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Aurora-B is a kinase that regulates spindle assembly and kinetochore-microtubule (KT-MT) attachment during mitosis and meiosis. SUMOylation is involved in the oocyte meiosis regulation through promoting spindle assembly and chromosome segregation, but its substrates to support this function is still unknown. It is reported that Aurora-B is SUMOylated in somatic cells, and SUMOylated Aurora-B contributes the process of mitosis. However, whether Aurora-B is SUMOylated in oocytes and how SUMOylation of Aurora-B impacts its function in oocyte meiosis remain poorly understood. In this study, we report that Aurora-B is modified by SUMOylation in mouse oocytes. The results show that Aurora-B colocalized and interacted with SUMO-2/3 in mouse oocytes, confirming that Aurora-B is modified by SUMO-2/3 in this system. Compared with that in young mice, the protein expression of SUMO-2/3 decreased in the oocytes of aged mice, indicating that SUMOylation might be related to mouse aging. Overexpression of Aurora-B SUMOylation site mutants, Aurora-B K207R and Aurora-B K292R , inhibited Aurora-B recruitment and first polar body extrusion, disrupting localization of gamma tubulin, spindle formation and chromosome alignment in oocytes. The results show that it was related to decreased recruitment of p-HDAC6 which induces the high stability of whole spindle microtubules including the microtubules of both correct and wrong KT-MT attachments though increased acetylation of microtubules. Therefore, our results corroborate the notion that Aurora-B activity is regulated by SUMO-2/3 in oocytes, and that SUMOylated Aurora B plays an important role in spindle formation and chromosome alignment., (© 2024. The Author(s).)

Objectives: This study was designed to determine the incidence, contributing factors, and prognostic implications of acute kidney injury (AKI) recovery patterns in patients who experienced AKI after valve replacement surgery (VRS)., Design: A retrospective cohort study was conducted., Setting: The work took place in a postoperative care center in a single large-volume cardiovascular center., Participants: Patients undergoing VRS between January 2010 and December 2019 were enrolled., Intervention: Patients were categorized into three groups based on their postoperative AKI status: non-AKI, AKI with early recovery (less than 48 hours), and persistent AKI., Measurement and Main Results: The primary outcome was in-hospital major adverse clinical events. The secondary outcomes included in-hospital and 1-year mortality. A total of 4,161 patients who developed AKI following VRS were included. Of these, 1,513 (36.4%) did not develop postoperative AKI, 1,875 (45.1%) experienced AKI with early recovery, and 773 (18.6%) had persistent AKI. Advanced age, diabetes, New York Heart Association III-IV heart failure, moderate-to-severe renal dysfunction, anemia, and AKI stages 2 and 3 were identified as independent risk factors for persistent AKI. In-hospital major adverse clinical events occurred in 59 (3.9%) patients without AKI, 88 (4.7%) with early AKI recovery, and 159 (20.6%) with persistent AKI (p < 0.001). Persistent AKI was independently associated with an increased risk of in-hospital adverse events and 1-year mortality. In contrast, AKI with early recovery did not pose additional risk compared with non-AKI patients., Conclusions: In patients who develop AKI following VRS, early AKI recovery does not pose additional risk compared with non-AKI. However, AKI lasting more than 48 hours is associated with an increased risk of in-hospital and long-term adverse outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Chronic refractory wounds were common and the treatments were complicated for burn and plastic surgeons. This study was to investigate the bacterial distribution characteristics and bacterial drug resistance of chronic refractory wound secretions., Methods: The authors retrospectively analyzed 425 patients with chronic refractory wound infection. The results of bacterial culture of wound secretions and drug sensitivity test were retrospectively analyzed. Further, the location area of the wound was divided into 4 regions, and the difference of the bacterial culture results between different regions was analyzed., Results: The wound secretions were cultured into 401 bacterial strains, including 206 gram-positive bacteria strains, accounting for 51.4%, with the highest detection rate of Staphylococcus aureus at 26.2% (105/401). There were 195 gram-negative bacteria strains, accounting for 48.6%, with the highest detection rate of Pseudomonas aeruginosa at 14.2% (57/401). There were 6 fungal strains. The proportion of gram-negative bacteria in the III region of the wound zone was significantly greater than that in the other 3 regions., Conclusions: The detection rate of gram-positive bacteria and gram-negative bacteria of chronic refractory wound secretions is not much different. However, in the area close to the perineum (III region), gram-negative bacteria is significantly higher, which has a certain reference value for the use of antibiotics in clinical practice., Level of Evidence: Level 4., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Objectives: Nivalenol (NIV) is a secondary metabolite of type B trichothecene mycotoxin produced by Fusarium genera, which is widely found in contaminated food and crops such as corn, wheat and peanuts. NIV is reported to have hepatotoxicity, immunotoxicity, genotoxicity, and reproductive toxicity. Previous studies indicate that NIV disturbs mammalian oocyte maturation. Here, we reported that delayed cell cycle progression might be the reason for oocyte maturation defect caused by NIV exposure., Methods and Results: We set up a NIV exposure model and showed that NIV did not affect G2/M transition for meiosis resumption, but disrupted the polar body extrusion of oocytes. Further analysis revealed that oocytes were arrested at metaphase I, which might be due to the lower expression of Cyclin B1 after NIV exposure. After cold treatment, the microtubules were disassembled in the NIV-exposed oocytes, indicating that NIV disrupted microtubule stability. Moreover, NIV affected the attachment between kinetochore and microtubules, which further induced the activation of MAD2/BUBR1 at the kinetochores, suggesting that spindle assemble checkpoint (SAC) was continuously activated during oocyte meiotic maturation., Conclusions: Taken together, our study demonstrated that exposure to NIV affected Cyclin B1 expression and activated microtubule stability-dependent SAC to ultimately disturb cell cycle progression in mouse oocyte meiosis., (© 2022 The Authors. Cell Proliferation published by European Cell Proliferation Society and John Wiley & Sons Ltd.)

