rare diseases, or that there were disease non-specific ascertainment factors.Conclusions: The preliminary analysis of the first 5-year's data provides unique and valuable insight on rare disease distribution in China, and higlights the directions for enhancing equity, scale and utility. [ABSTRACT FROM AUTHOR]

Background: Currently, automatic esophagus segmentation remains a challenging task due to its small size, low contrast, and large shape variation. We aimed to improve the performance of esophagus segmentation in deep learning by applying a strategy that involves locating the object first and then performing the segmentation task. Methods: A total of 100 cases with thoracic computed tomography scans from two publicly available datasets were used in this study. A modified CenterNet, an object location network, was employed to locate the center of the esophagus for each slice. Subsequently, the 3D U-net and 2D U-net_coarse models were trained to segment the esophagus based on the predicted object center. A 2D U-net_fine model was trained based on the updated object center according to the 3D U-net model. The dice similarity coefficient and the 95% Hausdorff distance were used as quantitative evaluation indexes for the delineation performance. The characteristics of the automatically delineated esophageal contours by the 2D U-net and 3D U-net models were summarized. Additionally, the impact of the accuracy of object localization on the delineation performance was analyzed. Finally, the delineation performance in different segments of the esophagus was also summarized. Results: The mean dice coefficient of the 3D U-net, 2D U-net_coarse, and 2D U-net_fine models were 0.77, 0.81, and 0.82, respectively. The 95% Hausdorff distance for the above models was 6.55, 3.57, and 3.76, respectively. Compared with the 2D U-net, the 3D U-net has a lower incidence of delineating wrong objects and a higher incidence of missing objects. After using the fine object center, the average dice coefficient was improved by 5.5% in the cases with a dice coefficient less than 0.75, while that value was only 0.3% in the cases with a dice coefficient greater than 0.75. The dice coefficients were lower for the esophagus between the orifice of the inferior and the pulmonary bifurcation compared with the other regions. Conclusion: The 3D U-net model tended to delineate fewer incorrect objects but also miss more objects. Two-stage strategy with accurate object location could enhance the robustness of the segmentation model and significantly improve the esophageal delineation performance, especially for cases with poor delineation results. [ABSTRACT FROM AUTHOR]

Background: Kernel development and starch formation are the primary determinants of maize yield and quality, which are considerably influenced by drought stress. To clarify the response of maize kernel to drought stress, we established well-watered (WW) and water-stressed (WS) conditions at 1–30 days after pollination (dap) on waxy maize (Zea mays L. sinensis Kulesh). Results: Kernel development, starch accumulation, and activities of starch biosynthetic enzymes were significantly reduced by drought stress. The morphology of starch granules changed, whereas the grain filling rate was accelerated. A comparative proteomics approach was applied to analyze the proteome change in kernels under two treatments at 10 dap and 25 dap. Under the WS conditions, 487 and 465 differentially accumulated proteins (DAPs) were identified at 10 dap and 25 dap, respectively. Drought induced the downregulation of proteins involved in the oxidation–reduction process and oxidoreductase, peroxidase, catalase, glutamine synthetase, abscisic acid stress ripening 1, and lipoxygenase, which might be an important reason for the effect of drought stress on kernel development. Notably, several proteins involved in waxy maize endosperm and starch biosynthesis were upregulated at early-kernel stage under WS conditions, which might have accelerated endosperm development and starch synthesis. Additionally, 17 and 11 common DAPs were sustained in the upregulated and downregulated DAP groups, respectively, at 10 dap and 25 dap. Among these 28 proteins, four maize homologs (i.e., A0A1D6H543, B4FTP0, B6SLJ0, and A0A1D6H5J5) were considered as candidate proteins that affected kernel development and drought stress response by comparing with the rice genome. Conclusions: The proteomic changes caused by drought were highly correlated with kernel development and starch accumulation, which were closely related to the final yield and quality of waxy maize. Our results provided a foundation for the enhanced understanding of kernel development and starch formation in response to drought stress in waxy maize. [ABSTRACT FROM AUTHOR]

Background: Accumulation of alpha-synuclein (α-syn) is a main pathological hallmark of Parkinson's and related diseases, which are collectively known as synucleinopathies. Growing evidence has supported that the same protein can induce remarkably distinct pathological progresses and disease phenotypes, suggesting the existence of strain difference among α-syn fibrils. Previous studies have shown that α-syn pathology can propagate from the peripheral nervous system (PNS) to the central nervous system (CNS) in a "prion-like" manner. However, the difference of the propagation potency from the periphery to CNS among different α-syn strains remains unknown and the effect of different generation processes of these strains on the potency of seeding and propagation remains to be revealed in more detail. Methods: Three strains of preformed α-syn fibrils (PFFs) were generated in different buffer conditions which varied in pH and ionic concentrations. The α-syn PFFs were intramuscularly (IM) injected into a novel bacterial artificial chromosome (BAC) transgenic mouse line that expresses wild-type human α-syn, and the efficiency of seeding and propagation of these PFFs from the PNS to the CNS was evaluated. Results: The three strains of α-syn PFFs triggered distinct propagation patterns. The fibrils generated in mildly acidic buffer led to the most severe α-syn pathology, degeneration of motor neurons and microgliosis in the spinal cord. Conclusions: The different α-syn conformers generated in different conditions exhibited strain-specific pathology and propagation patterns from the periphery to the CNS, which further supports the view that α-syn strains may be responsible for the heterogeneity of pathological features and disease progresses among synucleinopathies. [ABSTRACT FROM AUTHOR]

Background: The Surgical Pleth Index (SPI) is an objective tool that can reflect nociception-antinociception balance and guide the use of intraoperative analgesics. Multimodal analgesia has been neglected in many previous studies. The aim of this study was to compare fentanyl consumption using SPI-guided analgesia versus conventional analgesia techniques under multimodal analgesia in laparoscopic cholecystectomy. Methods: A total of 80 patients aged 18–65 years with American Society of Anaesthesiologists (ASA) grade I-II and a body mass index (BMI) of 18.5 to 30 kg/m2 who were scheduled for laparoscopic cholecystectomy under total intravenous anaesthesia from March 2020 to September 2020 were selected. Multimodal analgesia, including local infiltration of the surgical incision, nonsteroidal anti-inflammatory drugs and opioids, was adopted perioperatively. Fentanyl boluses of 1.0 µg/kg were administered to maintain the SPI value between 20 and 50 in the SPI group. By contrast, fentanyl boluses of 1.0 µg/kg were administered whenever the heart rate (HR) or mean arterial pressure (MAP) increased to 20 % above baseline or when the HR was greater than 90 beats per minute (bpm) in the control group. Preoperative and postoperative blood glucose, plasma cortisol and interleukin-6 (IL-6) levels were evaluated. Intraoperative haemodynamic events and propofol and fentanyl doses were noted. The extubation time, postoperative visual analogue scale (VAS) score, use of remedial analgesics and opioid-related adverse reactions were recorded. Results: In total, 18 of 80 patients withdrew for various reasons, and data from 62 patients were finally analysed. Intraoperative fentanyl consumption was significantly lower in the SPI group than in the control group (177.1 ± 65.9 vs. 213.5 ± 47.5, P = 0.016). The postoperative extubation time was shorter in the SPI group than in the control group (16.1 ± 5.2 vs. 22.1 ± 6.3, P < 0.001). Preoperative and postoperative blood glucose, plasma cortisol and IL-6 levels, intraoperative haemodynamic changes, postoperative VAS scores, remedial analgesic consumption and opioid-related adverse reactions were comparable in the two groups. Conclusions: Lower doses of fentanyl are required intraoperatively with shorter extubation times when SPI is used to guide intraoperative analgesia compared to conventional analgesia techniques under multimodal analgesia in laparoscopic cholecystectomy. Trial registration: Chictr.org.cn ChiCTR2000030145. Retrospectively Registered (Date of registration: February 24, 2020). [ABSTRACT FROM AUTHOR]

Background: It has been proposed that the dose of rescue opioids should be individually titrated to the severity of obstructive sleep apnea after adenotonsillectomy. However, a sleep study is not always available before adenotonsillectomy. This randomized, controlled and blinded trial evaluated a strategy of pain control individualized to the results of a fentanyl test, rather than the results of polysomnography, in children after adenotonsillectomy. Methods: A total of 280 children (3–10 years old) undergoing elective adenotonsillectomy were randomized into an individualized protocol (IP) group or a conservative protocol (CP) group. All patients received a fentanyl test before extubation. Pain was assessed every 10 min in the recovery room, and rescue morphine was given when the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) score was > 6. In the IP group, the dose of rescue morphine was individualized to the results of the fentanyl test (10 μg/kg in the case of a positive result and 50 μg/kg in the case of a negative result). In the CP group, the dose was fixed (25 μg/kg). The primary outcome was the percentage of patients requiring at least one medical intervention. The secondary outcome was the median duration of CHEOPS scores > 6. Results: Fewer patients in the IP group than in the CP group required medical interventions [11.9% (16/134) vs 22.3% (29/130), P = 0.025]. The median duration of CHEOPS scores > 6 was shorter in the IP group than in the CP group [20 (95% CI: 17 to 23) min vs 30 (95% CI: 28 to 32) min, P < 0.001]. Conclusions: Compared with a conservative dosing approach, this individualized protocol may improve analgesia without a significant increase in respiratory adverse events. Trial registration: ClinicalTrials.gov NCT02990910, registered on 13/12/2016. [ABSTRACT FROM AUTHOR]

