OBJECTIVE: To explore the clinical features and genetic basis for a Chinese pedigree diagnosed with congenital glycosylation disease (CGD). METHODS: Clinical manifestations of two brothers were analyzed. Whole exome sequencing was carried out for the sib pair. Suspected variants were verified by Sanger sequencing. RESULTS: Both the proband and her younger brother were found to carry compound heterozygous variants of the PMM2 gene, which included a known pathogenic mutation of c.395T>C (p.I132T) and a previously unreported c.448-1(delAG) in the 5' end of exon 6 of the gene. CONCLUSION The compound heterozygous variants of the PMM2 gene probably underlay the CGD in the sib pair.
Asians/genetics* ; China ; Female ; Glycosylation ; Humans ; Male ; Mutation ; Pedigree ; Whole Exome Sequencing

Objective To explore the effect of the expressive psychotherapy on the feeling of inadequacy and loneliness of inpatients with chronic schizophrenia.MethodsTotally 120 chronic schizophrenia inpatients met recruited criteria were randomly divided into study group(n=60) and control group(n=60) according to random number table.57 patients in each group finished all the follow-ups finally.The patients in two groups were received normal medications while the patients in intervention group also attended expressive psychotherapy.All the patients were assessed at baseline,6 weeks and 12 weeks of treatment with the feeling of inadequacy scale (FIS) and the status and trait loneliness scale (STLS).Results(1) The FIS score(F=225.19,P<0.01),STLS total score(F=225.20,P<0.01),STLS status score(F=240.40,P<0.01) and STLS trait score(F=106.75,P<0.01) decreased significantly in both groups after intervention.(2) The FIS score of study group was much lower than those of control group at the at 6-week-follow-up(4.93±20.86,57.89±20.48,t=-2.250,P<0.01) and 12-week-follow-up(38.43±17.50,57.21±22.98,t=-4.900,P<0.01).(3) After 6 weeks treatment and 12 weeks treatment,STLS total score(6 weeks:(54.32±12.30) vs (68.46±15.53),t=-5.425,P<0.01,12 weeks:(44.16±10.81) vs (65.75±16.26),t=-8.386,P<0.01),STLS status score (6 weeks:(25.95±6.41) vs (34.31±7.91),t=-6.239,P<0.01,12 weeks:(19.15±5.49) vs (32.58±8.45),t=-10.103,P<0.01) and STLS trait score (6 weeks:(28.37±6.73) vs (34.15±8.45),t=-4.138,P<0.01,12 weeks:(25.00±6.18) vs (33.15±8.22),t=-6.019,P<0.01) in study group were lower than those in control group,and the difference was statistically significant.ConclusionExpressive psychotherapy can effectively improve the loneliness and inadequacy of patients with chronic schizophrenia.

Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of AR, TGF-beta1, alpha-SMA and collagen I was analyzed by immunohistochemisty, real-time PCR or western blot. In vivo, epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-beta1, AR, alpha-SMA and collagen I (both mRNA and protein). In vitro, epalrestat remarkably attenuated proliferation of pulmonary fibroblasts and expression of alpha-SMA and collagen I induced by TGF-beta1, and this inhibitory effect of epalrestat was accompanied by inhibiting AR expression. Knockdown of AR gene expression reversed TGF-beta1-induced proliferation of fibroblasts, up-regulation of alpha-SMA and collagen I expression. These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis, and epalrestat inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.
Airway Remodeling ; Aldehyde Reductase* ; Animals ; Asthma ; Bleomycin ; Blotting, Western ; Bromodeoxyuridine ; Collagen ; Diabetic Neuropathies ; Fibroblasts ; Fibrosis ; Flow Cytometry ; Gene Expression ; Negotiating ; Pulmonary Fibrosis* ; Rats* ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Transforming Growth Factor beta1 ; Up-Regulation

Objective To study the effects and mechanism of calycosin on oxidative stress andβ-cell apoptosis induced by streptozotocin (STZ). Methods RIN-m5F cells were divided into 5 groups:control group, STZ group, STZⅠgroup, STZⅡgroup and STZⅢgroup. The control group did not receive any treatment, while streptozotocin was added to the final concentration of 10 mmol/L in STZ group, STZⅠgroup, STZⅡgroup and STZⅢgroup. After the incubation with STZ for 6 h, calycosin was added to a final concentration of 10, 50 and 100 μmol/L in STZⅠgroup, STZⅡgroup and STZⅢgroup respectively. The cell viability and apoptosis was detected by CCK-8, LDH, caspase 3 and Tunel assay. The intracellular oxidative stress was measured using mitochondrial membrane potential, DCFH-DA, SOD activity and malondialdehyde levels assay. RIN-m5F cells were divided into control group, calycosinⅠgroup, calycosinⅡgroup and calycosinⅢgroup, which were treated with different concentrations (0,10, 50 and 100 μmol/L, respectively) of calycosin. The expression of NF-E2-related factor 2(Nrf2) in RIN- m5F cells was detected by Western blot. The translocation of Nrf2 was detected by immunofluorescence. In RIN-m5F cells were divided intoⅢgroup andⅣgroup,Ⅳgroup was pre-treated with protein kinase C(PKC) inhibitor. The effects of calycosin on Nrf2 translocation, oxidative stress and apoptosis were also observed. Results STZ could induce the accumulation of reactive oxygen species and apoptosis in RIN-m5F cells. Calycosin did not affect normal RIN-m5F cells, whereas it reduced the oxidative stress and apoptosis induced by STZ in a dose-dependent manner. The expression of Nrf2 in RIN-m5F cells was not affected by calycosin, whereas it promoted the translocation of Nrf2 into nucleus. The ability of calycosin promoting Nrf2 translocation was decreased after PKC inhibitor treatment, and PKC inhibitor could also significantly attenuate the anti-oxidant and anti-apoptotic ability of calycosin. Conclusions This study shows that calycosin may play an anti-oxidative and anti-apoptotic role by activating PKC to promote Nrf2 translocation, which is expected to be used as a new clinical drug for the prevention and treatment of diabetes mellitus.