Background: Colorectal cancer (CRC) is a major health concern globally, but exhibits regional and/or environmental distinctions in terms of outcome especially for patients with stage III CRC., Methods: From 2014 to 2016, matched pairs of tumor and adjacent normal tissue samples from 60 patients with stage I-IV CRC from Chang Gung Memorial Hospital in Taiwan were analyzed using next-generation sequencing. The DNA, mRNA, and miRNA sequences of paired tumor tissues were profiled. An observational study with survival analysis was done. Online datasets of The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) were also integrated and compared., Results: The gene that exhibited the highest mutation rate was adenomatous polyposis coli (APC) (75.0%), followed by TP53 (70.0%), KRAS (56.6%), and TTN (48.3%). APC was also the most frequently mutated gene in TCGA and ICGC datasets. Surprisingly, for non-metastatic cases (stages I-III), CRC patients with mutated APC had better outcome in terms of overall survival (p = 0.041) and recurrence free survival (p = 0.0048). Particularly for stage III CRC, the overall survival rate was 94.4% and 67.7%, respectively (p = 0.018), and the recurrence free survival rate was 94.4% and 16.7%, respectively (p = 0.00044). Further clinical and gene expression analyses revealed that the APC wt specimens to a greater extent exhibit poor differentiation state as well as EGFR upregulation, providing molecular basis for the poor prognosis of these patients. Finally, based on integrated transcriptome analysis, we constructed the mRNA-miRNA networks underlying disease recurrence of the stage III CRC and uncovered potential therapeutic targets for this clinical condition., Conclusion: For stage III CRC, patients with mutated APC had better overall and recurrence free survival., Competing Interests: Conflicts of interest The authors disclose no potential conflicts of interest., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Podophyllotoxin (POD) is one of the most characterized lignans that is commonly found in podophyllum, and its preparations and derivatives are widely used in clinical treatment due to strong antitumor and antivirus activities. POD has been reported for its neurotoxicity, liver toxicity, and potential reproductive toxicity. In the present study, we investigated the effects of POD on the organelles of mouse oocytes during meiosis. Our results showed that exposure to POD significantly reduced the developmental competence of mouse oocytes. Further analysis revealed that the endoplasmic reticulum (ER) failed to accumulate to the spindle periphery, suggesting that POD exposure might affect protein synthesis during oocyte meiotic maturation. Similarly, abnormal Golgi apparatus distribution was found after POD exposure, which could be confirmed by the aberrant localization of Rab11a-related vesicles, indicating that POD induced vesicle-based protein transport disorder. We also found the aberrant accumulation of lysosomes in the cytoplasm of POD-exposed oocytes, which implied that POD might lead to aberrant protein degradation. Moreover, the perinuclear distribution of mitochondria was also significantly disturbed, indicating the mitochondrial dysfunction after POD exposure. In all, our study illustrated that exposure to POD might disrupt protein synthesis, transport, degradation, and ATP production by its effects on the distribution and functions of organelles during mouse oocyte meiotic maturation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lu, Xie, Kong, Xu and Sun.)