Background: Fruit abortion is a major limiting factor for fruit production. In flat peach, fruit abortion is present in the whole tree of some accessions during early fruit development. However, the physiological factors and genetic mechanism underlying flat fruit abortion remain largely elusive. Results: In this study, we have revealed that the fertilization process was accomplished and the reduction of sucrose and starch contents might result in flat fruit abortion. By combining association and gene expression analysis, a key candidate gene, PpSnRK1βγ, was identified. A 1.67-Mb inversion co-segregated with flat fruit shape altered the promoter activity of PpSnRK1βγ, resulting in much lower expression in aborting flat peach. Ectopic transformation in tomato and transient overexpression in peach fruit have shown that PpSnRK1βγ could increase sugar and starch contents. Comparative transcriptome analysis further confirmed that PpSnRK1βγ participated in carbohydrate metabolism. Subcellular localization found that PpSnRK1βγ was located in nucleus. Conclusions: This study provides a possible reason for flat fruit abortion and identified a critical candidate gene, PpSnRK1βγ, that might be responsible for flat fruit abortion in peach. The results will provide great help in peach breeding and facilitate gene identification for fruit abortion in other plant species. [ABSTRACT FROM AUTHOR]

Background: Human hydatid disease typically occurs in organs such as the liver and kidney. Primary solitary intramuscular hydatid disease, however, is rare. Case Presentation: We report a case of a giant muscle hydatid in the lower extremity, with neurological symptoms as the first manifestation. The symptoms specifically manifested as intermittent pain in the right lower extremity and numbness in the sole of the right foot. However, there were no obvious abnormalities detected in electromyography and lumbar MRI. Subsequent ultrasonography and calf MRI showed that the patient had cystic lesions in the calf. The patient was initially diagnosed with a muscle hydatid cyst. Treatment involved complete surgical excision of the lesion, and the diagnosis of a hydatid cyst was confirmed through macroscopic and microscopic histopathological examination after the mass was excised. The patient was given oral albendazole, and no recurrence was observed during the 12 months of follow-up. Conclusions: This case underscores the need to consider hydatid disease when diagnosing soft tissue masses in muscles, particularly in endemic areas. Patients may initially present with atypical symptoms like peripheral nerve issues. [ABSTRACT FROM AUTHOR]

Introduction: Herpes simplex virus is the most common cause of sporadic viral encephalitis. Cognitive impairments persist in most patients who survive herpes simplex virus-caused encephalitis after undergoing currently available treatments. This is the first report on the development of human cord blood-derived mononuclear cell transplantation as a new treatment intervention to improve the prognosis of sequelae of viral encephalitis.Case Presentation: An 11-year-old Han Chinese boy developed sequelae of viral encephalitis with cognitive, mental and motor impairments in the 8 months following routine treatments. Since receiving allogeneic cord blood-derived mononuclear cell transplantation combined with comprehensive rehabilitation therapies 7 years ago, the patient's health has significantly improved and remained stable.Conclusions: Human cord blood-derived mononuclear cell transplantation may be a potential therapeutic strategy for treating the neuropsychiatric and neurobehavioral sequelae of viral encephalitis. [ABSTRACT FROM AUTHOR]

Background: Anesthesia and surgery can induce perioperative neurocognitive disorders (PND). Mitochondrial dysfunction has been proposed to be one of the earliest triggering events in surgery-induced neuronal damage. Dexmedetomidine has been demonstrated to attenuate the impairment of cognition in aged rats induced by surgery in our previous study. Methods: Male Sprague-Dawley rats underwent hepatic apex resection under anesthesia with propofol to clinically mimic human abdominal surgery. The rats were divided into three groups: Control group, Model group and Dexmedetomidine (Dex) group. Cognitive function was evaluated with the Morris water maze (MWM), Open Field Test (OFT)and Novel object recognition task (NOR). Ultrastructural change in neuronal mitochondria was measured by transmission electron microscopy. Mitochondrial function was measured by mitochondrial membrane potential and activities of mitochondrial complexes. Neuronal morphology was observed with H&E staining and the activation of glial cells was observed by immunohistochemistry in the hippocampus. Protein levels were measured by Western blot (WB) and immunofluorescence at 3 and 7 days after surgery. Results: Surgery-induced cognitive decline lasts three days, but not seven days after surgery in the model group. Transmission electron microscope showed the mitochondrial structure damage in the model group, similar changes were not induced in the Dex group. Dexmedetomidine may reverse the decrease in mitochondrial membrane potential and mitochondrial complex activity. Compared with the Control group, the expression of cytochrome c was significantly increased in model group by Western blot and immunofluorescence on days 3, but not day 7. Rats from the Model group expressed significantly greater levels of Iba-1 and GFAP compared with the Control group and the Dex group. Conclusion: Dexmedetomidine appears to reverse surgery-induced behavior, mitigate the higher density of Iba-1 and GFAP, reduce the damage of mitochondrial structure and function by alleviating oxidative stress and protect mitochondrial respiratory chain, thus increasing cytochrome c oxidase (COX) expression and downregulate the expression of cytochrome c protein in the hippocampus of rats. [ABSTRACT FROM AUTHOR]

Background: Antagonists of growth hormone-releasing hormone (GHRH) are being developed for the treatment of various human cancers. Methods: MTT assay was used to test the proliferation of SKOV3 and CaOV3. The splice variant expression of GHRH receptors was examined by RT-PCR. The expression of protein in signal pathway was examined by Western blotting. siRNA was used to block the effect of EGFR. Results: In this study, we investigated the effects of a new GHRH antagonist JMR-132, in ovarian cancer cell lines SKOV3 and CaOV3 expressing splice variant (SV)1 of GHRH receptors. MTT assay showed that JMR-132 had strong antiproliferative effects on SKOV3 and CaOV3 cells in both a time-dependent and dose-dependent fashion. JMR-132 also induced the activation and increased cleaved caspase3 in a time- and dose-dependent manner in both cell lines. In addition, JMR-132 treatments decreased significantly the epidermal growth factor receptor (EGFR) level and the phosphorylation of Akt (p-Akt), suggesting that JMR-132 inhibits the EGFR-Akt pathway in ovarian cancer cells. More importantly, treatment of SKOV3 and CaOV3 cells with 100 nM JMR-132 attenuated proliferation and the antiapoptotic effect induced by EGF in both cell lines. After the knockdown of the expression of EGFR by siRNA, the antiproliferative effect of JMR-132 was abolished in SKOV3 and CaOV3 cells. Conclusions: The present study demonstrates that the inhibitory effect of the GHRH antagonist JMR-132 on proliferation is due, in part, to an interference with the EGFR-Akt pathway in ovarian cancer cells. [ABSTRACT FROM AUTHOR]

Background: Tumor cells tend to utilize glycolysis rather than aerobic respiration even under aerobic conditions. OVOL2, an inhibitory C2H2 zinc finger transcription factor, is a potential tumor suppressor in cancers. However, the association between OVOL2 and tumor energy metabolism is unknown. Methods: Western blotting was used to determine the expression of OVOL2 in different non-small cell lung cancer (NSCLC) cell lines and mouse models. The metabolic parameters in NSCLC cells following overexpression or knockdown OVOL2 were examined. To define the mechanism by which OVOL2 regulates aerobic glycolysis, interacting protein of OVOl2 and downstream molecular events were identified by luciferase assay and co-immunoprecipitation. We documented the regulatory mechanism in mouse xenograft models. Finally, clinical relevance of OVOL2, NF-κB signaling and GLUT1 was measured by immunostaining. Results: OVOL2 is downregulated in NSCLC and overexpression of OVOL2 inhibits the survival of cancer cells. Moreover, OVOL2 directly binds to P65 and inhibits the recruitment of P300 but facilitates the binding of HDAC1 to P65, which in turn negatively regulates NF-κB signaling to suppress GLUT1 translocation and glucose import. In contrast, OVOL2 expression is negatively regulated by NF-κB signaling in NSCLC cells via the ubiquitin–proteasome pathway. Re-expression of OVOL2 significantly compromise NF-κB signaling-induced GLUT1 translocation, aerobic glycolysis in NSCLC cells and mouse models. Immunostaining revealed inverse correlations between the OVOL2 and phosphorylated P65 levels and between the OVOL2 and membrane GLUT1 levels, and a strong correlation between the phosphorylated P65 and membrane GLUT1 levels. Conclusions: These results suggest a regulatory circuit linking NF-κB and OVOL2, which highlights the role of NF-κB signaling and OVOL2 in the modulation of glucose metabolism in NSCLC. 5S647uSA4FfDHArbVFhiZ4 Video Abstract [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to establish a methodology for determining carboxymethyl lysine (CML) and carboxyethyl lysine (CEL) concentrations in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The test results were also used for clinical aging research. Methods: Human plasma samples were incubated with aqueous perfluorovaleric acid (NFPA), succeeded by precipitation utilizing trichloroacetic acid, hydrolysis facilitated by hydrochloric acid, nitrogen drying, and ultimate re-dissolution utilizing NFPA, followed by filtration. Cotinine-D3 was added as an internal standard. The separation was performed on an Agela Venusil ASB C18 column (50 mm × 4.6 mm, 5 μm) with a 5 mmol/L NFPA and acetonitrile/water of 60:40 (v/v) containing 0.15% formic acid. The multiple reaction monitoring mode was used for detecting CML, CEL, and cotinine-D3, with ion pairs m/z 205.2 > 84.1 (for quantitative) and m/z 205.2 > m/z 130.0 for CML, m/z 219.1 > 84.1 (for quantitative) and m/z 219.1 > m/z 130.1 for CEL, and m/z 180.1 > 80.1 for cotinine-D3, respectively. Results: The separation of CML and CEL was accomplished within a total analysis time of 6 minutes. The retention times of CML, CEL, and cotinine-D3 were 3.43 minutes, 3.46 minutes, and 4.50 minutes, respectively. The assay exhibited linearity in the concentration range of 0.025–1.500 μmol/L, with a lower limit of quantification of 0.025 μmol/L for both compounds. The relative standard deviations of intra-day and inter-day were both below 9%, and the relative errors were both within the range of ±4%. The average recoveries were 94.24% for CML and 97.89% for CEL. Conclusion: The results indicate that the developed methodology is fast, highly sensitive, highly specific, reproducible, and suitable for the rapid detection of CML and CEL in clinical human plasma samples. The outcomes of the clinical research project on aging underscored the important indicative significance of these two indicators for research on human aging. [ABSTRACT FROM AUTHOR]