Objective To explore the clinical and genetic characteristics of complex glycerol kinase deficiency (GKD). Methods The clinical data of 2 cases of complex GKD were analyzed and the related literatures were reviewed. Results Both cases were male onset in neonatal period, and had hypocorticalism (hyponatremia, hyperkalemia, dehydration), hypercreatine kinasemia, and pseudotriglyceridemia. Gene detection suggested that there was gene deletion in chromosome Xp21 region. In the follow-up, one case had good control of the disease and one died of infection. Conclusions Complex GKD is an X-linked recessive hereditary disease. It is rare and complicated, and is easily misdiagnosed. Early diagnosis and treatment are beneficial to improve the prognosis.

OBJECTIVE: To investigate the association of myocardial blood flow (MBF) quantified by dynamic computed tomography (CT) myocardial perfusion imaging (MPI) with troponin level and left ventricle (LV) function in patients with ST-segment elevated myocardial infarction (STEMI). MATERIALS AND METHODS: Thirty-five STEMI patients who successfully had undergone reperfusion treatment within 1 week of their infarction were consecutively enrolled. All patients were referred for dynamic CT-MPI. Serial high-sensitivity troponin T (hs-TnT) levels and left ventricular ejection fraction (LVEF) measured by echocardiography were recorded. Twenty-six patients with 427 segments were included for analysis. Various quantitative parameters derived from dynamic CT-MPI were analyzed to determine if there was a correlation between hs-TnT levels and LVEF on admission and again at the 6-month mark. RESULTS: The mean radiation dose for dynamic CT-MPI was 3.2 ± 1.1 mSv. Infarcted territories had significantly lower MBF (30.5 ± 7.4 mL/min/100 mL versus 73.4 ± 8.1 mL/min/100 mL, p < 0.001) and myocardial blood volume (MBV) (2.8 ± 0.9 mL/100 mL versus 4.2 ± 1.1 mL/100 mL, p = 0.044) compared with those of reference territories. MBF showed the best correlation with the level of peak hs-TnT (r = −0.682, p < 0.001), and MBV showed a moderate correlation with the level of peak hs-TnT (r = −0.437, p = 0.026); however, the other parameters did not show any significant correlation with hs-TnT levels. As for the association with LV function, only MBF was significantly correlated with LVEF at the time of admission (r = 0.469, p = 0.016) and at 6 months (r = 0.585, p = 0.001). CONCLUSION: MBF quantified by dynamic CT-MPI is significantly inversely correlated with the level of peak hs-TnT. In addition, patients with lower MBF tended to have impaired LV function at the time of their admission and at 6 months.
Blood Volume ; Echocardiography ; Heart Ventricles ; Humans ; Infarction ; Myocardial Infarction ; Myocardial Perfusion Imaging ; Reperfusion ; Stroke Volume ; Troponin T ; Troponin

Lenvatinib mesylate (LF), a multi-target tyrosinase inhibitor mainly used in the treatment of a variety of cancers, has low oral bioavailability mainly due to its gelation during the dissolution process. In the current study, in order to enhance dissolution and eliminate gelation of LF, a supramolecular coamorphous system of LF-baicalein (BAI) (molar ratio, 1∶1) was prepared by rotary evaporation and characterized by PLM, PXRD, DSC and FTIR. Results indicated the formation of coamorphous system with a single Tg of 118 °C. Different from original LF crystal, no gelation phenomenon was observed during the dissolution of coamorphous LF-BAI. In addition, the dissolution rate of LF was increased by 2.2-fold after coamorphization. Meanwhile, the dissolution rate of the co-former BAI was also enhanced by more than 25.4-fold. Stability test showed that the prepared coamorphous system had a good physical stability for at least 90 days under 25 °C/ 60%RH and 40 °C /75%RH conditions.

Hypereosinophilia (HE) is a kind of hematology disorder affecting multiple organs. Multiple studies demonstrated that HE was correlated with ischemic stroke, and it could be a rare and reversible cause for ischemic stroke. Therefore, more and more concerns have been concentrated by neurologists in recent years. Based on the research data, the definition, typical characteristics, possible mechanism, diagnosis and treatment principles of HE related ischemic stroke were summarized systematically, in order to provide possible personalized treatment strategies for this disease.