Streptococcus parasanguinis is a primary colonizer of dental plaque and an opportunistic pathogen for subacute endocarditis. A putative fibronectin binding protein (Spaf&#95;1409) that lacks both an N-terminal signal peptide and a C-terminal cell wall-anchoring motif was identified from the S. parasanguinis FW213 genome. Spaf&#95;1409 was abundantly present in the cytoplasm and also was found in the cell wall preparation and culture supernatant. By using an isogenic mutant strain, MPH4, Spaf&#95;1409 was found to mediate the binding of S. parasanguinis FW213 to fibronectin. Inactivation of Spaf&#95;1409 did not significantly alter the mass of static biofilm, but reduced the resistance of S. parasanguinis against the shearing force in a flow cell biofilm system, resulting in scattered biofilm. The mortality in Galleria mellonella larvae infected with MPH4 was higher than in those infected with wild-type S. parasanguinis. However, fewer viable bacterial cells were recovered from larvae infected with MPH4, compared to those infected with wild-type S. parasanguinis, up to 42 h post infection, suggesting that the infection by MPH4, but not the growth, was responsible for the elevated mortality. The phagocytic analysis using flow cytometry indicated that Spaf&#95;1409 participates in the recognition of S. parasanguinis FW213 by RAW264.7 macrophages, suggesting that inactivation of Spaf&#95;1409 intensified the immune responses in larvae, leading to larval death. Taken together, the data indicate that Spaf&#95;1409 plays different roles in the development of dental biofilm and in systemic infections.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While both genetic and environmental factors have been linked to the incidence and mortality associated with CRC, an ethnic aspect of its etiology has also emerged. Since previous large-scale cancer genomics studies are mostly based on samples of European ancestry, the patterns of clinical events and associated mechanisms in other minority ethnic patients suffering from CRC are largely unexplored. We collected 104 paired and adjacent normal tissue and CRC tumor samples from Taiwanese patients and employed an integrated approach - paired expression profiles of mRNAs and microRNAs (miRNAs) combined with transcriptome-wide network analyses - to catalog the molecular signatures of this regional cohort. On the basis of this dataset, which is the largest ever reported for this type of systems analysis, we made the following key discoveries: (1) In comparison to the The Cancer Genome Atlas (TCGA) data, the Taiwanese CRC tumors show similar perturbations in expressed genes but a distinct enrichment in metastasis-associated pathways. (2) Recurrent as well as novel CRC-associated gene fusions were identified based on the sequencing data. (3) Cancer subtype classification using existing tools reveals a comparable distribution of tumor subtypes between Taiwanese cohort and TCGA datasets; however, this similarity in molecular attributes did not translate into the predicted subtype-related clinical outcomes (i.e., death event). (4) To further elucidate the molecular basis of CRC prognosis, we developed a new stratification strategy based on miRNA-mRNA-associated subtyping (MMAS) and consequently showed that repressed WNT signaling activity is associated with poor prognosis in Taiwanese CRC. In summary, our findings of distinct, hitherto unreported biosignatures underscore the heterogeneity of CRC tumorigenesis, support our hypothesis of an ethnic basis of disease, and provide prospects for translational medicine.

Iophendylate is an oil-based contrast agent used in conventional myelography before the 1980s. We report an unusual case of an 82-year-old woman with iophendylate migration into the intracranial cerebrospinal fluid space after myelography 40 years ago. The patient was treated conservatively and followed up regularly.

Objective: To observe the effect of acupuncture on inflammatory indices and symptoms in patients with acute pelvic inflammatory disease, and investigate its mechanism., Methods: Seventy-nine patients with acute pelvic inflammatory disease were randomly assigned to a control group ( n ＝37) given conventional treatment and an observation group ( n ＝42) given conventional treatment and acupuncture therapy. In the observation group, acupionts of Zhongji(CV 3), Guanyuan(CV 4), Zigong(EX-CA 1), Zusanli(ST 36), Sanyinjiao(SP 6), etc. were selected. Each group received treatment once daily, for a total of 7 days. Tumor necrosis factor (TNF)-α， interleukin (IL)-10 and C-reactive protein (CRP) in the serum, white blood cell (WBC) and neutrophil counts, size of pelvic mass and depth of pelvic effusion, and clinical symptoms were assayed pretreatment and on days 3 and 7., Results: WBC and neutrophils were significantly decreased after treatment in both groups ( P <0.05), and more in the observation group than in the control group ( P <0.05). After treatment, the size of pelvic mass and depth of effusion were less in both groups ( P <0.05), and the efficacy in the observation group was superior to that in the control group ( P <0.05). In the observation group, serum TNF-α， and CRP on day 3 and day 7 were significantly lower than those before treatment ( P <0.05). Se-rum TNF-α and CRP were significantly down-regulated in the observation group compared with those in the control group on both day 3 and day 7 ( P <0.05). In the observation group, serum IL-10 was higher on both day 3 and day 7 than that before treatment ( P <0.05), and was statistically different from that in the control group on both days ( P <0.05). The clinical efficacy in the observation group was superior to that in the control group (95.24% vs 81.08%, P <0.05)., Conclusion: Acupuncture can regulate the levels of inflammatory markers in patients with acute pelvic inflammatory disease, and improve clinical symptoms.

Background: Curcuminoid from Curcuma longa Linnaeus has been demonstrated to be effective in anti-cancer and anti-inflammation. The objectives of the present study were to prepare curcuminoid dispersion and nanoemulsion from C. longa and determine their oral bioavailabilities in rats., Results: After curcuminoid extraction using 99.5% ethanol, bisdemethoxycurcumin (BDMC), demethoxycurcumin (DMC) and curcumin were separated within 10 min by high-performance liquid chromatography using an Eclipse XDB-C18 column (Agilent, Palo Alto, CA, USA) and a gradient mobile phase of 0.1% aqueous formic acid and acetonitrile, with a flow rate of 1 mL min -1 , column temperature of 35 °C and detection wavelength of 425 nm. Curcuminoid nanoemulsion at a particle size of 12.1 nm and encapsulation efficiency 98.8% was prepared using lecithin, Tween 80 and water. A pharmacokinetic study in rats revealed that the parameters including T max , C max , t 1/2 and the area under the curve were higher for curcuminoid nanoemulsions than for curcuminoid dispersion at the same dose employed for gavage administration, whereas, for intravenous injection, an opposite trend was shown. The oral bioavailabilities of BDMC, DMC, curcumin and total curcuminoids in nanoemulsion and dispersion were 34.39 and 4.65%, 39.93 and 5.49%, 47.82 and 9.38%, and 46 and 8.7%, respectively., Conclusion: The results of the present study demonstrate a higher oral bioavailability after incorporation of curcuminoid into nanoemulsion, facilitating its application as a botanic drug. © 2017 Society of Chemical Industry., (© 2017 Society of Chemical Industry.)