Background: Mutations in MPZL2, the characteristic genetic etiology of autosomal recessive deafness loci 111 (DFNB111), cause non-syndromic and moderate sensorineural hearing loss. Methods: In this study, we analyzed the phenotype and genotype of eight pedigrees consisting of 10 hearing loss patients with bi-allelic pathogenic or likely pathogenic variants in MPZL2. These patients were identified from a 3272 Chinese patient cohort who underwent genetic testing. Results: Apart from symmetrical and moderate sensorineural hearing loss, the MPZL2-related phenotype was characterized by progressive hearing loss with variation in the onset age (congenital defect to onset at the young adult stage). We determined that in the Chinese population, the genetic load of MPZL2 defects was 0.24% (8/3272) in patients diagnosed with hearing loss and 7.02% (8/114) in patients diagnosed with hereditary moderate sensorineural hearing loss caused by STRC, OTOA, OTOG, OTOGL, TECTA, MPZL2 and others. Three known MPZL2 variants (c.220C > T (p.Gln74*), c.68delC (p.Pro23Leufs*2), c.463delG (p.Ala155Leufs*10)) and a novel start loss variant (c.3G > T (p.Met1?)) were identified. MPZL2 c.220C > T was identified as the hotspot variant in the Chinese population and even in East Asia compared with c.72delA (p.Ile24Metfs*22) in European and West Asia through allele frequency. Conclusions: We concluded that apart from moderate HL, progressive HL is another character of MPZL2-related HL. No specified variant was verified for the progression of HL, the penetrance and expressivity cannot be determined yet. A novel MPZL2 variant at the start codon was identified, enriching the variant spectrum of MPZL2. The hotspot variants of MPZL2 vary in different ethnicities. This study provides valuable data for the diagnosis, prognosis evaluation and genetic counseling of patients with moderate sensorineural hearing loss related to MPZL2. [ABSTRACT FROM AUTHOR]

Periodontitis is a chronic inflammatory disease caused by the local microbiome and the host immune response, resulting in periodontal structure damage and even tooth loss. Scaling and root planning combined with antibiotics are the conventional means of nonsurgical treatment of periodontitis, but they are insufficient to fully heal periodontitis due to intractable bacterial attachment and drug resistance. Novel and effective therapeutic options in clinical drug therapy remain scarce. Nanotherapeutics achieve stable cell targeting, oral retention and smart release by great flexibility in changing the chemical composition or physical characteristics of nanoparticles. Meanwhile, the protectiveness and high surface area to volume ratio of nanoparticles enable high drug loading, ensuring a remarkable therapeutic efficacy. Currently, the combination of advanced nanoparticles and novel therapeutic strategies is the most active research area in periodontitis treatment. In this review, we first introduce the pathogenesis of periodontitis, and then summarize the state-of-the-art nanotherapeutic strategies based on the triple concerto of antibacterial activity, immunomodulation and periodontium regeneration, particularly focusing on the therapeutic mechanism and ingenious design of nanomedicines. Finally, the challenges and prospects of nano therapy for periodontitis are discussed from the perspective of current treatment problems and future development trends. [ABSTRACT FROM AUTHOR]

Background: Impaired wound healing frequently occurs in diabetes mellitus (DM) and is implicated in impaired angiogenesis. Long non-coding RNA (lncRNA) H19 has been reported as being reduced in DM and played a critical role in inducing angiogenesis. Thus, we hypothesized that H19 may affect impaired wound healing in streptozotocin (STZ)-induced diabetic mice transfused with autologous blood preserved in standard preservative fluid or modified preservative fluid. Methods: Fibroblasts in injured skin were isolated and cultured in vitro. After location of H19 in fibroblasts using fluorescence in situ hybridization (FISH), RNA-pull down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), Co immunoprecipitation (COIP) and dual luciferase reporter gene assay were used to verify the binding of H19 to HIF-1α. Results: The modified preservative fluid preserved autologous blood increased the H19 expression in fibroblasts, and maintained better oxygen-carrying and oxygen release capacities as well as coagulation function. Furthermore, H19 promoted HIF-1α histone H3K4me3 methylation and increased HIF-1α expression by recruiting EZH2. H19 promoted fibroblast activation by activating HIF-1α signaling pathway in fibroblasts and enhanced wound healing in diabetic mice. Conclusions: Taken together, H19 accelerated fibroblast activation by recruiting EZH2-mediated histone methylation and modulating the HIF-1α signaling pathway, whereby augmenting the process of modified preservative fluid preserved autologous blood enhancing the postoperative wound healing in diabetic mice. [ABSTRACT FROM AUTHOR]

Background: Laminitis is a common and serve disease which caused by inflammation and pathological changes of the laminar junction. However, the pathologic mechanism remains unclear. In this study we aimed to investigate changes of the gut microbiota and metabolomics in oligofructose-induced laminitis of horses. Results: Animals submitted to treatment with oligofructose had lower fecal pH but higher lactic acid, histamine, and Lipopolysaccharide (LPS) in serum. Meanwhile, oligofructose altered composition of the hindgut bacterial community, demonstrated by increasing relative abundance of Lactobacillus and Megasphaera. In addition, the metabolome analysis revealed that treatment with oligofructose decreased 84 metabolites while 53 metabolites increased, such as dihydrothymine, N3,N4-Dimethyl-L-arginine, 10E,12Z-Octadecadienoic acid, and asparagine. Pathway analysis revealed that aldosterone synthesis and secretion, regulation of lipolysis in adipocytes, steroid hormone biosynthesis, pyrimidine metabolism, biosynthesis of unsaturated fatty acids, and galactose metabolism were significantly different between healthy and laminitis horses. Furthermore, correlation analysis between gut microbiota and metabolites indicated that Lactobacillus and/or Megasphaera were positively associated with the dihydrothymine, N3,N4-Dimethyl-L-arginine, 10E,12Z-Octadecadienoic acid, and asparagine. Conclusions: These results revealed that disturbance of gut microbiota and changes of metabolites were occurred during the development of equine laminitis, and these results may provide novel insights to detect biomarkers for a better understanding of the potential mechanism and prevention strategies for laminitis in horses. [ABSTRACT FROM AUTHOR]

Resistance genes (R genes) are a class of genes that are immune to a wide range of diseases and pests. In planta, NLR genes are essential components of the innate immune system. Currently, genes belonging to NLR family have been found in a number of plant species, but little is known in peach. Here, 286 NLR genes were identified on peach genome by using their homologous genes in Arabidopsis thaliana as queries. These 286 NLR genes contained at least one NBS domain and LRR domain. Phylogenetic and N-terminal domain analysis showed that these NLRs could be separated into four subfamilies (I-IV) and their promoters contained many cis-elements in response to defense and phytohormones. In addition, transcriptome analysis showed that 22 NLR genes were up-regulated after infected by Green Peach Aphid (GPA), and showed different expression patterns. This study clarified the NLR gene family and their potential functions in aphid resistance process. The candidate NLR genes might be useful in illustrating the mechanism of aphid resistance in peach. [ABSTRACT FROM AUTHOR]

