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Few studies on the safety of gadolinium-based contrast agents have been performed in children with even fewer focusing on children younger than 2 years of age. To assess the safety of gadoterate meglumine (Dotarem) in patients younger than 2 years of age by evaluating adverse events following contrast administration. Pediatric patients younger than 2 years of age undergoing magnetic resonance imaging (MRI) with and without contrast were prospectively enrolled and received a weight-based intravenous dose of gadoterate meglumine (0.1 mmol/kg). The occurrence of adverse events was assessed at the time of injection, 2 h after MRI, and by phone contact using a standard questionnaire 24 h after MRI. Adverse events were documented including the time of onset, duration of symptoms, intensity, causality and subsequent outcome. Descriptive statistics were used to characterize patient information. One hundred fifty exams were completed in 150 patients (median age: 12.1 months, age range: 0.25–23 months; males: 56%). Almost all patients (97.3%) received sedation/anesthesia before and during MRI. Thirty-four adverse events were reported in 23 patients overall (15.3%; male: 73.9%; median age: 11 months, age range: 3–23 months). Within the initial 2 h after the injection, there was one report of transient flushing/warmth and one report of vomiting, the latter of which was related to drinking formula too soon after anesthesia. Twenty-two patients (14.7%), who had all received sedation/anesthesia, experienced minor adverse events within 24 h, most physiological. Fourteen patients (9.3%) reported emesis, eight (5.3%) reported transient flushing/warmth, seven (4.7%) reported nausea, one (0.7%) reported altered taste and one (0.7%) reported dizziness. No patient experienced anaphylaxis. Two patients (1.3%) reported allergic-like reactions, which consisted of wheezing or sneezing. No patient experienced adverse events directly related to gadoterate meglumine. Only two adverse events were reported to have occurred in the initial 2 h after the exam, while the rest were reported on the 24-h follow-up call. The higher reported rate of adverse events in this study may be related to concomitant sedation/anesthesia as well as to overreporting from parents on the 24-h follow-up questionnaire. The study confirms a good safety profile for gadoterate meglumine in this very sensitive population.

Pediatric patients with inflammatory bowel disease (IBD) are at increased risk of gadolinium deposition given the potential need for multiple contrast-enhanced magnetic resonance enterography (MRE) exams over their lifetime. To determine whether gadolinium-based contrast agents are necessary in assessing active bowel inflammation on MRE in pediatric patients with known or suspected IBD. We conducted a retrospective study of 77 patients (7–18 years; 68.8% male) with known (n=58) or suspected (n=19) IBD and endoscopy with biopsy performed within 30 days of MRE without and with contrast evaluated bowel and non-bowel findings. During three visual analysis sessions, two radiologists reviewed pre-, post-, and pre-/post-contrast MRE images. A third radiologist independently reviewed 27 studies to assess inter-reader reliability. We used Cohen kappa (κ), Fleiss kappa, (κF), McNemar test, and sensitivity and specificity to compare MRE readings to combined endoscopic/histopathological findings (the reference standard). The pre- and pre-/post-contrast-enhanced MRE vs. combined endoscopic/histopathological results had moderate agreement (85.7%; κ 0.713, P

Objective inpatient frailty assessments in decompensated cirrhosis are understudied. We examined the feasibility of inpatient frailty measurement, and associations with non-home discharge, readmission, and all-cause mortality among patients admitted for cirrhosis complications. We conducted a prospective study at three large liver transplant (LT) centers. Frailty was assessed using the Liver Frailty Index (LFI). Multivariable logistic and competing risk models evaluated associations between frailty and clinical outcomes adjusted for age and MELDNa. Inpatient frailty assessments were implemented among 211 patients. Median MELDNa was 21 (interquartile range [IQR]:15-27); 96 (45%) were women; 102 (48%) were LT waitlisted. At a median follow-up of 8.3 months, 29 (14%) had non-home discharge, 144 (68%) were readmitted, 70 (33%) underwent LT, and 44 (21%) died. A total of 124 (59%) patients were frail with median LFI of 4.71 ([IQR] 4.07-5.54). Patients with frailty were older (mean of 59 vs. 54 years), more likely to have chronic kidney disease (40% vs. 20%, P=0.002) and coronary artery disease (17% vs. 7%, P=0.03). Frailty was associated with hospital-acquired infections (8% among frail vs. 1% among non-frail, P=0.02). In multivariable models, LFI as a continuous measure was associated with non-home discharge (aOR 1.81 per 1-point increase, 95%CI: 1.14-2.86). Frailty (LFI ≥4.5) was associated with all-cause mortality in models accounting for LT as competing risk (sHR 2.4, 95%CI 1.13-5.11); results were similar with LFI as continuous variable (sHR 1.62 per 1-point increase, 95%CI 1.15-2.28). CONCLUSION: A brief, objective inpatient frailty assessment was feasible and predicted non-home discharge and mortality in decompensated cirrhosis. Inpatient point-of-care frailty assessment prior to hospital discharge can be useful for risk-stratification and targeted interventions to improve physical fitness and reduce adverse outcomes.

