Objective To observe the clinical and echocardiographic manifestations of Williams syndrome(WS).Methods Two children with WS were retrospectively enrolled,and 21 cases of WS in literature were reviewed,and clinical and echocardiographic manifestations of WS were observed.Results Clinical manifestations of 23 cases including 21 cases of"elf"face,8 cases of intellectual disability,7 cases of developmental delay,7 cases of inguinal hernia,6 cases of hypothyroidism,4 cases of hypercalcemia,3 cases of urinary system abnormalities(1 case of hydrocele,1 case of ureteral dilation and tortuosity,and 1 case of kidney stones),2 cases of behavioral abnormalities,2 cases of feeding difficulties,1 case of congenital hypertrophic pyloric stenosis,1 case of binocular esotropia,1 case of hyperbilirubinemia,and 1 case of corpus callosum dysplasia.Echocardiography showed cardiovascular malformations in all 23 cases,including 20 cases of supravalvular aortic stenosis(SVAS),18 cases of pulmonary artery stenosis(PAS)and 10 cases of other cardiovascular malformations.Conclusion WS presented multiple system abnormalities in clinic,and cardiovascular malformations,especially SVAS and PAS could often be detected with echocardiography.

Objective To observe the clinical and echocardiographic manifestations of Williams syndrome(WS).Methods Two children with WS were retrospectively enrolled,and 21 cases of WS in literature were reviewed,and clinical and echocardiographic manifestations of WS were observed.Results Clinical manifestations of 23 cases including 21 cases of"elf"face,8 cases of intellectual disability,7 cases of developmental delay,7 cases of inguinal hernia,6 cases of hypothyroidism,4 cases of hypercalcemia,3 cases of urinary system abnormalities(1 case of hydrocele,1 case of ureteral dilation and tortuosity,and 1 case of kidney stones),2 cases of behavioral abnormalities,2 cases of feeding difficulties,1 case of congenital hypertrophic pyloric stenosis,1 case of binocular esotropia,1 case of hyperbilirubinemia,and 1 case of corpus callosum dysplasia.Echocardiography showed cardiovascular malformations in all 23 cases,including 20 cases of supravalvular aortic stenosis(SVAS),18 cases of pulmonary artery stenosis(PAS)and 10 cases of other cardiovascular malformations.Conclusion WS presented multiple system abnormalities in clinic,and cardiovascular malformations,especially SVAS and PAS could often be detected with echocardiography.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Background: Excessive growth of keratinocytes is the critical event in the etiology of psoriasis.However, the underlying molecular mechanism of psoriatic keratinocyte hyperproliferation is still unclear. Objective: This study aimed to figure out the potential contributory role of S-phase kinase-associated protein 2 (SKP2) in promoting the hyperproliferation of keratinocytes in psoriasis. Methods: We analyzed microarray data (GSE41662) to investigate the gene expression of SKP2in psoriatic lesion skins compared with their adjacent non-lesional skin. Then, we further confirmed the mRNA and protein expression of SKP2 in human psoriatic skin tissues, imiquimod (IMQ)-induced psoriatic mice back skins and tumor necrosis factor α (TNF-α), interleukin (IL)-17A and IL-6-stimulated keratinocytes by using real-time quantitative polymerase chain reaction and western blot (WB). Furthermore, we explored the potential pathogenic role and its underlying cellular mechanism of SKP2 in promoting keratinocytes hyperproliferation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle detection, 5-ethynyl-2′-deoxyuridine staining and WB. Finally, we determined whether inhibition of SKP2 can effectively alleviate the keratinocytes hyperproliferation in vivo. Results: We identified that SKP2 is aberrantly upregulated in the psoriatic lesion skin and cytokines-stimulated keratinocytes. Moreover, upregulated SKP2 augments cytokines-induced keratinocytes hyperproliferation. Mechanistically, enhanced SKP2 increased the S phase ratio through inhibiting Cyclin-Dependent Kinase Inhibitor p27 (P27 Kip1) expression. Correspondingly, suppression of SKP2 with SMIP004 can significantly ease the epidermis hyperplasia in vivo. Conclusion Our results suggest that elevated SKP2 can empower keratinocytes proliferation and psoriasis-like epidermis hyperplasia via downregulation of P27 Kip1. Therefore, targeting SKP2-P27 Kip1 axis might be a promising therapeutic strategy for the treatment of psoriasis in future.

Humans ; HIV-1/genetics* ; Anti-Retroviral Agents/therapeutic use* ; Mutation/genetics* ; Treatment Failure ; HIV Infections/genetics* ; Drug Resistance, Viral/genetics* ; Anti-HIV Agents/therapeutic use* ; Genotype