Background: In the context of climate change, maize is facing unprecedented heat stress (HS) threats during grain filling. Understanding how HS affects yield is the key to reducing the impact of climate change on maize production. Suyunuo5 (SYN5) and Yunuo7 (YN7) were used as materials, and four temperature gradients of 28℃ (day)/20℃ (night; T0, control), 32 °C/24°C (T1, mild HS), 36 °C/28°C (T2, moderate HS), and 40 °C/32°C (T3, severe HS) were set up during grain filling to explore the physiological mechanism of different degrees HS affecting photosynthetic characteristics of leaves in this study. Results: Results showed that HS accelerated the degradation of chlorophyll, disturbed the metabolism of reactive oxygen species, reduced the activity of antioxidant enzymes, and caused leaf damage. Heat stress induced the down-regulation of photosynthesis-related genes, which results in the decrease of enzymatic activities involved in photosynthesis, thereby inhibiting photosynthesis and reducing yield. Integrated analysis showed that the degree of the negative influence of three HS types during grain filling on leaves and yield was T3 > T2 > T1. The increase in HS disturbed leaf physiological activities and grain filling. Meanwhile, this study observed that the YN7 was more heat tolerance than SYN5 and thus it was recommended to use YN7 in waxy maize planting areas with frequent high temperatures. Conclusions: Heat stress during grain filling caused premature senescence of the leaves by inhibiting the ability of leaves to photosynthesize and accelerating the oxidative damage of cells, thereby affecting the waxy maize yield. Our study helped to simulate the productivity of waxy maize under high temperatures and provided assistance for a stable yield of waxy maize under future climate warming. [ABSTRACT FROM AUTHOR]

Background: Antigens expressed in sexual stages of the malaria parasites are targets of transmission-blocking vaccines (TBVs). HAP2/GCS1, a TBV candidate, is critical for fertilization in Plasmodium. Here, the genetic diversity of PvHAP2 was studied in Plasmodium vivax parasite populations from the Greater Mekong Subregion (GMS). Methods: Plasmodium vivax clinical isolates were collected in clinics from the China-Myanmar border region (135 samples), western Thailand (41 samples) and western Myanmar (51 samples). Near full-length Pvhap2 (nucleotides 13–2574) was amplified and sequenced from these isolates. Molecular evolution studies were conducted to evaluate the genetic diversity, selection and population differentiation. Results: Sequencing of the pvhap2 gene for a total of 227 samples from the three P. vivax populations revealed limited genetic diversity of this gene in the GMS (π = 0.00036 ± 0.00003), with the highest π value observed in Myanmar (0.00053 ± 0.00009). Y133S was the dominant mutation in the China-Myanmar border (99.26%), Myanmar (100%) and Thailand (95.12%). Results of all neutrality tests were negative for all the three populations, suggesting the possible action of purifying selection. Codon-based tests identified specific codons which are under purifying or positive selections. Wright's fixation index showed low to moderate genetic differentiation of P. vivax populations in the GMS, with FST ranging from 0.04077 to 0.24833, whereas high levels of genetic differentiation were detected between the China-Myanmar border and Iran populations (FST = 0.60266), and between Thailand and Iran populations (FST = 0.44161). A total of 20 haplotypes were identified, with H2 being the abundant haplotype in China-Myanmar border, Myanmar and Thailand populations. Epitope mapping prediction of Pvhap2 antigen showed that high-score B-cell epitopes are located in the S307-G324, L429-P453 and V623-D637 regions. The E317K and D637N mutations located within S307-G324 and V623-D637 epitopes slightly reduced the predicted score for potential epitopes. Conclusions: The present study showed a very low level of genetic diversity of pvhap2 gene among P. vivax populations in the Greater Mekong Subregion. The relative conservation of pvhap2 supports further evaluation of a Pvhap2-based TBV. [ABSTRACT FROM AUTHOR]

Background: The malaria elimination plan of the Greater Mekong Subregion (GMS) is jeopardized by the increasing number of Plasmodium vivax infections and emergence of parasite strains with reduced susceptibility to the frontline drug treatment chloroquine/primaquine. This study aimed to determine the evolution of the P. vivax multidrug resistance 1 (Pvmdr1) gene in P. vivax parasites isolated from the China–Myanmar border area during the major phase of elimination. Methods: Clinical isolates were collected from 275 P. vivax patients in 2008, 2012–2013 and 2015 in the China–Myanmar border area and from 55 patients in central China. Comparison was made with parasites from three border regions of Thailand. Results: Overall, genetic diversity of the Pvmdr1 was relatively high in all border regions, and over the seven years in the China–Myanmar border, though slight temporal fluctuation was observed. Single nucleotide polymorphisms previously implicated in reduced chloroquine sensitivity were detected. In particular, M908L approached fixation in the China–Myanmar border area. The Y976F mutation sharply decreased from 18.5% in 2008 to 1.5% in 2012–2013 and disappeared in 2015, whereas F1076L steadily increased from 33.3% in 2008 to 77.8% in 2015. While neutrality tests suggested the action of purifying selection on the pvmdr1 gene, several likelihood-based algorithms detected positive as well as purifying selections operating on specific amino acids including M908L, T958M and F1076L. Fixation and selection of the nonsynonymous mutations are differently distributed across the three border regions and central China. Comparison with the global P. vivax populations clearly indicated clustering of haplotypes according to geographic locations. It is noteworthy that the temperate-zone parasites from central China were completely separated from the parasites from other parts of the GMS. Conclusions: This study showed that P. vivax populations in the China–Myanmar border has experienced major changes in the Pvmdr1 residues proposed to be associated with chloroquine resistance, suggesting that drug selection may play an important role in the evolution of this gene in the parasite populations. [ABSTRACT FROM AUTHOR]

Background: Aureobasidium pullulans is a yeast-like fungus that can ferment xylose to generate high-value-added products, such as pullulan, heavy oil, and melanin. The combinatorial expression of two xylose reductase (XR) genes and two xylitol dehydrogenase (XDH) genes from Spathaspora passalidarum and the heterologous expression of the Piromyces sp. xylose isomerase (XI) gene were induced in A. pullulans to increase the consumption capability of A. pullulans on xylose. Results: The overexpression of XYL1.2 (encoding XR) and XYL2.2 (encoding XDH) was the most beneficial for xylose utilization, resulting in a 17.76% increase in consumed xylose compared with the parent strain, whereas the introduction of the Piromyces sp. XI pathway failed to enhance xylose utilization efficiency. Mutants with superior xylose fermentation performance exhibited increased intracellular reducing equivalents. The fermentation performance of all recombinant strains was not affected when glucose or sucrose was utilized as the carbon source. The strain with overexpression of XYL1.2 and XYL2.2 exhibited excellent fermentation performance with mimicked hydrolysate, and pullulan production increased by 97.72% compared with that of the parent strain. Conclusions: The present work indicates that the P4 mutant (using the XR/XDH pathway) with overexpressed XYL1.2 and XYL2.2 exhibited the best xylose fermentation performance. The P4 strain showed the highest intracellular reducing equivalents and XR and XDH activity, with consequently improved pullulan productivity and reduced melanin production. This valuable development in aerobic fermentation by the P4 strain may provide guidance for the biotransformation of xylose to high-value products by A. pullulans through genetic approach. [ABSTRACT FROM AUTHOR]

Background: Conventional perioperative analgesic modalities (e.g. opioids, epidural analgesia) have their own drawbacks, which limit their clinical application. This study investigated the opioid-sparing effectsof the oblique subcostal transversus abdominis plane (OSTAP) blockade with ropivacaine for the patients undergoing open liver resection with a Mercedes incision. Methods: 126 patients who were scheduled for open liver resection were enrolled in this study. Patients were randomly assigned to receive bilateral ultrasound-guided OSTAPblocks with either 0.375% ropivacaine (groupT) or 0.9% isotonic saline (group C). Both groups also received intravenous patient-controlled analgesia and intravenous 40 mg parecoxib every 12 h for a total of 3 days. Preoperative and intraoperative parameters, plus intraoperative and postoperative cumulative sufentanil consumption, were recorded. Results: 70 patients were enrolled in the study finally. There were no significant differences between the two groups with respect to preoperative parameters, and surgical and anesthetic characteristics. The intraoperative sufentanil use, cumulative sufentanil consumption at 5 min after extubation, 2 h, 4 h,12 h and 24 h after operation in group T was significantly less than that in group C (P = 0.001, 0.001, 0.000, 0.000, 0.001 and 0.044, respectively). Compared with group C, postoperative NRS pain scores at rest were significantly lower at 2 h and 4 h postoperatively in group T (P = 0.04and 0.02, respectively); NRS scores at the time of coughing were also significantly lower in group T than in group C at all time points except 5 min after extubation (all P < 0.001). Furthermore, compared with group C, the number of intraoperative vasodilator use, the extubation time and the incidence of nausea was reduced in group T. Conclusion: Ultrasound-guided OSTAP block with ropivacaine can significantly decrease the perioperative cumulative dosage of analgesics and improve analgesic effect without obvious side effects for the patients who underwent an open liver resection with Mercedes incision when compared tothe ultrasound-guided OSTAP block with saline. Trial registration: The study protocol was registered at http://www.chictr.org.cn (ChiCTR-TRC- 14004827) on February 19, 2014. [ABSTRACT FROM AUTHOR]