The purification of parasite-infected erythrocytes from whole blood containing leucocytes is crucial for many downstream genetic and molecular assays in parasitology. Current methodologies to achieve this are often costly and time consuming. Here, we demonstrate the successful application of a cheap and simple Non-Woven Fabric (NWF) filter for the purification of parasitized red blood cells from whole blood. NWF filtration was applied to the malaria-parasitized blood of three strains of mice, and one strain of rat, and to Babesia gibsoni parasitized dog blood. Before and after filtration, the white blood cell (WBC) removal rates and red blood cell (RBC) recovery rates were measured. After NWF filter treatment of rodent malaria-infected blood, the WBC removal rates and RBC recovery rates were, for Kunming mice: 99.51%±0.30% and 86.12%±8.37%; for BALB/C mice: 99.61%±0.15% and 80.74%±7.11%; for C57 mice: 99.71%±0.12% and 84.87%±3.83%; for Sprague-Dawley rats: 99.93%±0.03% and 83.30%±2.96%. Microscopy showed WBCs were efficiently removed from infected dog blood samples, and there was no obvious morphological change of B. gibsoni parasites. NWF filters efficiently remove leukocytes from malaria parasite-infected mouse and rat blood, and are also suitable for filtration of B. gibsoni-infected dog blood.

The volume-regulated anion channel (VRAC) is formed by LRRC8 proteins and is responsible for the regulatory volume decrease (RVD) after hypotonic cell swelling. Besides chloride, VRAC transports other molecules, for example, immunomodulatory cyclic dinucleotides (CDNs) including 2'3'cGAMP. Here, we identify LRRC8C as a critical component of VRAC in T cells, where its deletion abolishes VRAC currents and RVD. T cells of Lrrc8c

Objective The purpose of this study was to identify cardiac biomarkers of disordered eating as a function of diagnostic subtype as assessed via self-report inventory. Method Mean heart rate (HR), systolic and diastolic blood pressure, mean R wave amplitude (mV), mean T wave amplitude (mV), QTc interval (sec), Tpeak-Tend interval prolongation (sec), QTc interval prolongation (sec), QRS prolongation (sec), and spectral indicators of cardiac dysfunction (LF/HF spectral ratio, HF spectral power) were assessed via electrocardiography among women with no eating disorder symptoms (n = 32), subclinical eating disorder symptoms (n = 92), anorexia nervosa (n = 7), bulimia nervosa (n = 89), binge eating disorder (BED: n = 20), and other specified feeding and eating disorders (OSFED: n = 19). Results MANOVA results showed statistically significant group differences. Follow-up tests revealed significantly decreased mean R wave amplitude among participants with self-indicated clinical (bulimia nervosa, binge eating disorder) and subclinical forms of disordered eating compared to asymptomatic controls. Discussion Results suggest decreased mean R wave amplitude is a promising cardiac biomarker of disordered eating.