Objective:To explore the effect of the application of nursing decision support information system in the continuing nursing of stroke patients in convalescent period, and to provide guidance for the information-based whole process nursing of stroke patients in convalescent period.Methods:A total of 107 stroke patients in convalescent period admitted to 4 Grade Ⅲ Level A hospitals of Beijing city from March to November 2019 were selected. The patients were divided into control group (53 cases) and test group (54 cases) by coin tossing method. The control group followed uniformly formulated discharge health education manual for post-discharge management and follow-up, while the test group received health guidance and follow-up through the nursing decision support information system. Barthel Index and MOS SF-36 were used to evaluate the activities of daily living and quality of life of the two groups of patients before intervention and 3 and 6 months after the intervention, and the results were compared.Results:There was no significant difference in Barthel Index before the intervention between the two groups( P>0.05). After 3 months of intervention, the Barthel Index ≤ 49, 50-70 and ≥ 71 in the test group were 7, 17 and 27 cases respectively, and 16, 21 and 13 cases in the control group respectively, and the difference between the two groups was statistically significant ( Z=-2.95, P<0.01). After 6 months of intervention, the Barthel Index ≤ 49, 50-70 and ≥ 71 in the test group were 7, 12 and 32 cases respectively, and 10, 15 and 25 cases in the control group respectively,and the difference between the two groups was statistically significant ( Z=-2.21, P<0.05). There was no significant difference in MOS SF-36 before the intervention between the two groups( P>0.05). After 3 and 6 months of intervention, the total score of MOS SF-36 in the test group was (50.51 ± 14.57), (57.06 ± 14.85) respectively, and that in the control group was (42.02 ± 15.48), (45.58 ± 14.97) respectively, and the differences between the two groups were statistically significant ( t=2.84, 3.23, both P<0.05). Conclusions:The application of nursing decision support information system can effectively improve the daily life ability of patients, enhance the quality of life of patients.

Polymer micelles formed by self-assembly of amphiphilic polymers are widely used in drug delivery, gene delivery and biosensors, due to their special hydrophobic core/hydrophilic shell structure and nanoscale. However, the structural stability of polymer micelles can be affected strongly by environmental factors, such as temperature, pH, shear force in the blood and interaction with non-target cells, leading to degradations and drug leakage as drug carriers. Therefore, researches on the structural integrity and in vivo distribution of micelle-based carriers are very important for evaluating their therapeutic effect and clinical feasibility. At present, fluorescence resonance energy transfer (FRET) technology has been widely used in real-time monitoring of aggregation, dissociation and distribution of polymer micelles ( in vitro and in vivo). In this review, the polymer micelles, characteristics of FRET technology, structure and properties of the FRET-polymer micelles are briefly introduced. Then, methods and mechanism for combinations of several commonly used fluorescent probes into polymer micelles structures, and progresses on the stability and distribution studies of FRET-polymer micelles ( in vitro and in vivo) as drug carriers are reviewed, and current challenges of FRET technology and future directions are discussed.
Micelles ; Drug Carriers/chemistry* ; Polymers/chemistry* ; Fluorescence Resonance Energy Transfer ; Polyethylene Glycols/chemistry*

Objective:To understand the incidence and clinical characteristics of dopamine agonist(DA) therapy-related impulse control disorders(ICDs) in prolactinoma patients.Methods:Outpatients diagnosed with prolactinoma from the Department of Endocrinology in Huashan Hospital from December 2019 to June 2020 were consecutively included and clinical data were collected. Impulse control disorders were screened with Questionnaire for Impulsive-Compulsive Disorders in Parkinson′s Disease(QUIP). Barratt Impulsiveness Scale 11(BIS-11) was used to evaluate personality construct of impulsiveness from three sub-factors . Health related quality of life was evaluated by the MOS 36-Item Short Form Health Survey(SF-36).Results:Among the 111 cases included, 40 were male and 53 were female, with an average age of(34.74±9.05) years and an average disease duration of(66.69±50.70) months. The initial prolactin level was 147.25(89.97, 470) ng/mL and the percentage of macroadenoma was 46.8%. Ninety cases received DA while 21 cases didn′t. According to the QUIP, any ICD was screened positive in 22 cases(24.7%) in the DA group and 3 cases(14.3%) in the untreated group. The attention impulsiveness scores of BIS-11 in the DA group were higher than the untreated group(23.32±3.67 vs 21.71±2.55, P=0.022). Among the ICDs positive cases in the DA group, the most common disorders were pathological gambling(40.6%) and hypersexuality(40.6%). Compared with the negative group, the non-planning impulsiveness scores of BIS-11 in the positive group were higher, while the scores of social function(69.32±24.62 vs 83.08±17.11, P=0.021), role emotional(50.00±45.72 vs 71.10±40.68, P=0.043) and mental health(55.27±22.75 vs 64.59±17.53, P=0.048) in SF-36 scale were lower in the positive group. Besides, the percentage of male(68.2% vs 38.2%, P=0.014) and initial prolactin level[470.00(130.00, 3 770.00) vs 140.29(79.50, 465.59) ng/mL, P=0.028] in the positive group were higher. Male was an independent risk factor of the presence of ICDs( OR=3.46, 95% CI 1.24-9.61, P=0.017). No significant difference was found in the type of drugs, duration, maximal or cumulative dose of treatment with DA between the two groups. Conclusion:Impulse control disorders may occur in prolactinoma patients receiving DA treatment and affect the quality of life. Endocrinologists should screen impulse control disorders in this patient set.

Polymeric hydrogels have been widely researched as drug delivery systems, wound dressings and tissue engineering scaffolds due to their unique properties such as good biocompatibility, shaping ability and similar properties to extracellular matrix. However, further development of conventional hydrogels for biomedical applications is still limited by their poor mechanical properties and self-healing properties. Currently, nanocomposite hydrogels with excellent properties and customized functions can be obtained by introducing nanoparticles into their network, and different types of nanoparticles, including carbon-based, polymer-based, inorganic-based and metal-based nanoparticle, are commonly used. Nanocomposite hydrogels incorporated with polymeric micelles can not only enhance the mechanical properties, self-healing properties and chemical properties of hydrogels, but also improve the
Biocompatible Materials ; Hydrogels ; Micelles ; Nanocomposites ; Polymers