Background: Caudal epidural block (CEB) may be beneficial in anorectal surgery because its use may extend postoperative analgesia. This dose-finding study aimed to estimate the minimum effective anesthetic concentrations for 95% patients(MEC95) of 20 ml or 25 ml of ropivacaine in with CEB. Patients and methods: In this double-blind, prospective study, the concentration of ropivacaine administered in 20 ml and 25 ml for ultrasound-guided CEB were determined using the sample up-and-down sequential allocation study design of binary response variables. The first participant was given 0.5% ropivacaine. Depending on whether a block was successful or unsuccessful, the concentration of local anesthesia was decreased or increased by 0.025% in the next patient. Every five minutes for 30 min, the sensory blockade using a pin-prick sensation at S3 dermatome compared to at T6 dermatome were evaluated every 5 min within 30 min. An effective CEB was defined as a a reduction of sensation at S3 dermatome and the existence of flaccid anal sphincter. Anesthesia was considered successful if the surgeon could perform the surgery without additional anesthesia. We determined the MEC50 using the Dixon and Massey up-and-down method and estimated the MEC95 using probit regression. Results: The concentration of ropivacaine administered in 20 ml for CEB ranged from 0.2% to 0.5%. Probit regression with a bias-corrected Morris 95% CI derived by bootstrapping showed an MEC50 and MEC 50 of ropivacaine for anorectal surgical anesthesia were 0.27% (95% CI, 0.24 to 0.31) and 0.36%(95% CI, 0.32 to 0.61). The concentration of ropivacaine administered in 25 ml for CEB ranged from 0.175 to 0.5. Probit regression with a bias-corrected Morris 95% CI derived by bootstrapping showed an MEC50 and MEC95 for CEB were 0.24% (95% CI, 0.19 to 0.27) and 0.32% (95% CI, 0.28 to 0.54). Conclusion: With ultrasound-guided CEB, the MEC95 of 0.36% ropivacaine at 20 ml and 0.32% ropivacaine at 25 ml provide adequate surgical anesthesia/analgesia 95% of patients undergoing anorectoal surgery. Trial registration: Clinicaltrails.gov: Retrospectively registered (ChiCTR2100042954; Registration date:1/2, 2021). [ABSTRACT FROM AUTHOR]

Background: HD-Zips (Homeodomain-Leucine Zippers) are a class of plant-specific transcription factors that play multiple roles in plant growth and development. Although some functions of HD-Zip transcription factor have been reported in several plants, it has not been comprehensively studied in peach, especially during adventitious root formation of peach cuttings. Results: In this study, 23 HD-Zip genes distributed on 6 chromosomes were identified from the peach (Prunus persica) genome, and named PpHDZ01-23 according to their positions on the chromosomes. These 23 PpHDZ transcription factors all contained a homeomorphism box domain and a leucine zipper domain, were divided into 4 subfamilies(I-IV) according to the evolutionary analysis, and their promoters contained many different cis-acting elements. Spatio-temporal expression pattern showed that these genes were expressed in many tissues with different levels, and they had distinct expression pattern during adventitious root formation and development. Conclusion: Our results showed the roles of PpHDZs on root formation, which is helpful to better understand the classification and function of peach HD-Zip genes. [ABSTRACT FROM AUTHOR]

Pathogenic variants in MYO15A are known to cause autosomal recessive nonsyndromic hearing loss (ARNSHL), DFNB3. We have previously reported on one ARNSHL family including two affected siblings and identified MYO15A c.5964+3G > A and c.8375 T > C (p.Val2792Ala) as the possible deafness-causing variants. Eight year follow up identified one new affected individual in this family, who also showed congenital, severe to profound sensorineural hearing loss. By whole exome sequencing, we identified a new splice-site variant c.5531+1G > C (maternal allele), in a compound heterozygote with previously identified missense variant c.8375 T > C (p.Val2792Ala) (paternal allele) in MYO15A as the disease-causing variants. The new affected individual underwent unilateral cochlear implantation at the age of 1 year, and 5 year follow-up showed satisfactory speech and language outcomes. Our results further indicate that MYO15A-associated hearing loss is good candidates for cochlear implantation, which is in accordance with previous report. In light of our findings and review of the literatures, 58 splice-site variants in MYO15A are correlated with a severe deafness phenotype, composed of 46 canonical splice-site variants and 12 non-canonical splice-site variants. [ABSTRACT FROM AUTHOR]

Background: Preoperative absolute lymphocyte count (LC) and fibrinogen (FIB) are useful prognostic indicators in colorectal cancer (CRC). However, the prognostic value of the LC to FIB ratio (LFR) has never been addressed. Methods: A total of 189 nonmetastatic CRC patients after resection were enrolled retrospectively. The significance of the LFR in predicting disease-free survival (DFS) and overall survival (OS) was estimated by receiver operating characteristic curve analysis, and the prognostic efficacy was compared with individual LC and FIB. Patients were assigned to LFR low or high subgroups. Differences in clinicopathological features among these subgroups were calculated, and the survival differences of these subgroups were determined by the Kaplan-Meier analysis. A Cox proportional hazards model was applied to test the risk factors for survival. Results: Taking 0.54 as the optimal cutoff point, the LFR had sensitivities of 79.70% and 86.40% and specificities of 52.30% and 51.00% in predicting the DFS and OS, respectively. A total of 109/189 (57.67%) patients were assigned to the LFR low group, and these patients were more likely to be characterized by criteria such as T3 + T4 (P < 0.01), stage 3 (P < 0.01), tumor deposits (P = 0.01), high CEA (P < 0.01), or CA19-9 levels (P = 0.04). And they also displayed worse DFS (log rank = 18.57, P < 0.01) and OS (log rank = 20.40, P < 0.01) than the high LFR group. Finally, the LFR was independently associated with inferior DFS (HR = 0.32, 95% CI: 0.16–0.61, P < 0.01) and OS (HR = 0.23, 95% CI: 0.09–0.55, P < 0.01). Conclusions: The LFR is a useful prognostic indicator in nonmetastatic CRC, and patients with a relatively low LFR had poor survival. [ABSTRACT FROM AUTHOR]

Background: While optimizing spirometry is a challenge for lung function labs, long-term variability if any between IOS (impulse oscillometry) parameters and spirometry is not clearly known in stable COPD (chronic obstructive pulmonary disease) and chronic asthma. The forced oscillation technique is increasingly employed in routine lung function testing. Our aim in this study was to determine the variability in oscillometric parameters between clinic visits over weeks or months in two patient groups during a period of clinical stability. Moreover, the research assessed relationships between IOS parameters long-term variability and COPD severity.Methods: We used data from 73 patients with stable COPD and 119 patients with stable asthma at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Patients were included if they had three or more clinic visits where spirometry and IOS were performed during a clinically stable period. Data recorded from the first three visits were used. The standard deviation (SDbv), the coefficient of variation (COV), intraclass correlation coefficient (ICC) and the coefficient of repeatability (COR) were calculated, Wilcoxon Mann-Whitney test was used for data that did not conform to normality of distributions, Kruskal Wallis test was used to compare with multiple groups, post hoc comparison was analyzed by Bonferroni, Spearman correlation coefficients for non-parametric data, the multiple regression analyses to determine the relationship between long-term variability and airflow obstruction.Results: (1) The repeatability of IOS resistance parameters with ICC values > 0.8 was high in COPD and asthma. ICC values of IOS resistance parameters were higher than IOS reactance parameters; (2) the repeatability of spirometry parameters with ICC values < 0.8 was lower than IOS resistance parameters in different GOLD (the Global Initiative for Chronic Obstructive Lung Disease) stages, the higher the stage the worse the repeatability; (3) the severity of airflow obstruction was correlated with long-term variability of R5 (R at 5 Hz) (P < 0.05) in GOLD4, not with long-term variability of R20 (R at 20 Hz) (P > 0.05) and R5-R20 (P > 0.05).Conclusion: IOS resistance parameters have good long-term repeatability in asthma and COPD. Additionally, repeatability of spirometry parameters is lower than IOS resistance parameters in different GOLD stages. [ABSTRACT FROM AUTHOR]

Background: Cytoplasmic male sterility (CMS), which naturally exists in higher plants, is a useful mechanism for analyzing nuclear and mitochondrial genome functions and identifying the role of mitochondrial genes in the plant growth and development. Polima (pol) CMS is the most universally valued male sterility type in oil-seed rape. Previous studies have described the pol CMS restorer gene Rfp and the sterility-inducing gene orf224 in oil-seed rape, located in mitochondria. However, the mechanism of fertility restoration and infertility remains unknown. Moreover, it is still unknown how the fecundity restorer gene interferes with the sterility gene, provokes the sterility gene to lose its function, and leads to fertility restoration. Result: In this study, we used multi-omics joint analysis to discover candidate genes that interact with the sterility gene orf224 and the restorer gene Rfp of pol CMS to provide theoretical support for the occurrence and restoration mechanisms of sterility. Via multi-omics analysis, we screened 24 differential genes encoding proteins related to RNA editing, respiratory electron transport chain, anther development, energy transport, tapetum development, and oxidative phosphorylation. Using a yeast two-hybrid assay, we obtained a total of seven Rfp interaction proteins, with orf224 protein covering five interaction proteins. Conclusions: We propose that Rfp and its interacting protein cleave the transcript of atp6/orf224, causing the infertility gene to lose its function and restore fertility. When Rfp is not cleaved, orf224 poisons the tapetum cells and anther development-related proteins, resulting in pol CMS mitochondrial dysfunction and male infertility. The data from the joint analysis of multiple omics provided information on pol CMS's potential molecular mechanism and will help breed B. napus hybrids. [ABSTRACT FROM AUTHOR]