OBJECTIVE: To detail a novel technique for marking renal tumors with intravenous indocyanine green (ICG) during laparoscopic partial nephrectomy, and to investigate the feasibility and safety of this technique with the use of near-infrared fluorescence imaging. METHODS: Between July 2019 and January 2020, 25 consecutive cases with renal masses underwent intraoperative ICG tumor marking laparoscopic partial nephrectomy, at the department of urology in Peking University Third Hospital by the same surgeon. The key benefits included quick intraoperative identification of the mass with improved visualization and real-time control of resection margins by the ICG Immunofluorescence imaging technique. Clinical data were prospectively collected in our institutional database. Perioperative, pathological, and clinical outcomes of the partial nephrectomy were assessed. Measurement data with normal distribution and count data were respectively described as M(range) and percentage. Among these cases, 16 cases were male and 9 cases female, The median body mass index was 25.4 (20.0-35.4) kg/m(2). The average age was 54 (29-77) years. The maximum tumor diameter was 2.75(1.30-5.20) cm. The R.E.N.A.L score was 7.5 (5.0-10.0).The tumor locations were distributed with upper pole (11, 42%), middle (6, 23%), and lower pole (9, 35%).The clinical stages of the tumor were described as follows: T1aN0M0 (23, 88.5%), T1bN0M0(2, 7.7%), T2aN0M0 (1, 3.8%). RESULTS: All the 25 cases were performed 26 times with intraoperative ICG tumor marking laparoscopic partial nephrectomy. There were no allergy, infection and other complications with intravenous indocyanine green. The surgical procedure was successful in all the patients. No conversion and blood transfusion were needed. All the cases of the surgical margin were negative. Overall the operative time was 136 (50-247) min and warm ischemia time was 14 (7-30) min.The estimated blood loss was 50 (10-400) mL and the hospital stay was 5.5 (3.0-31.0) days. One case with perirenal hematoma, one case with urine leak, one with respiratory failure and deep venous thrombosis. All of these cases were cured by the corresponding treatment. The others had no severe complications. There was no tumor recurrence and metastasis during the follow up with 4 to 10 months. CONCLUSION: ICG marking and near-infrared fluorescence imaging technology has now emerged as a safe, feasible and useful tool that may facilitate laparoscopic partial nephrectomy.

Postpartum uterine contraction pain has not been studied sufficiently. We aimed to assess the incidence, intensity, and risk factors for postpartum uterine contraction pain.Women with singleton pregnancies who delivered vaginally were enrolled in this prospective, observational, single-institution study. We determined the numerical rating scale (NRS) score (0 to 10-point) for uterine contraction pain at 6, 12, 24, and 48 h after delivery. Generalized mixed modeling was used to identify the risk factors for significant postpartum uterine contraction pain (NRS score ≥3). We compared the incidence and severity of postpartum uterine contraction pain between nulliparous and multiparous women.Two hundred and sixty-five nulliparous and 139 multiparous women were included. Forty-seven percent (188/404; 95% confidence interval [CI] 41.7% to 51.4%) of women presented with significant uterine contraction pain within 48 h of delivery. The generalized mixed model showed that nulliparous women had a lower risk of significant postpartum uterine contraction pain compared with multiparous women (odds ratio [OR] 0.33, 95% CI 0.17 to 0.61; P0.001). Women with a history of dysmenorrhea had higher risk of significant postpartum uterine contraction pain (OR 1.77, 95% CI 1.12 to 2.79; P=0.014). Both nulliparous and multiparous women reported more intense uterine contraction pain while breastfeeding (P0.001).Postpartum uterine contraction pain is common and severe in some women. Parity and history of dysmenorrhea are significant risk factors for significant postpartum uterine contraction pain.

Colorectal cancer (CRC), one of the common malignant cancers in the world, is caused by accumulated alterations of genetic and epigenetic factors over a long period of time. Along with that protein-coding genes being identified as oncogenes or tumor suppressors in CRC, a number of lncRNAs have also been found to be associated with CRC. Considering the important regulatory role of lncRNAs, the first goal of this study was to identify CRC-associated lncRNAs from a public database. One such lncRNA, LINC00472, was verified to be downregulated in CRC cell lines and cancer tissues compared with adjacent tissues. In addition, the down-regulation of LINC00472 seemed to be caused by DNA hypermethylation at its promoter region. Furthermore, the expression of LINC00472 and DNA methylation of promoter were significantly correlated with clinicopathological features. And DNA hypermethylation of LINC00472 may serve as a better diagnostic biomarker than its expression for CRC. Finally, we predicted the functions of LINC00472 and constructed a regulatory network and found LINC00472 may be involved in cell cycle and cell proliferation processes. Our results may provide a clue to further research into the function and regulatory mechanism of LINC00472 in CRC.