Objective: To investigate the immunity to mumps after administrating measles-mumps-rubella vaccine (MMR) among children aged 2-7 years old in Jiangsu province in 2015. Methods: A total of 4 190 healthy children aged 2-7 years old, living in local places for at least 3 months, and having been vaccinated at least 1 dose MMR were recruited to the study from Wujin district of Changzhou city, Gaogang district of Taizhou city and Ganyu district of Lianyungang city by using stratified cluster random sampling method between September and November, 2015. Those who did not accept MMR vaccination, who refused venous blood collection, who had affected mumps according to the memory of parents or teachers and who were diagnosed serious disease by clinical doctors were excluded from study. The self-designed questionnaire was used to collect the general information of the subjects and their MMR immunization history; and 0.5-2.0 ml of venous blood was collected from each subject. ELISA was used to detect the mumps antibody level in the serum of patients. Positive was defined as the antibody level ≥108 mU/ml, and negative as <108 mU/ml. χ(2) test was used to compare the difference in positive rates among subjects; and analysis of variance was used to compare the GMC changes in different time points after MMR vaccination. Results: Among 4 190 children, 2 280 were males (54.42%) and 1 910 were females(45.58%), and the positive rate of IgG antibody was 81.38% (3 344). There were 3 156 (95.18%) children vaccinated with one dose MMR, 187 (4.80%) children with two dose MMR, and 1 (0.02%) child with three dose MMR. The difference in positive rate of IgG antibody among different aged subjects showed statistical significance (χ(2)=58.61, P< 0.001), the highest positive rate was in group of subjects aged 4-5 years old, at 89.43% (406/454), while the lowest positive rate was found among subjects aged 6-7 years old, at 75.63% (1 648/2 179). The positive rate after one dose of MMR vaccination was 79.14% (3 156/3 988), significantly less than it after two doses (93.03%, 187/201) (χ(2)=22.93, P< 0.001). The GMC level at years<1, 1-<2, 2-<3, 3-<4, ≥4 following one dose MMR in the 3 988 children was 152.47, 227.78, 167.08, 126.91, 79.43 mU/ml, whose difference was statistically significant ( F= 51.29, P< 0.001). Conclusion: The sero-prevalence of IgG antibody in the children aged 2-7 years old in Jiangsu province was high. The positive rate among who received two doses MMR was significantly higher than it among who received just one dose, and the GMC level waned with times.

Purpose  In periventricular leukomalacia (PVL), apparent diffusion coefficient (ADC) reduction, normally shown as dark stripe in the peritrigonal (PT) white matter, may be incomplete. We assessed the PT dark stripe to differentiate between PVL patients and control subjects. Patients and Methods  We reviewed the magnetic resonance studies of 27 neonates and young children with PVL and 67 control subjects to assess the PT dark stripe on ADC maps. In PVL patients, the assessment was referred to the location of PVL lesion on fluid-attenuated inversion recovery (FLAIR) imaging. In the controls, the PT region or the location corresponding to FLAIR hyperintensity was evaluated for the dark stripe. We compared the prevalence of the dark stripe on ADC map and the PT FLAIR hyperintensity between the PVL and the control subjects. Results  On ADC map, complete PT dark stripe was present in 67 (100%) of 67 controls but only in 4 (14.8%) of 27 PVL patients ( p -value < 0.01), with sensitivity of 0.85, specificity of 1.0, and accuracy of 0.96. PT FLAIR hyperintensity was present in 44 (65.7%) of 67 controls and in 18 (66.7%) of 27 PVL patients ( p  = 0.920). Conclusion  PVL patients can be differentiated from the control subjects with PT dark stripe on ADC map., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To conduct a meta-analysis to determine whether progesterone, compared with placebo or no treatment, influences mortality and neurologic outcome in traumatic brain injury (TBI)., Methods: To identify eligible studies, systematic searches for randomized controlled trials of progesterone treatment in TBI were conducted in PubMed, Web of Science, EMBASE, Cochrane Library, and ClinicalTrials.gov databases. The search yielded 8 studies that were included in the meta-analysis. Included data were study characteristics, patient demographics, baseline characteristics, progesterone treatment protocol, main outcome of mortality, and secondary neurologic outcome evaluated using the Glasgow Outcome Scale., Results: The 8 studies comprised 2585 patients. The meta-analysis indicated that there was no evidence that progesterone treatment decreased the risk of mortality in patients with TBI; the overall risk ratio was 0.852 (95% confidence interval, 0.632-1.144; P = 0.284). In the secondary outcome analysis, progesterone had no neuroprotective role in improving neurologic outcome; the overall risk ratio was 1.151 (95% confidence interval, 0.0991-1.338; P = 0.06). Subgroup analysis according to the degree of injury assessed by the Glasgow Coma Scale demonstrated similar results., Conclusions: This study is the largest meta-analysis conducted to date to determine whether progesterone is effective in the treatment of TBI. The findings indicate that progesterone treatment does not decrease mortality or improve neurologic outcome in patients with TBI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Nucleolin (NCL) participates in DNA transcription, ribosomal biogenesis and the regulation of RNA stability. However, the contribution of NCL to tumor development is still not clear. Herein, we found that NCL expression correlated with poor prognosis in lung cancer patients. Overexpressed NCL was predominantly cleaved to C-terminal truncated NCL (TNCL). In lung cancer formation, activation of the epidermal growth factor receptor pathway induced NCL expression, and also the expression of matrix metalloproteinase (MMP) 7, which then cleaved NCL at Asp255 to generate TNCL of 55 kDa. TNCL increased the expression of several oncogenes, including MMP9, anaplastic lymphoma kinase (ALK), HIF1a and CBLB, and decreased the expression of tumor suppressors including BRD4, PCM1, TFG and KLF6 by modulating mRNA stability through binding to the 3'-untranslated regions of their transcripts, thus ultimately enhancing metastasis activity. In conclusion, this study identified a novel role of the cleavage form of NCL generated by MMP7 in stabilizing MMP9 mRNA. We also provide a new insight that MMP7 not only cleaves the extracellular matrix to promote tumor invasion but also cleaves NCL, which augment oncogenesis. Blocking NCL cleavage may provide a useful new strategy for lung cancer therapy.