Background: Cystic echinococcosis (CE) is a worldwide parasitic zoonosis caused by infection of the larval stage of tapeworm Echinococcus granulosus. In human CE, the parasites develop and form cysts in internal organs. The differentiated cysts can be classified into five types based on WHO-IWGE standard CE1-5 representing different developmental stages. Infection with E. granulosus triggers hosts’ humoral and cellular response, displaying elevated serum antibodies and Th1 and Th2 cytokines, which are presumed to be in association with the disease outcome. Identification of immunological markers for evaluation of disease progression has been a growing concern. However, the distinctive profile of cytokines and antibodies associated with the cyst progression has not been ascertained. Methods: To better understand the interaction between host immune response and disease outcome, the present study followed-up four CE patients over three years by yearly measuring serum level of 27 cytokines, total IgG and isotypes, and ultrasound scanning, beginning in year 1 for all patients with CE1 and CE2 cysts before treatment and continued in year 2 with CE4 and in year 3 with CE3-CE5 post-treatment. Results: Nine cytokines including Th1-type IL-2, Th17-type IL-17A, and inflammatory cytokines IL-1β, IL-1Rα and TNF-α, chemokines IL-8, MIP-1α, MIP-1β, and growth factor G-CSF were significantly elevated in patients with cyst type CE1, compared to the normal controls, and then declined to a normal level at CE4 and CE5. Examining the antibody production, we found that serum specific IgG was significantly increased in patients with active and transitional cysts, specifically the total IgG at CE1/CE3/CE4-CE5, IgG4 at CE1 and IgG1 at CE1/CE3 cyst status, in comparison with the normal controls, but showed no significant changes between the cyst stages. Conclusions: Our findings provide new information on the profile of multiplex cytokines and serum antibodies associated with cyst stages in cystic echinococcosis patients through a three-year follow-up, implying that further studies using an approach combining cyst-associated immune parameters may aid in identifying immunological markers for differentiation of disease progression. [ABSTRACT FROM AUTHOR]

Background: To retrospectively investigate the clinical characteristics, initial treatment, relapse, therapy outcome, and prognosis of Chinese patients with primary testicular lymphoma (PTL) through analysis of the cases of our institute.Methods: From December 2008 to July 2018, all patients with PTL were included in this study. Kaplan-Meier method was used to estimate PFS and OS. The Cox proportional hazards model was used to compare the survival times for groups of patients differing in terms of clinical and laboratory parameters.Results: All 28 PTL patients (24 DLBCL, three NK/T lymphomas, and one Burkkit's lymphoma) with a median age of 65.5 years were included in this study. Six patients were observed recurrence among all the 22 individuals evaluated. Following orchiectomy and systemic chemotherapy, with or without intrathecal prophylaxis, complete response was achieved in 15 (68%) patients. For DLBCL patients, the median progression-free survival (PFS) was 44.63 months (95% CI 17.71-71.56 months), and the median overall survival (OS) was 77.02 months (95% CI, 57.35-96.69 months). For all the DLBCL patients, the 5-year PFS and 5-year OS were 35.4% (95%CI, 14.8-56.0%) and 53.4% (95%CI, 30.1-76.7%). Without further chemotherapy following orchiectomy (HR = 3.4, P = 0.03) were associated with inferior PFS of DLBCL patients. Advanced Ann Arbor stage (HR =5.9, P = 0.009) and high (international prognostic index, IPI) score: 3-5 (HR =3.9, P = 0.04) were correlated with shorter OS of DLBCL patients.Conclusion: This study confirms that PTL is an aggressive malignant with a poor prognosis. Limited Ann Arbor stage, further chemotherapy following orchiectomy, and low IPI score (less than 2) are correlated with superior survival for DLBCL patients. [ABSTRACT FROM AUTHOR]

Background: Peach (Prunus persica L.) is a diploid species and model plant of the Rosaceae family. In the past decade, significant progress has been made in peach genetic research via DNA markers, but the number of these markers remains limited. Results: In this study, we performed a genome-wide DNA markers detection based on sequencing data of six distantly related peach accessions. A total of 650,693~1,053,547 single nucleotide polymorphisms (SNPs), 114,227~178,968 small insertion/deletions (InDels), 8386~12,298 structure variants (SVs), 2111~2581 copy number variants (CNVs) and 229,357~346,940 simple sequence repeats (SSRs) were detected and annotated. To demonstrate the application of DNA markers, 944 SNPs were filtered for association study of fruit ripening time and 15 highly polymorphic SSRs were selected to analyze the genetic relationship among 221 accessions. Conclusions: The results showed that the use of high-throughput sequencing to develop DNA markers is fast and effective. Comprehensive identification of DNA markers, including SVs and SSRs, would be of benefit to genetic diversity evaluation, genetic mapping, and molecular breeding of peach. [ABSTRACT FROM AUTHOR]

Background: Previous studies have investigated the vitamin D status in patients with chronic hepatitis B virus (HBV) infection and its relationship with HBV replication, the results however were inconsistent. The present meta-analysis was carried out to compare the vitamin D levels between patients with chronic hepatitis B (CHB) and healthy controls, and to determine whether vitamin D levels were correlated with HBV viral loads significantly.Methods: A systematic search was conducted via PubMed, Web of Science, EMBASE and the Cochrane Library to identify eligible studies until September 28, 2017. We calculated pooled mean difference (MD) and 95% confidence intervals (CI) to quantitatively estimate the difference of vitamin D levels between CHB patients and controls. In addition, correlation between serum vitamin D levels and HBV viral loads was defined by summary correlation coefficient (r value) and the corresponding 95% CI.Results: A total of 7 studies involving 814 CHB patients and 696 healthy controls were included. A significantly decreased vitamin D levels was found in CHB patients compared with healthy controls: pooled MD (95% CI) was - 2.03 ng/mL (- 2.60, - 1.46). Latitude-stratified subgroup analysis indicated this difference was more obvious in low latitude areas, with a bigger pooled MD (95% CI) of - 2.72 ng/mL (- 4.57, - 0.87). In addition, we observed an inverse correlation between serum vitamin D levels and HBV viral loads: pooled r (95% CI) was - 0.41(- 0.54, - 0.27).Conclusions: Our results showed that vitamin D levels were lower in CHB patients than that of healthy controls and inversely correlated with HBV viral loads, although future comprehensive studies are needed to clarify the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: HELLP syndrome is a rare disease in China, and 20% of patients with severe preeclampsia have been accompanied with HELLP syndrome, which is characterized by the presence of hemolysis, elevated liver enzymes and low platelet count.Case Presentation: In this case, we reported that a patient with preeclampsia was diagnosed with HELLP syndrome. Furthermore, hepatic infarction also was found via the computed tomographic (CT) images, which showed peripheral wedge-shaped inhomogeneous low attenuation in the right hepatic lobes via plain CT scan, and the low-density shadow and mottled appearance in the same areas where vessels were seen coursing through them via contrast-enhanced CT scan.Conclusions: Besides typical clinical manifestations of the pregnant patient with preeclampsia, the typical laboratory evidences were elevated liver enzymes and thrombocytopenia. The abdominal CT scan showed imaging features of hepatic infarction, which was helpful to identify the rare complication of HELLP syndrome. Thus, we diagnosed a patient with HELLP syndrome with hepatic infarction, though the patient had no chance to do the liver biopsy. [ABSTRACT FROM AUTHOR]

Background The spleen is thought to be central in regulating the immune system, a metabolic asset involved in endocrine function. Overwhelming postsplenectomy infection leads to a mortality rate of up to 50%. However, there is still controversy on performing subtotal splenectomy as treatment of splenomegaly due to portal hypertension in cirrhotic patients. In the present study, immunocytes and the indexes of splenic size, hemodynamics, hematology and immunology in the residual spleen were analyzed to support subtotal splenectomy due to splenomegaly. Results In residual spleen, T lymphocytes mainly were focal aggregation in the periarterial lymphatic sheath. While B lymphocytes densely distributed in splenic corpuscle. In red pulp, macrophages were equally distributed in the splenic cord and adhered to the wall of splenic sinus with high density. The number of unit area T and B lymphocytes of splenic corpuscle and marginal zone as well as macrophages of red pulp were obviously increased in the residual spleen, while the number of macrophages didn't be changed among the three groups in white pulp. While there were some beneficial changes (i.e., Counts of platelet and leucocyte as well as serum proportion of CD3+ T cells, CD4+ T cells, CD8+ T cells were increased markedly; serum levels of M-CSF and GM-CSF were decreased significantly; The proportion of granulocyte, erythrocyte, megakaryocyte in bone marrow were changed obviously; But serum IgA, IgM, IgG, Tuftsin level, there was no significant difference; splenic artery flow volume, portal venous diameter and portal venous flow volume, a significant difference was observed in residual spleen) in the clinical indices. Conclusion After subtotal splenectomy with splenomegaly due to portal hypertension in cirrhotic patients, the number of unit area T and B lymphocytes, and MØ in red pulp of residual spleen increased significantly. However, whether increase of T, B lymphocytes and MØs in residual splenic tissue can enhance the immune function of the spleen, still need further research to confirm. [ABSTRACT FROM AUTHOR]