Summary Objective A recent genome-wide association study reported significant associations of genetic variants within the ALDH1A2 gene with osteoarthritis (OA) of the hand in European populations. However, these findings have not been well generalized to other joints, or to other populations. Methods We performed a two-stage population-based case–control study including 196 non-post traumatic knee OA cases and 442 controls in the first stage and independent 143 non-post traumatic knee OA cases and 238 controls in the second stage in a Chinese population by genotyping eight tagging polymorphisms in ALDH1A2 . Results In the first stage, the single nucleotide polymorphism (SNP) rs4238326 was found to be potentially associated with knee OA risk (additive model: odds ratio [OR] = 0.70; 95% confidence interval [95% CI] = 0.49–1.01; P = 0.055), which was further confirmed in the second stage with similar effect (additive model: OR = 0.60; 95% CI = 0.38–0.95; P = 0.029). After combining the two stages, we found that the variant C allele of rs4238326 was probably associated with decreased risk of knee OA (additive model: OR = 0.65; 95% CI = 0.49–0.86; P = 0.003). Furthermore, interaction analyses showed that rs4238326 interacted multiplicatively with age to contribute to knee OA risk (interaction P = 0.041). Conclusions These findings indicate that the SNP rs4238326 in ALDH1A2 gene may potentially modify individual susceptibility to knee OA in the Chinese population. Beyond that, further studies are warranted to validate and extend our findings, and future functional studies are required to clarify the possible mechanisms.

Background: Morphine is a common analgesic often used to manage chronic pain, especially for patients with pain due to malignancies. Since UGT2B7 plays an important role in the metabolism of morphine, UGT2B7 gene mutation may influence the efficacy of morphine in patients with cancer being treated by this medication. Aims: The aim of this study is to investigate the relationship between the polymorphisms of UGT2B7 and the efficacy of morphine treatment on cancer pain among the Chinese Han population. Materials and Methods: A total of 120 patients with cancer pain were enrolled in this study. Morphine was administrated through patient-controlled analgesia infusion pump, and the visual analog score (VAS) was used for pain assessment at 0.5, 4, 6, 12, 24, 48, and 72-h post morphine treatment, respectively. The plasma concentration of morphine and genetic polymorphism of UGT2B7 C802T and G221T was analyzed, respectively. Results: The frequencies of UGT2B7 C802T were CC: 13.33%, CT: 45% and TT: 41.67%, and the frequencies of UGT2B7 G221T were GG: 76.67%, GT: 22.5% and TT: 0.83%. Moreover, the VAS score of patients with either C802T CT or TT was significantly higher than that in patients with C802T CC. However, no difference of VAS scores was observed between patients carrying G221T GG and patients carrying G221T GT. The plasma concentration of morphine for patients with the C802T CC was significantly lower than that in patients carrying C802T CT or TT, while there was no significant difference in the level of morphine between patients with G221T GG and G221T GT. Conclusion: The polymorphism of UGT2B7 C802T, but not UGT2B7 G221T, has been associated with the efficacy of morphine treatment on cancer pain among Chinese Han population.

Failing to repair DNA double-strand breaks by either nonhomologous end joining (NHEJ) or homologous recombination (HR) poses a threat to genome integrity, and may have roles in the onset of aging and age-related diseases. Recent work indicates an age-related decrease of NHEJ efficiency in mouse models, but whether NHEJ and HR change with age in humans and the underlying mechanisms of such a change remain uncharacterized. Here, using 50 eyelid fibroblast cell lines isolated from healthy donors at the age of 16–75 years, we demonstrate that the efficiency and fidelity of NHEJ, and the efficiency of HR decline with age, leading to increased IR sensitivity in cells isolated from old donors. Mechanistic analysis suggests that decreased expression of XRCC4, Lig4 and Lig3 drives the observed, age-associated decline of NHEJ efficiency and fidelity. Restoration of XRCC4 and Lig4 significantly promotes the fidelity and efficiency of NHEJ in aged fibroblasts. In contrast, essential HR-related factors, such as Rad51, do not change in expression level with age, but Rad51 exhibits a slow kinetics of recruitment to DNA damage sites in aged fibroblasts. Further rescue experiments indicate that restoration of XRCC4 and Lig4 may suppress the onset of stress-induced premature cellular senescence, suggesting that improving NHEJ efficiency and fidelity by targeting the NHEJ pathway holds great potential to delay aging and mitigate aging-related pathologies.