Objective: To observe the difference in the efficacy on traumatic nerve injury among electroacupuncture, warm needling therapy and electroacupuncture plus warm needling therapy and explore the better therapeutic method., Methods: The electromyography (EMG) and electroneurography (ENG) of 93 cases showed traumatic nerve injury of moderate damage. According to the single blind randomization principle, they were divided into an electroacupuncture (EA) group, a warm needling therapy (WN) group and an EA plus WN group, 31 cases in each one. The main acupoints were selected from Yangming Meridian and Shaoyang Meridian corresponding to the distribution of damaged nerves. EA, WN and EA plus WN were applied separately. The treatment was given once every day, 15 treatments made one session. After 3 sessions of treatment (45 treatments in total), EMG and ENG were re-checked and the results were analyzed statistically., Results: Regarding the total effective rate and effective rate, it was 96. 8% (30/31) in the EA plus WN group, which was better than 74.2% (23/31) in the EA group and 77. 4% (24/31) in the WN group (P<0. 05). Concerning to the improvements of EMG, the result in the EA plus WN group was 96.8% (30/31), which was better than the other two groups [74. 2%(23/31),74. 2%(23/31)] (P<0. 05). In terms of the recovery of nerve conduction and amplitude, the results in EA plus WN group [(50.9+/-4. 6)m/s,(8. 8+/-2. 9),microVx1 000] were better than the other two groups [(43.7+/-3.1)m/s,(4. 2+/-1. 9)microV X 1 000,(43. 8+/-3. 3)m/s,(4. 5+/-2. 2)microV X 1 000] (P<0. 05)., Conclusion: EA combined with WN is a better therapy of acupuncture and moxibustion in the treatment of traumatic nerve injury.

Background: Sudden internal carotid artery (ICA) occlusive vasospasm is a serious complication of intracranial aneurysm embolization. Conventional spasmolysis with papaverine yields a generally poor outcome. We believe that arterial infusion of lidocaine may offer a better outcome., Materials and Methods: We retrospectively reviewed the outcome of patients treated with either papaverine or lidocaine infusion for vasospasm during embolization., Results: 14 patients undergoing intracranial aneurysm embolization had a ICA occlusive vasospasm. Among the 8 patients who received conventional treatment with papaverine the vasospasm improved partially in 5. In 3 cases, treatment was ineffective. 6 of the patients died within 3 days. 2 patients developed hemispheric infarction and underwent a decompressive craniectomy and subtotal resection of the infarct; 1 of these 2 patients died after 4 months and the other was severely disabled. In the 6 patients treated with lidocaine, spasmolysis and subsequent aneurysm treatment was successful in 5. In 1 patient who had preoperative stenosis of the carotid artery proximal to the aneurysm spasmolysis failed., Conclusions: ICA occlusive spasm is an extremely serious and often lethal complication in embolization of intracranial aneurysms. Conventional treatment with papaverine has a poor outcome, whereas arterial infusion of lidocaine may achieve better results., (© 2012 by Thieme Medical Publishers, Inc.)

Objective: Temozolomide (TMZ) is an oral alkylating agent widely used in the treatment of refractory glioma. Its efficacy is limited, however, by poor cancer cell penetration and drug resistance. The present study, therefore, aimed to investigate whether hyperbaric oxygen (HBO) may facilitate drug delivery and enhance the anticancer effect of TMZ., Methods: Cultured glioma U251 cells were treated with HBO, TMZ, or TMZ + HBO, or were untreated (controls). Rates of growth inhibition, cell death and apoptosis were investigated using the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, propidium iodide staining and flow cytometry, respectively. Protein levels of vascular endothelial growth factor (VEGF) and multidrug resistance-associated protein-1 (MRP-1) were evaluated by enzyme-linked immunosorbent assay., Results: Compared with TMZ or HBO alone, combined treatment with both therapies synergistically inhibited growth and induced apoptosis and death of cultured glioma U251 cells, which was accompanied by a significant decrease in levels of VEGF and MRP-1., Conclusions: TMZ and HBO synergistically induced the apoptosis of glioma cells, possibly through reduced vascularization and inhibition of drug resistance. The combination of TMZ and HBO may be a powerful treatment for malignant glioma.