Background Inherited genetic defects play an important role in congenital hearing loss, contributing to about 60% of deafness occurring in infants. Hereditary nonsyndromic hearing loss is highly heterogeneous, and most patients with a presumed genetic etiology lack a specific molecular diagnosis. Methods By whole exome sequencing, we identified responsible gene of family 4794 with autosomal recessively nonsyndromic hearing loss (ARNSHL). We also used DNA from 56 Chinese familial patients with ARNSHL (autosomal recessive nonsyndromic hearing loss) and 108 ethnicity-matched negative samples to perform extended variants analysis. Results We identified MYO15A c.IVS25 + 3G > A and c.8375 T > C (p.V2792A) as the diseasecausing mutations. Both mutations co-segregated with hearing loss in family 4794, but were absent in the 56 index patients and 108 ethnicity-matched controls. Conclusions Our results demonstrated that the hearing loss of family 4794 was caused by novel compound heterozygous mutations in MYO15A. [ABSTRACT FROM AUTHOR]

Background: Leukocytes play an important role in cancer development. However, the impact of chemotherapyassociated neutropenia/lymphopenia on the prognosis of adjuvant chemotherapy is unknown. Here, we aimed to explore the impact of chemotherapy-associated neutrophil/lymphocyte counts on prognosis of adjuvant chemotherapy in colorectal cancer (CRC) and the risk factors for developing neutropenia/lymphopenia which showed impact on the prognosis of CRC receiving adjuvant chemotherapy. Methods: From February 2003 to January 2011, 243 stage II and III CRC patients receiving adjuvant chemotherapy were enrolled in this retrospective study. The associations between neutrophil/ lymphocyte counts and disease free survival (DFS)/overall survival (OS) of CRC, and the risk factors for neutropenia/lymphopenia were investigated. Results: No association of chemotherapy-associated neutrophil counts and CRC recurrence (AUC = 0.474, P = 0.534), death (AUC = 0.449, P = 0.249) was found by ROC analysis. However, the chemotherapy-associated lymphocyte counts could significantly affect CRC recurrence (AUC = 0.634, P = 0.001), or death(AUC = 0.607, P = 0.015), with a optimized cut-off of 0.66 × 109/L for recurrence, and 0.91 × 109/L for death, respectively. Kaplan-Meier method showed chemotherapy-associated lymphopenia <0.66 × 109/L was associated with shorter DFS (P < 0.0001), and chemotherapy-associated lymphopenia <0.91 × 109/L was associated with shorter OS (P = 0.003). Cox regression model showed chemotherapy-associated lymphopenia <0.66 × 109/L was the independent prognostic factor for DFS (HR, 3.521; 95%CI = 1.703-7.282), and chemotherapy-associated lymphopenia <0.91 × 109/L was the independent prognostic factor for OS (HR, 2.083; 95% CI = 1.103-3.936). Multivariate logistic regression showed the risk of developing chemotherapy-associated lymphopenia <0.66 × 109/L was found in those with pretreatment CEA ⩾10 ng ml-1 (OR, 3.338; 95% CI = 1.523-7.315), and the risk of developing chemotherapy-associated lymphopenia <0.91 × 109/L was found in those with age >60 years (OR, 2.872; 95% CI = 1.344-6.136). Conclusions: Chemotherapy-associated lymphopenia <0.66 × 109/L /0.91 × 109/L has a significant impact on the prognosis of CRC receiving adjuvant chemotherapy. Pretreatment CEA ⩾10 ng ml-1 is the independent risk factor for developing lymphopenia <0.66 × 109/L, and age >60 years is the independent risk factor for developing lymphopenia <0.91 × 109/L during adjuvant chemotherapy of CRC. [ABSTRACT FROM AUTHOR]

Background: The differential diagnosis for hereditary ataxia encompasses a variety of diseases characterized by both autosomal dominant and recessive inheritance. There are no curative treatments available for these neurodegenerative conditions. This open label treatment study used human umbilical cord blood-derived mononuclear cells (CBMC) combined with rehabilitation training as potential disease modulators.Methods: 30 patients suffering from hereditary ataxia were treated with CBMCs administered systemically by intravenous infusion and intrathecally by either cervical or lumbar puncture. Primary endpoint measures were the Berg Balance Scale (BBS), serum markers of immunoglobulin and T-cell subsets, measured at baseline and pre-determined times post-treatment.Results: A reduction of pathological symptoms and signs was shown following treatment. The BBS scores, IgG, IgA, total T cells and CD3+CD4 T cells all improved significantly compared to pre-treatment values (P < 0.01~0.001). There were no adverse events.Conclusion: The combination of CBMC infusion and rehabilitation training may be a safe and effective treatment for ataxia, which dramatically improves patients' functional symptoms. These data support expanded double blind, placebo-controlled studies for these treatment modalities. [ABSTRACT FROM AUTHOR]

Background:

Background: The biological production of 2,3-butanediol from xylose-rich raw materials from Klebsiella pneumoniae is a low-cost process. RpoD, an encoding gene of the sigma factor, is the key element in global transcription machinery engineering and has been successfully used to improve the fermentation with Escherichia coli. However, whether it can regulate the tolerance in K. pneumoniae remains unclear. Results: In this study, the kpC mutant strain was constructed by altering the expression quantity and genotype of the rpoD gene, and this exhibited high xylose tolerance and 2,3-butanediol production. The xylose tolerance of kpC strain was increased from 75 to 125 g/L, and the yield of 2,3-butanediol increased by 228.5% compared with the parent strain kpG, reaching 38.6 g/L at 62 h. The RNA sequencing results showed an upregulated expression level of 500 genes and downregulated expression level of 174 genes in the kpC mutant strain. The pathway analysis further showed that the differentially expressed genes were mainly related to signal transduction, membrane transport, carbohydrate metabolism, and energy metabolism. The nine most-promising genes were selected based on transcriptome sequencing, and were evaluated for their effects on xylose tolerance. The overexpression of the tktA encoding transketolase, pntA encoding NAD(P) transhydrogenase subunit alpha, and nuoF encoding NADH dehydrogenase subunit F conferred increased xylose consumption and increased 2,3-butanediol production to K. pneumoniae. Conclusions: These results suggest that the xylose tolerance and 2,3-butanediol production of K. pneumoniae can be greatly improved by the directed evolution of rpoD. By applying transcriptomic analysis, the upregulation of tktA, pntA, and nuoF that were coded are essential for the xylose consumption and 2,3-butanediol production. This study will provide reference for further research on improving the fermentation abilities by means of other organisms. [ABSTRACT FROM AUTHOR]

Background: Guangxi is the province most seriously affected by rabies virus (RABV) in China. Those most affected by RABV each year are people in rural areas, where dogs are the main cause of human infection with the virus.Methods: In this study, we established a rabies vaccination demonstration program that included eradication, core, and peripheral areas. This program was implemented for 9 years and comprised three stages: 12 counties in the first stage (2008-2010), 21 counties in the second stage (2011-2013), and then extending to all counties of Guangxi Province in the third stage (2014-2016). The program included a dog vaccination campaign, surveillance of clinically healthy dogs who may be potential RABV carriers, monitoring anti-RABV antibody titers in vaccinated dogs, and compiling and reporting statistics of human rabies cases.Results: The target effectiveness was achieved in the eradication, core, and peripheral areas in all three stages. The vaccination demonstration program successfully promoted RABV vaccination of domestic dogs throughout Guangxi Province by drawing upon the experience gained at key points. Compared with a vaccination coverage rate of 39.42-46.85% in Guangxi Province overall during 2003-2007, this rate gradually increased to 48.98-52.67% in 2008-2010, 60.24-69.67% in 2011-2013, and 70.09-71.53% in 2014-2016, thereby meeting World Health Organization requirements. The total cases of human rabies in the province decreased from 602 in 2004 to 41 cases in 2017.Conclusions: The present pilot vaccination program obviously increased the rabies vaccination and seroconversion rates, and effectively reduced the spread of rabies from dogs to humans as well as the number of human rabies cases, thus successfully controlling rabies in Guangxi. [ABSTRACT FROM AUTHOR]