Y chromosomes display population variation within and between species. Co-evolution within populations is expected to produce adaptive interactions between Y chromosomes and the rest of the genome. One consequence is that Y chromosomes from disparate populations could disrupt harmonious interactions between co-evolved genetic elements and result in reduced male fertility, sterility or inviability. Here we address the contribution of 'heterospecific Y chromosomes' to fertility in hybrid males carrying a homozygous region of Drosophila mauritiana introgressed in the Drosophila simulans background. In order to detect Y chromosome-autosome interactions, which may go unnoticed in a single-species background of autosomes, we constructed hybrid genotypes involving three sister species: Drosophila simulans, D. mauritiana, and D. sechellia. These engineered strains varied due to: (i) species origin of the Y chromosome (D. simulans or D. sechellia); (ii) location of the introgressed D. mauritiana segment on the D. simulans third chromosome, and (iii) grandparental genomic background (three genotypes of D. simulans). We find complex interactions between the species origin of the Y chromosome, the identity of the D. mauritiana segment and the grandparental genetic background donating the chromosomes. Unexpectedly, the interaction of the Y chromosome and one segment of D. mauritiana drastically reduced fertility in the presence of Ysim, whereas the fertility is partially rescued by the Y chromosome of D. sechellia when it descends from a specific grandparental genotype. The restoration of fertility occurs in spite of an autosomal and X-linked genome that is mostly of D. simulans origin. These results illustrate the multifactorial basis of genetic interactions involving the Y chromosome. Our study supports the hypothesis that the Y chromosome can contribute significantly to the evolution of reproductive isolation and highlights the conditional manifestation of infertility in specific genotypic combinations.

This study aimed to assess the efficacy of a rural community-based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China. This 18-year cluster-randomized controlled trial encompassing 15 villages included 1008 patients (454 men and 40 women in the intervention group [mean age, 54 ± 10 years]; 482 men and 32 women in the control group [mean age, 53 ± 10 years]) with confirmed COPD or at risk for COPD. Villages were randomly assigned to the intervention or the control group, and study participants residing within the villages received treatment accordingly. Intervention group patients took part in a program that included systematic health education, smoking cessation counseling, and education on management of COPD. Control group patients received usual care. The groups were compared after 18 years regarding the incidence of COPD, decline in lung function, and mortality of COPD. COPD incidence was lower in the intervention group than in the control group (10% vs 16%

Introduction As one of the key molecules in the extracellular matrix in human conceptus, hyaluronan (HA) has been receiving particular attention. Here, we have investigated the expression and regulation of different molecular weight HA on the biological behaviors of primary human trophoblasts during the first trimester of pregnancy. Methods The expression of HA and HA synthetase (HAS) by human first trimester trophoblasts was analyzed in placentae from normal pregnancy or miscarriage by immunochemistry and real-time RT-PCR, respectively. ELISA was used to measure the secretion of HA by primary trophoblasts. The effects of HA on the proliferation, apoptosis and invasiveness of trophoblasts were examined. We also investigated the signaling pathways involved in HA activation in human trophoblasts. Results The higher HAS2 expression and HA secretion were observed in normal villi than that of miscarriage, and the primary trophoblasts secreted HA continuously. High molecular weight HA (HMW-HA) and medium molecular weight HA (MMW-HA) promoted proliferation and invasiveness while inhibited apoptosis of trophoblasts. However, low molecular weight HA (LMW-HA) had no obvious effect on the growth or invasiveness of human trophoblasts. In addition, HMW-HA showed more efficiently than MMW-HA on the growth while MMW-HA displayed a more obvious effect on the invasiveness of trophoblasts than HMW-HA. HMW-HA activated PI3K/AKT and MAPK/ERK1/2 signaling pathways in trophoblasts. Blocking PI3K/AKT or MAPK/ERK1/2 signaling inhibited the HA-upregulated growth and invasiveness of human trophoblasts. Conclusion Our results suggest that higher level and greater molecular mass of HA can promote trophoblast growth and invasion in an autocrine manner, which was beneficial to placentation and maintenance of human early pregnancy.

The aim of this study is to evaluate clinical benefits of recombinant adenoviral human p53 (rAd-p53) gene therapy combined with radiotherapy in prevention of oral cancer recurrence after a radical resection. A total of 51 patients with tongue cancer (TCa) and 56 patients with gingival carcinoma (GCa) satisfying the inclusion criteria were randomly assigned to two groups: the experiment group (EG) and the control group (CG). The EG group received multipoint injections of rAd-p53 into the surgical wound surface at a dose of 1 × 10¹² viral particles after a radical resection. Patients in both EG and CG were given radiotherapy at a total dose of 60 Gy at 3 weeks after surgery. All these patients were followed up for at least 3 years. Two cases (2/27) of TCa and 2 (2/30) in GCa patients had a local recurrence in EG, but 8 (8/24) TCa and 8 (8/26) GCa patients in CG had a local recurrence. Both recurrent rates of TCa (33.3%) and GCa (30.8%) in CG are statistically significantly higher than those of TCa (7.4%) and GCa (6.7%) in EG, respectively. The overall recurrent rate in EG is 7%, which is also statistically significantly lower than that (32%) in CG. The 3-year overall survival (OS) rate and 3-year disease-free survival (DFS) rate of EG is 100% and 93%, respectively. The 3-year OS and DFS rates of CG are 94 and 68%, respectively. Mild or medium fever and flu-like symptoms were more frequently observed in EG and were considered to be associated with application of rAd-p53. Post-tumorectomy wound surface injection of rAd-p53 combining with radiotherapy is a safe and effective regimen for the patients with TGa or GCa.