Aim: To investigate the effect of Ad-ING4 on proliferation and migration of glioma cells and explore its probable mechanism., Methods: U251 were infected with Ad-ING4. ING4 gene expression was evaluated by RT-PCR. MTT assay was adopted to evaluate the effect of ING4 on proliferation of U251; Boyden chamber assay was used to check the effect of ING4 on the migration of U251. In ING4 transfected U251, Western blot was used for detecting NGF and TrkA expression; Pull-down assay was used for detecting active RhoA expression., Results: ING4 was overexpressed in Ad-ING4 transfected U251 cells. ING4 inhibited proliferation and migration of U251 significantly. Moreover, overexpression of ING4 result in depression of NGF, TrkA and active RhoA., Conclusion: ING4 mediated inhibition of the proliferation and migration of human glioma cells by down regulating NGF, TrkA and active RhoA expression.

Background: Recent studies have discovered that nuclear translocation of nerve growth factor (NGF) and its receptor fragments function differently from the traditional model. This study aimed to uncover the nuclear expression of NGF in astrocytoma and its biological significance., Methods: Ninety-four paraffin-embedded astrocytoma specimens were subjected to immunohistochemical (IHC) and hemotoxylin & eosin (HE) staining. Preoperative cerebrospinal fluid (CSF) specimens and intraoperative snap-frozen astrocytoma tissues were assayed for NGF expression by ELISA and Western blotting. The outcome of patients who contributed samples was tracked. Each ten tissue samples from patients with traumatic brain injury who had received decompression surgery and CSF samples from patients undergoing spinal anesthesia but with no history of nervous system disease were taken as control., Results: NGF-positive immunoreactive products were distributed in both the cytoplasm and nucleus of astrocytoma, but were only located in the cytoplasm of traumatic brain injury (TBI) tissue. NGF nuclear-positive rate (NPR) of grades III - IV astrocytomas (70.0%) was higher than that of grades I - II astrocytoma (28.6%, P < 0.05). NGF-NP expression positively correlated with the NGF concentration in cerebrospinal fluid (CSF) (r = 0.755, P < 0.01). Kaplan-Meier survival analysis indicated that the median survival time was 25 months for NGF-NP astrocytoma grade I - II patients and 42 months in NGF nuclear negative (NGF-NN) astrocytoma grade I - II patients (P < 0.05). In astrocytoma III - IV patients, the median survival was 7 months for NGF-NP patients and 24 months for NGF-NN patients (P < 0.01). Two types of NGF with molecular weights of 13 and 36 kDa were present in astrocytoma, but only the 36 kDa NGF was found in the CSF. NGF expression elevated as the malignancy increased., Conclusions: NGF-NP expression and NGF level in CSF were significant prognostic factors in astrocytoma patients. Because of the easy access of CSF, it may be developed as an index for early diagnosis and surveillance of astrocytoma.

Lychee (Litchi chinensis Sonn.) flower is a major nectar source in Taiwan. Antioxidant activities of acetone, ethanol, and hot-water extracts of the flower were estimated through three biochemical models: inhibition of Cu(2+) -induced oxidation of human low-density lipoprotein, scavenging ability of oxygen radicals in human blood, and inhibition of human erythrocyte hemolysis induced by peroxyl radicals. Composition and content of flavonoids and phenolic acids in these extracts were also determined by high-performance liquid chromatography. Results showed that antioxidant effects of all test models as well as contents of flavonoids and phenolic acids for the lychee flower extracts were in the order: acetone extract > ethanol extract > hot-water extract. Gentistic acid and epicatechin were the major phenolic acid and flavonoid in the extracts, respectively., (© 2011 Institute of Food Technologists®)

Objective: To determine the expression of human papillomavirus (HPV) type 16 E6 oncoprotein in cervical specimens of women with and without cervical intraepithelial neoplasia (CIN)., Materials and Methods: Cervical specimens from 2,530 unscreened women aged 30 to 54 years from Shanxi, China, were obtained. All women were assessed by liquid-based cytology, high-risk HPV DNA tests, and colposcopy with directed biopsy and endocervical curettage as necessary. Women with abnormal cytologic results or positive HPV DNA results were recalled for colposcopy, 4-quadrant cervical biopsies, and endocervical curettage. Women with biopsy-proven CIN and cancer and a convenience sample of HC2-positive, disease-negative women were tested for the presence of HPV-16 infection via HPV-16 E6 DNA-specific polymerase chain reaction. A PDZ interaction-mediated E6 oncoprotein precipitation method followed by E6-specific Western blot was performed on specimens from women with HPV-16 infections. Associations between elevated expression of E6 oncoprotein and CIN 2 and 3 were determined using logistic regression and a reference category of CIN 1 and disease-negative., Results: A significant trend for the detection of HPV-16 E6 oncoprotein in specimen of women with proven HPV-16 infection was determined: 0% (0/12), 12.5% (1/8), 36.4% (4/11), and 42.9% (3/7) of those with negative findings, CIN 1, 2, and 3, respectively (p = .01). Compared with the category combining negative findings and CIN 1, detection of E6 oncoprotein was associated with CIN 2 (odds ratio = 10.9, p = .05) and CIN 3 (odds ratio = 14.3, p = .04)., Conclusions: There is a significant association between elevated expression of E6 oncoprotein and grade of CIN. This finding seems consistent with the role played by E6 oncoprotein in carcinogenesis.