OBJECTIVE: To study the prevalence and clinical characteristics of decreased myocardial blood flow (MBF) quantified by dynamic computed tomography (CT) myocardial perfusion imaging (MPI) in symptomatic patients without in-stent restenosis. MATERIALS AND METHODS: Thirty-seven (mean age, 71.3 ± 10 years; age range, 48–88 years; 31 males, 6 females) consecutive symptomatic patients with patent coronary stents and without obstructive de novo lesions were prospectively enrolled to undergo dynamic CT-MPI using a third-generation dual-source CT scanner. The shuttle-mode acquisition technique was used to image the complete left ventricle. A bolus of contrast media (50 mL; iopromide, 370 mg iodine/mL) was injected into the antecubital vein at a rate of 6 mL/s, followed by a 40-mL saline flush. The mean MBF value and other quantitative parameters were measured for each segment of both stented-vessel territories and reference territories. The MBFratio was defined as the ratio of the mean MBF value of the whole stent-vessel territory to that of the whole reference territory. An MBFratio of 0.85 was used as the cut-off value to distinguish hypoperfused from non-hypoperfused segments. RESULTS: A total of 629 segments of 37 patients were ultimately included for analysis. The mean effective dose of dynamic CT-MPI was 3.1 ± 1.2 mSv (range, 1.7–6.3 mSv). The mean MBF of stent-vessel territories was decreased in 19 lesions and 81 segments. Compared to stent-vessel territories without hypoperfusion, the mean MBF and myocardial blood volume were markedly lower in hypoperfused stent-vessel territories (77.5 ± 16.6 mL/100 mL/min vs. 140.4 ± 24.1 mL/100 mL/min [p < 0.001] and 6.4 ± 3.7 mL/100 mL vs. 11.5 ± 4 mL/100 mL [p < 0.001, respectively]). Myocardial hypoperfusion in stent-vessel territories was present in 48.6% (18/37) of patients. None of clinical parameters differed statistically significantly between hypoperfusion and non-hypoperfusion subgroups. CONCLUSION: Decreased MBF is commonly present in patients who are symptomatic after percutaneous coronary intervention, despite patent stents and can be detected by dynamic CT-MPI using a low radiation dose.
Angiography ; Blood Volume ; Contrast Media ; Coronary Artery Disease ; Heart Ventricles ; Humans ; Male ; Multidetector Computed Tomography ; Myocardial Perfusion Imaging ; Percutaneous Coronary Intervention ; Prevalence ; Prospective Studies ; Stents ; Veins

Objective:To explore the feasibility in evaluating segmental extracellular volume (ECV) using dual-layer spectral detector CT in patients with heart failure with various percentages of delayed hyper-enhanced volume, using MRI as a reference.Methods:Twenty-seven patients with heart failure in Peking Union Medical College Hospital were prospectively enrolled in this study from July 2019 to January 2021. All the patients underwent both CT late iodine enhancement and MR late gadolinium enhancement imaging within a week. According to percentages of hyper-enhanced volume on cardiac MR image, myocardial segments were classified into 3 groups: 0-4% (group A), 5%-49% (group B) and 50%-100% (group C). ECV images were independently observed by 2 experienced radiologists. The correlation and agreement between CT-ECV and MRI-ECV for the whole myocardial assessment and for the segmental assessment were evaluated using Spearman correlation and Bland-Altman analysis. Inter-observer agreement was assessed using the ICC.Results:Of the 27 patients, 432 segments were analyzed, with 199 segments in group A, 151 segments in group B and 82 segments in group C. In the whole myocardial analysis, the CT-ECV and MRI-ECV were 32.25% (28.04%, 34.28%) and 32.27% (28.35%, 34.77%), respectively. A good correlation was found between CT-ECV and MRI-ECV ( r=0.969, P<0.001). Bland-Altman analysis between CT-ECV and MRI-ECV showed a small bias (0.4%), with 95% limits of agreement of -6.9% to 7.8%. as for the segmental myocardial assessment, the CT-ECV was 28.23% (26.18%, 29.92%) for group A, 33.29% (30.16%, 35.96%) for group B and 40.22% (34.06%, 46.70%) for group C. There was statistically significant difference in ECV among three groups (all P<0.001). Good correlations between CT-ECV and MRI-ECV were found in group A ( r=0.614, P<0.001), group B ( r=0.852, P<0.001) and group C ( r=0.953, P<0.001). Bland-Altman analysis between CT-ECV and MRI-ECV showed a small bias 2.0% (95% limits of agreement:-17.6%-21.6%) in group A, a small bias -0.4% (95% limits of agreement: -13.8%-12.9%) in group B and a small bias -1.8% (95% limits of agreement: -17.4%-13.9%) in group C. The ICC values between 2 observers were 0.877 and 0.945 on CT-ECV and MRI-ECV, respectively. Conclusions:The larger percentage of hyper-enhanced volume on cardiac MR image, the stronger correlation are between the CT-ECV and MRI-ECV. CT-ECV may be taken as an alternative tool for quantitative evaluation of myocardial tissue in patients with heart failure.