Introduction As a calcineurin inhibitor in T-cell activation, cyclosporine A (CsA) has provided the pharmacologic foundation for organ transplantation. We have previously demonstrated that CsA promotes trophoblast growth and invasion in vitro . Here, we further investigated the regulation of CsA on trophoblast migration and the intracellular signaling pathways involved. Methods We evaluated the migration of human primary trophoblasts by using transwell migration assay. CsA-mediated induction of nuclear factor-kappa B (NF-κB) was evaluated by cotransfection with luciferase reporter constructs and luciferase activity assays. Results Treatment with CsA-promoted migration of primary trophoblasts and the HTR8 cell line in a dose-dependent manner. CsA also increased NF-κB-transcriptional activity in trophoblasts in time- and dose-dependent manners. Pharmacologically inhibiting mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) 1/2 signaling with U0126 attenuated the CsA-induced cell migration and NF-κB activity in trophoblasts. Furthermore, pretreatment with PDTC, a specific NF-κB inhibitor, inhibited the CsA-induced migration of trophoblasts in dose-dependent manners. Although NFAT activation by ionomycin via calcineurin is accompanied by increased transactivation of NF-κB, pretreatment with the NFAT inhibitor did not affect NF-κB-transcriptional activity. Interestingly, ionomycin and CsA synergize to transactivate NF-κB. Ionomycin-inhibited basal migration of trophoblasts, and pretreatment with CsA reversed the ionomycin-inhibited trophoblast migration. However, the NFAT inhibitor increased basal migration, but not CsA-induced migration, of trophoblasts. Conclusion These observations indicate that both the MAPK/ERK/NF-κB pathway and Ca 2+ /calcineurin/NFAT pathways are involved in the CsA-promoted trophoblast migration. Our findings may help expand the clinical applications of this drug in trophoblast disorder.

The relationship between blood pressure variability (BPV) and stroke recurrence is controversial. This study aimed to evaluate the predictive value of short-term and long-term BPV for stroke recurrence. The data from blood pressure and clinical outcome in TIA or ischemic stroke (BOSS) study included participants with acute ischemic stroke or transient ischemic attack (TIA) within 7 days after onset. Short-term BPV was measured by 24-h ambulatory BP measurement during hospitalisation. Long-term BPV, based on home blood pressure measurement, was measured by patients or their families from discharge to 90 days after qualifying events onset (twice daily). Variability for systolic blood pressure (SBP) was assessed as the s.d., coefficients of variance (CV). The clinical outcome was recurrent stroke within 1 year. Cox proportional hazards models were used to test the association of short-term BPV, long-term BPV and stroke recurrence. Among 1764 participants, the mean age was 62.45±10.99 years, and 32.1% were females, during 1-year follow-up, 106 (6.0%) participants experienced recurrent stroke. Indices of long-term BPV were significantly associated with stroke recurrence (s.d.: adjusted HR: 1.939, 95% CI: 1.122-3.351; CV: adjusted HR 1.955, 95% CI: 1.174-3.255), independent of mean SBP. However, all indices of short-term BPV (s.d., CV) were not associated with stroke recurrence (s.d.: adjusted HR: 1.245, 95% CI: 0.680-2.280; CV: adjusted HR: 1.142, 95% CI: 0.640-2.038). In conclusion, long-term variation of SBP is a better predictor than short-term variation of SBP for recurrent stroke after acute ischemic stroke or TIA.