In a feasibility study using a prototype, lateral-flow test for human papillomavirus type 16, 18, and/or 45 (HPV16/18/45) E6 oncoproteins, 51 of 75 (68%; 95% confidence interval [95% CI] of 56 to 78%) of HPV16/18/45 DNA-positive specimens from women with a diagnosis of CIN3+ (cervical intraepithelial neoplasia grade 3+ or cervical cancer) tested positive for HPV16/18/45 E6 oncoprotein. None of 16 (95% CI of 0 to 37%) HPV16/18/45 DNA-positive cervical specimens from women with a negative or CIN1 diagnosis tested positive for HPV16/18/45 E6 oncoprotein.

Background: Resurgence or outbreak of measles recently occurred in both developed and developing countries despite long-standing widespread use of measles vaccine. Measles incidence in China has increased since 2002, particularly in infants and in persons >or= 15 years of age. It is speculated that infants may acquire fewer measles IgG from their mothers, resulting in the reduced duration of protection during their early months of life. This study aimed to clarify the reason of increased susceptibility to measles in young infants in China. Measles IgG in 24 measles infants

Cell alignment plays an important role in the repair of damaged peripheral nerves. The aligned Schwann cells could direct the axonal outgrowth during nerve reconstruction. One way of aligning Schwann cells is to use surface grooves in micrometric dimensions. In this study, microgrooves on chitosan or poly(D,L-lactide) (PLA) were fabricated and the behaviors of Schwann cells and glial cell line C6 on these surfaces were examined. It was found that Schwann cells and C6 cells could be successfully aligned by the microgrooves, and express the genes related to the production of neurotrophic factors. The polymer conduits with microgrooves on the inner surface were implanted in rats to repair the damaged sciatic nerve. The microgrooved conduits were demonstrated to enhance peripheral nerve regeneration as compared to the smooth conduits.

In neuronal synapses, PDZ domains [postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1] of PSD-95 proteins interact with C termini of NMDA receptor [NMDAR (NR)] subunits, linking them to downstream neurotoxic signaling molecules. Perturbing NMDAR/PSD-95 interactions with a Tat peptide comprising the nine C-terminal residues of the NR2B subunit (Tat-NR2B9c) reduces neurons' vulnerability to excitotoxicity and ischemia. However, NR subunit C termini may bind many of >240 cellular PDZs, any of which could mediate neurotoxic signaling independently of PSD-95. Here, we performed a proteomic and biochemical analysis of the interactions of all known human PDZs with synaptic signaling proteins including NR1, NR2A-NR2D, and neuronal nitric oxide synthase (nNOS). Tat-NR2B9c, whose interactions define PDZs involved in neurotoxic signaling, was also used. NR2A-NR2D subunits and Tat-NR2B9c had similar, highly specific, PDZ protein interactions, of which the strongest were with the PSD-95 family members (PSD-95, PSD-93, SAP97, and SAP102) and Tax interaction protein 1 (TIP1). The PSD-95 PDZ2 domain bound NR2A-NR2C subunits most strongly (EC50, approximately 1 microM), and fusing the NR2B C terminus to Tat enhanced its affinity for PSD-95 PDZ2 by >100-fold (EC50, approximately 7 nM). IC50 values for Tat-NR2B9c inhibiting NR2A-NR2C/PSD-95 interactions (approximately 1-10 microM) and nNOS/PSD-95 interactions (200 nM) confirmed the feasibility of such inhibition. To determine which of the PDZ interactions of Tat-NR2B9c mediate neuroprotection, one of PSD-95, PSD-93, SAP97, SAP102, TIP1, or nNOS expression was inhibited in cortical neurons exposed to NMDA toxicity. Only neurons lacking PSD-95 or nNOS but not PSD-93, SAP97, SAP102, or TIP1 exhibited reduced excitotoxic vulnerability. Thus, despite the ubiquitousness of PDZ domain-containing proteins, PSD-95 and nNOS above any other PDZ proteins are keys in effecting NMDAR-dependent excitotoxicity. Consequently, PSD-95 inhibition may constitute a highly specific strategy for treating excitotoxic disorders.

Silicon wafers bearing microgrooved surfaces with various groove width, spacing, and depth were fabricated using microlithography. The orientation of rat Schwann cells along the direction of the grooves was measured at 24 h after seeding the cells. When the width/spacing of the grooves was fixed at 10/10 microm, the mean percentage of aligned cells was 12% for grooves of 0.5 microm depth, 15% for those of 1 microm depth, and 26% for those of 1.5 microm depth (P < 0.05). When the depth of grooves was fixed at 1.5 microm, the mean percentage of aligned cells increased from 26% for width/spacing 10/10 microm, to 33% for 10/20 microm or 20/10 microm, and up to 41% for 20/20 microm (P < 0.05). On the surface with grooves of width/spacing/depth = 20/20/1.5 microm and modified by laminin, the alignment at 24 h approached 60%, versus 51% for collagen-coated surface and 41% for uncoated surface (P < 0.05). At 48 h after seeding, about 66% of the cells were aligned on the above laminin-modified surface. The groove depth influenced orientation of Schwann cells significantly. The cell alignment on 20/20/3 microm microgrooved poly(D,L-lactide-co-glycolide) 90:10 (PLGA) surfaces transferred from silicon reached 72% at 48 h and 92% at 72 h (P < 0.05). Coating this surface with laminin enhanced cell alignment only in short term (67% vs. 62% at 24 h, P < 0.05). The cell alignment guided by surface microgrooves was time dependent., ((c) 2005 Wiley Periodicals, Inc.)