Background: The membrane attack complex (MAC) is a key player in the pathogenesis of age-related macular degeneration (AMD) and is a putative activator of the NLRP3 inflammasome. Amyloid beta (Aβ), a component of drusen deposits, has also been implicated in inflammasome activation by our work and those of others. However, the interactions of MAC and Aβ are still poorly understood, especially their roles in aging and retinal degenerative pathologies. Since inflammasome activation may represent a key cellular pathway underlying age-related chronic inflammation in the eye, the purpose of this study is to identify the effects associated with MAC and inflammasome activation in the retinal pigment epithelium (RPE)/choroid and to evaluate the therapeutic merits of MAC suppression. Methods: Adult Long-Evans rats were divided into treatment and control groups. Treatment groups received oral aurin tricarboxylic acid complex (ATAC), a MAC inhibitor, in drinking-water, and control groups received drinking-water alone (No ATAC). Groups were sacrificed at 7.5 or 11.5 months, after approximately 40 days of ATAC treatment. To study age-related changes of Aβ and MAC in RPE/choroid, naive animals were sacrificed at 2.5, 7.5, and 11.5 months. Eye tissues underwent immunohistochemistry and western blot analysis for MAC, Aβ, NF-κB activation, as well as cleaved caspase-1 and IL-18. Vitreal samples were collected and assessed by multiplex assays for secreted levels of IL-18 and IL-1β. Statistical analyses were performed, and significance level was set at p ≤ 0.05. Results: In vivo studies demonstrated an age-dependent increase in MAC, Aβ, and NF-κB activation in the RPE/choroid. Systemic ATAC resulted in a prominent reduction in MAC formation and a concomitant reduction in inflammasome activation measured by cleaved caspase-1 and secreted levels of IL-18 and IL-1β, but not in NF-κB activation. In vitro studies demonstrated Aβ-induced MAC formation on RPE cells. Conclusions: Age-dependent increases in Aβ and MAC are present in the rodent outer retina. Our results suggest that suppressing MAC formation and subsequent inflammasome activation in the RPE/choroid may reduce chronic low-grade inflammation associated with IL-18 and IL-1β in the outer retina. [ABSTRACT FROM AUTHOR]

Background: Inherited genetic defects play an important role in congenital hearing loss, contributing to about 60% of deafness occurring in infants. Hereditary nonsyndromic hearing loss is highly heterogeneous, and most patients with a presumed genetic etiology lack a specific molecular diagnosis.Methods: By whole exome sequencing, we identified responsible gene of family 4794 with autosomal recessively nonsyndromic hearing loss (ARNSHL). We also used DNA from 56 Chinese familial patients with ARNSHL (autosomal recessive nonsyndromic hearing loss) and 108 ethnicity-matched negative samples to perform extended variants analysis.Results: We identified MYO15A c.IVS25+3G>A and c.8375 T>C (p.V2792A) as the disease-causing mutations. Both mutations co-segregated with hearing loss in family 4794, but were absent in the 56 index patients and 108 ethnicity-matched controls.Conclusions: Our results demonstrated that the hearing loss of family 4794 was caused by novel compound heterozygous mutations in MYO15A. [ABSTRACT FROM AUTHOR]

Background: Cerebral infarction caused by different reasons seems differ in fibrinogen levels, so the current work intends to explore the relationship between the fibrinogen level and subtypes of the TOAST criteria in the acute stage of ischemic stroke.Methods: A total of 577 case research objects were treated acute ischemic stroke patients in our hospital from December 2008 to December 2010, and blood samples within 72 hours of the onset were processed with the fibrinogen (PT-der) measurement. Classification of selected patients according to the TOAST Criteria was conducted to study the distribution of fibrinogen levels in the stroke subtypes.Results: The distribution of fibrinogen levels in the subtypes was observed to be statistically insignificant.Conclusions: In the acute stage of ischemic stroke, fibrinogen level was not related to the subtypes of the TOAST criteria. [ABSTRACT FROM AUTHOR]

Background: Leukocytes play an important role in cancer development. However, the impact of chemotherapy-associated neutropenia/lymphopenia on the prognosis of adjuvant chemotherapy is unknown. Here, we aimed to explore the impact of chemotherapy-associated neutrophil/lymphocyte counts on prognosis of adjuvant chemotherapy in colorectal cancer (CRC) and the risk factors for developing neutropenia/lymphopenia which showed impact on the prognosis of CRC receiving adjuvant chemotherapy.Methods: From February 2003 to January 2011, 243 stage II and III CRC patients receiving adjuvant chemotherapy were enrolled in this retrospective study. The associations between neutrophil/ lymphocyte counts and disease free survival (DFS)/overall survival (OS) of CRC, and the risk factors for neutropenia/lymphopenia were investigated.Results: No association of chemotherapy-associated neutrophil counts and CRC recurrence (AUC = 0.474, P = 0.534), death (AUC = 0.449, P = 0.249) was found by ROC analysis. However, the chemotherapy-associated lymphocyte counts could significantly affect CRC recurrence (AUC = 0.634, P = 0.001), or death(AUC = 0.607, P = 0.015), with a optimized cut-off of 0.66 × 10(9)/L for recurrence, and 0.91 × 10(9)/L for death, respectively. Kaplan-Meier method showed chemotherapy-associated lymphopenia <0.66 × 10(9)/L was associated with shorter DFS (P < 0.0001), and chemotherapy-associated lymphopenia <0.91 × 10(9)/L was associated with shorter OS (P = 0.003). Cox regression model showed chemotherapy-associated lymphopenia <0.66 × 10(9)/L was the independent prognostic factor for DFS (HR, 3.521; 95%CI = 1.703-7.282), and chemotherapy-associated lymphopenia <0.91 × 10(9)/L was the independent prognostic factor for OS (HR, 2.083; 95% CI = 1.103-3.936). Multivariate logistic regression showed the risk of developing chemotherapy-associated lymphopenia <0.66 × 10(9)/L was found in those with pretreatment CEA ≥10 ng ml(-1) (OR, 3.338; 95% CI = 1.523-7.315), and the risk of developing chemotherapy-associated lymphopenia <0.91 × 10(9)/L was found in those with age >60 years (OR, 2.872; 95% CI = 1.344-6.136).Conclusions: Chemotherapy-associated lymphopenia <0.66 × 10(9)/L /0.91 × 10(9)/L has a significant impact on the prognosis of CRC receiving adjuvant chemotherapy. Pretreatment CEA ≥10 ng ml(-1) is the independent risk factor for developing lymphopenia <0.66 × 109/L, and age >60 years is the independent risk factor for developing lymphopenia <0.91 × 10(9)/L during adjuvant chemotherapy of CRC. [ABSTRACT FROM AUTHOR]

Background: Intestinal hyper-permeability plays a critical role in the etiopathogenesis of inflammatory bowel disease (IBD) by affecting the penetration of pathogens, toxic compounds and macromolecules. 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active form of vitamin D, has been shown to be an important regulator of IBD and recent epidemiology suggests that patients with IBD have an impaired vitamin D status. The purpose of this study is to investigate the possible protective effects of 1,25(OH)2D3 on mucosal injury and epithelial barrier disruption on dextran sulfate sodium (DSS)-induced acute colitis model.Methods: We used DSS-induced acute colitis model to investigate the protective effects of 1,25(OH)2D3 on mucosal injury and epithelial barrier integrity. Severity of colitis was evaluated by disease activity index (DAI), body weight (BW) change, colon length, histology, myeloperoxidase (MPO) activity, and proinflammatory cytokine production including tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In vitro the protective role of 1,25(OH)2D3 was assessed by incubating Caco-2 cells with or without DSS and measuring transepithelial electrical resistance (TEER) and fluorescein isothiocyanate dextran (FITC-D). The intestinal permeability was analyzed by FITC-D, bacterial translocation and measurement of lipopolysaccharide (LPS). Ultrastructural features of the colon tissue and Caco-2 cell monolayer were observed by electron microscopy. Expressions of tight junction (TJ) proteins in the colon mucosa and Caco-2 cells were detected by immunohistochemistry, immunofluorescence, Western blot and real-time fluorescent quantitative PCR, respectively.Results: DSS-induced acute colitis model was characterized by a reduced BW, AUC of BW, serum calcium, higher DAI, AUC of DAI, shortened colon length, elevated MPO activity, worsened histologic inflammation, increased mononuclear cell numbers in mesenteric lymph nodes (MLNs) and colonic lamina propria (LP), and enhanced proteins and mRNA levels of TNF-α and IFN-γ. 1,25(OH)2D3 markedly increased expressions of TJ proteins and mRNA and decreased the FITC-D permeability and the level of LPS. Furthermore, 1,25(OH)2D3 abrogated bacterial translocation to MLNs and ameliorated ultrastructural features of the colon epithelium by scanning electron microscopy (SEM). In vitro, 1,25(OH)2D3 increased TEER, TJ proteins and mRNA expressions, decreased the FITC-D permeability, and preserved structural integrity of the TJ in Caco-2 cells.Conclusions: 1,25(OH)2D3 may play a protective role in mucosal barrier homeostasis by maintaining the integrity of junction complexes and in healing capacity of the colon epithelium. 1,25(OH)2D3 may represent an attractive and novel therapeutic agent for the adjuvant therapy of IBD. [ABSTRACT FROM AUTHOR]