To evaluate the efficacy of topical voriconazole in patients with fungal keratitis caused by different fungal species.Interventional case series. Eighty-four patients aged 18 years or older from central China with confirmed fungal keratitis who presented at the outpatient department of Henan Eye Institute were enrolled in the study. The patients underwent in vivo confocal scanning laser microscopy examination, coneal scraping and microscopic examination and fungal culture, and then received topical voriconazole, closed curative effects were conducted. The sensitivity of three different diagnostic techniques, spectrum of the fungi, cure rate for fungal corneal infection related to each species were analyzed.In our study, 84 patients were diagnosed with fungal keratitis based on clinical symptoms, and results of at least one of the examinations of in vivo confocal scanning laser microscopy, conventional smear, and corneal scraping culture and the sensitivity were 92.85%(78/84), 85.71%(72/84), 84.52%(71/84)respectively. In viro confocal scanning laser microscopy. Successful management was achieved in 83.33% of the patients. Topical voriconazole treatment failed in 14 patients(16.67%), who required surgical treatment. In 36 patients with Fusarium corneal infections, 26(72.22%)were successfully treated with topical voriconazole; however, in 18 patients with Aspergillus corneal infections and 7 patients with Alternaria corneal infections, 94.44% and 100.00% of them were successfully treated, respectively. In a case-based dynamic tracking study, in vivo confocal microscopy provided real-time dynamic detection of surviving hyphae. The existence of hyphae was(38.35±17.32)days for Fusarium,(25.00±16.11)days for Aspergillus,(21.00±4.36)days for Alternaria, and(41.50±31.68)days for the focus in the deep stroma. The duration of treatment was similar for all four groups.Topical application of voriconazole is on effective method for the freatment of fungal keratitis Topical voriconazole is highly effective for fungal keratitis caused by Alternaria spp. and Aspergillus, however, for Fusarium, it is relatively low effective. (Chin J Ophthalmol, 2016, 52: 657-662).

Though various clinical conditions of aspergillosis can occur, depending essentially on the host’s immunological status, the focus of research in North American and European countries has mainly been on invasive pulmonary aspergillosis in immunocompromised patients. There are, however, also many problems to overcome in chronic forms of aspergillosis. One of those problems is that there are no codified treatment guidelines for chronic pulmonary aspergillosis (CPA). Especially in Japan, this issue is more serious, because there are more cases with CPA due to the many aged people with past history of tuberculosis. Several clinical cases and case series have reported the usefulness of the various antifungal agents that are available. The new triazole, voriconazole, in particular, seems to be effective in the treatment of CPA. The aim of the present study is to evaluate the efficacy and safety of voriconazole in the treatment of CPA in non-immunocompromised patients. We conducted a prospective, open-label, non-comparative, multicenter study over a 2-year period. For inclusion in the study, patients with confirmed or probable CPA were recruited in 11 hospitals of the National Hospital Organization in Japan. Clinical, radiological, serological, and mycological data were collected at baseline and 12 weeks after treatment or at the end of treatment. Among 77 patients enrolled in the study, 71 patients (mean age 65.9 years, 56 males and 15 females) were eligible for the study. All of the eligible patients presented with underlying lung diseases, including sequelae of tuberculosis (n = 35), non-tuberculous mycobacterial lung disease (n = 8), chronic obstructive pulmonary disease (COPD) (n = 8), interstitial pneumonia (n = 7), cystic lung disease (n = 4), pneumothorax (n = 3), bronchial cancer (n = 1), and others (n = 5). Voriconazole was indicated in 48 cases (68 %) as the first-line treatment for CPA and 23 patients previously received other antifungal therapies. Based on a composite of clinical, radiologic, serological, and mycologic criteria, good response was seen in 43 patients (60.6 %), no response was observed in 19 patients (26.8 %), and 4 cases (5.6 %) got worse. Five patients (7.0 %) were unassessable for efficacy. The common adverse events were visual disturbances (17 patients, 23.9 %), abnormal liver function test results (12 patients, 16.9 %), adverse psychological effects (3 patients, 4.2 %), and others (10 patients, 14.0 %). Treatment with voriconazole had to be stopped in 2 cases (2.8 %) because of serious adverse events (abnormal liver function test results). There was no association between adverse effects and trough voriconazole levels in serum. In Japan, voriconazole provides effective therapy of CPA in non-immunocompromised patients with an acceptable level of toxicity.