The B lymphocyte-induced maturation protein (Blimp-1) upregulates the expression of syndecan-1 and J chain and represses that of c-myc. We have transfected Blimp-1 into two sublines of the BCL1 B cell lymphoma that represent distinct stages of B cell development in secondary lymphoid tissues. After interleukin (IL)-2 and IL-5 stimulation, the BCL1 3B3 cells differentiate into centrocyte-like cells, whereas the BCL1 5B1b cells blast and appear to be blocked at the centroblast stage. This blasting effect and the increase in IgM secretion that follows it can be blocked by a dominant negative form of Blimp-1. At the same time, the ectopic expression of Blimp-1 in these partially activated cells induces an apoptotic response that also can be suppressed by the same dominant negative protein. A similar effect was noticed when Blimp-1 was expressed in the mature L10A and the immature WEHI-231 lines, indicating this may be a general effect at earlier stages of the B cell development, and distinct from the ability of Blimp-1 to induce maturation in late stages of differentiation. Truncation mutants indicate that the induction of the apoptotic response relies mainly on 69 amino acids within Blimp-1's proline-rich domain. We propose that Blimp-1 expression defines a checkpoint beyond which fully activated B cells proceed to the plasma cell stage, whereas immature and partially activated cells are eliminated at this point.

Penile erection is related to the integrity of penile tissue. In order to study the ultrastructural histopathological changes in penile erectile tissue in impotent men, biopsies were taken from 29 impotent and 5 normal patients during surgical treatment. Light microscopy revealed insignificant histological changes and various degrees of fibrotic change in the corpora cavernosa of impotent men, and electron microscopy revealed severe myopathic, fibrotic changes in the penile tissue. These non-specific changes could not be used to determine the aetiology of impotence, and the relationship between the ultrastructural appearances, the causes of impotence and the results of treatment was unclear. Further studies are required to establish the value of intracorporeal biopsy in selecting treatment for impotent patients.

From February to July in 1989, 47 patients came to our O.P.D. with the chief complaint of impotence. The average age was 48.3 +/- 10.7 y/o. We applied intracoporeal injection of prostaglandin PGE1 (20 mg); and evaluated its penile blood flow effect by color duplex scanning (Acuson 128). The erectile responses of the test showed that: 6 patients (12.8%) had normal response: and 16 patients (34%) had imperfect response. Altogether, the total positive response rate was 46.8%, and 25 patients (53.2%) showed impaired response. The onset of response was 9.1 +/- 3.6 minutes and the duration of erection was 59.2 +/- 24.7 minutes. The percentage of diameter change of both deep arteries after injection was Rt: 58.1 +/- 41.5%; left: 52.3 +/- 35.6%. The peak velocity of right cavernosal arterial flow after intracoporeal injection was 35.5 +/- 15.9 cm/sec; and that of the left side was 33.2 +/- 16.9 cm/sec. There was no correlation between the increment of peak velocity of the deep arterial flow and the erection grade. The same phenomenon was also found between the increased change in the diameter of the deep artery and the erection grade. 16 patients (34.1%) experienced tolerable pain during the procedure. Two patients (4.3%) experienced dizzines and discomfort due to venous leakage. No priapism was found. This study suggests PGE1 may be an excellent potential alternative to other vasoactive drug with less complication in the diagnosis and treatment of impotence. But the cost and stability were its shortcoming.(ABSTRACT TRUNCATED AT 250 WORDS)

The fetal heart rate (FHR) response to acute nonacidemic hypoxemia and to acute respiratory acidosis was studied in unanesthetized pregnant monkeys by means of chronically implanted catheters and electrodes. Average FHR and short- and long-term FHR variability were analyzed separately. The FHR response to either hypoxemia or hypercapnia consisted of slowing and increased variability. The slowing was more consistent with hypercapnia than with hypoxemia. Long-term FHR variability increased with both test stresses. The increase in short-term FHR variability was much greater in response to hypoxemia than to hypercapnia. Both the FHR slowing and the increases in variability in response to the test stresses were reduced by prior administration of atropine to the fetus.

The pre-ejection period (PEP) of the cardiac cycle was studied in 65 antepartum fetuses by means of a noninvasive technique which used simultaneous recordings of abdominal fetal electrocardiogram (FECG) and ultrasound fetal Doppler cardiogram (FDCG). Although most of the fetuses were products of high-risk pregnancies, 45 fetuses had uneventful perinatal courses. The PEP's from these fetuses demonstrated a significant positive relationship with gestational age (p is less than 0.01). Uterine contractions induced for antepartum stress testing of the fetus were founnd to prolong the PEP by approximately 9.1 per cent in five cases (four fetuses). The average PEP of antepartum fetuses between 38 and 40 weeks was shorter than that of intrapartum fetuses by approximately 9.5 per cent. Comparison between clinical outcome and the PEP's of the fetuses who were born within a week after the last determination of PEP revealed a strong correlation between prolonged PEP duration and abnormalities in the perinatal course.