Dietary supplements containing black cohosh are alternatives to conventional hormone replacement therapy in menopause. This study investigates the maximum tolerated dose of a 75% ethanol extract of black cohosh and determines the pharmacokinetics of one of its most abundant triterpene glycosides, 23-epi-26-deoxyactein. Single doses of black cohosh extract containing 1.4, 2.8, or 5.6 mg of 23-epi-26-deoxyactein were administered to 15 healthy, menopausal women. Serial blood samples and 24-h urine samples were obtained; blood chemistry, hormonal levels, and 23-epi-26-deoxyactein levels were determined. No acute toxicity or estrogenic hormone effects were observed. Pharmacokinetic analyses of 23-epi-26-deoxyactein in sera indicated that the maximum concentration and area under the curve increased proportionately with dosage, and that the half-life was ~2 h for all dosages. Less than 0.01% of the 23-epi-26-deoxyactein was recovered in urine 24 h after administration. No phase I or phase II metabolites were observed either in clinical specimens or in vitro.

In this study, polymorphisms of human leukocyte antigen (HLA) class I (A, B, and Cw) and class II (DRB1) loci were analyzed in an isolated Han population living in Fengyandong in the Yunnan province of Southwest China (FYDH) using a high-resolution polymerase chain reaction-Luminex typing method. A total of 13 A, 26 B, 15 Cw, and 23 DRB1 alleles of HLA were found in FYDH. The frequencies of A*1101, A*0207, A*2402, B*4601, B*1502, Cw*0102, Cw*0801, DRB1*0901, and DRB1*1202 were >10%. The following haplotypes were common with frequencies >5%: three A-B, four Cw-B, two B-DRB1, two A-B-DRB1, three A-B-Cw, two B-Cw-DRB1, and two A-B-Cw-DRB1 phylogenetic tree and multidimensional scaling analysis based on HLA-A, -B, and -DRB1 allele frequencies of 18 Han populations suggested that FYDH was an isolated Han population, but the analytic result also provided a suggestion that FYDH was genetically related to Chinese Southern Han. According to the characteristics of the HLA allele and haplotype distributions and significantly reduced allelic and haplotypic diversity in FYDH, we deduced that genetic drift and/or selection and subsequent geographic isolation had influenced the distribution characteristics of the HLA gene in FYDH. In addition, significantly reduced allelic and haplotypic diversity in FYDH makes it an ideal homogenous population and very useful model for future investigations of issues related to immunogenetic diseases in the Han population.

To determine whether hot flashes, depressed mood, sleep, cognitive and sexual symptoms correlate with urinary follicle-stimulating hormone (FSH), estrone (E(1)G), and testosterone (T) and with each other during the menopausal transition and early postmenopause (PM).Forty-one women who transitioned from middle or late transition stage to PM rated symptoms and provided monthly urine specimens as part of a longitudinal study of the menopausal transition.Correlations between endocrine levels and symptom severity ratings over time revealed that hot flash severity was significantly and positively related to FSH and negatively to E1 G. Vaginal dryness was positively correlated with FSH and negatively correlated with T. Decreased sexual desire was correlated negatively with E(1)G levels. Forgetfulness was positively correlated with FSH; difficulty concentrating was negatively correlated with T. Severity of sleep symptoms and depressed mood were not correlated with E(1)G, FSH, or T. Correlations among the symptoms revealed that severity of hot flashes was associated with sleep disruption and forgetfulness. Depressed mood was correlated with sleep disruption, difficulty concentrating, and decreased sexual desire but not with hot flashes or vaginal dryness. Awakening during the night was correlated with decreased sexual desire and vaginal dryness, as well as hot flashes. Forgetfulness was associated with hot flashes and difficulty concentrating, whereas difficulty concentrating was associated with depressed mood and early awakening.Symptoms many women experience during the menopausal transition and early PM are related to different endocrine levels (FSH, E(1)G, and T).

The fat mass- and obesity-associated gene (FTO) is involved in energy metabolism, but little is known about the chicken FTO gene. The objective of the current study was to detect chicken FTO expression patterns in the hypothalamus, liver, and skeletal muscle during development, and analyze the effects of age and breed on FTO expression. Real-time quantitative polymerase chain reaction results revealed that chicken FTO mRNA was expressed in all of the tissues tested. Chicken FTO exhibited tissue- and breed-specific patterns in the recessive White Plymouth Rock chicken and the Qingyuan partridge chicken. The highest FTO expression level was in the hypothalami of 1-week-old chicks. FTO mRNA was expressed more in the breast muscles and livers of recessive White Plymouth Rock chickens than those of Qingyuan partridge chickens at 1 and 8 weeks of age. These results indicate that FTO probably plays a significant role in energy metabolism at 1 week old, when chicks have undergone metabolic adaptations from yolk dependence to the utilization of exogenous feed.