Sequential delivery of PD-1/PD-L1 blockade peptide and IDO inhibitor for immunosuppressive microenvironment remodeling via an MMP-2 responsive dual-targeting liposome

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

Management and prognosis of extremely preterm infants with gestational age ≤25+6 weeks / 中华儿科杂志

Objective: To investigate the outcomes including major complications and prognosis of extremely preterm infants with gestational age ≤25+6 weeks. Methods: The cross-sectional study enrolled 233 extremely preterm infants with gestational age ≤25+6 weeks who were admitted to the Department of Neonatology of Shenzhen Maternity and Child Healthcare Hospital from January 2015 to December 2021. The clinical data including perinatal factors, treatments, complications, and prognosis were extracted and analyzed. These extremely preterm infants were also grouped according to gestational age and year of admission to further analyze their survival rate, major complications, causes of death, and long-term outcomes. The comparisons between the groups were performed with Chi-square test and Kruskal-Wallis. Results: Among these 233 extremely preterm infants, 134 (57.5%) were males and 99 (42.5%) females. The gestational age was (24.6±0.9) weeks, the birth weight was 710.0 (605.0,784.5) g, and the overall survival rate was 61.8% (144/233). Among the surviving extremely preterm infants, the earliest gestational age was 22+2 weeks and the lowest birth weight was 390 g. There were 17.6% (41/233) of extremely preterm infants had treatment withdrawn and were discharged in line with the will of guardians. Among the rest 192 extremely preterm infants managed with aggressive treatments, 14 (7.3%) died in hospital and 34 (17.7%) had treatment withdrawn later due to severe complications. Of the 192 extremely preterm infants, 144 (75.0%) survived, and the survival rate increased year by year (χ2=26.28, P<0.001) while the mortality decreased year by year (χ2=14.09, P=0.027). Among the survivors, 20.8%(30/144) had no major complications, and the incidence of complications was also negatively related with the gestational age (χ2=7.24, P=0.044), and the length of invasive ventilation was negatively related to the gestational age (χ2=29.14, P<0.001). In the group of less than 23+6 weeks, all extremely preterm infants had one or more major complications. The follow-up were completed in 122 infants and revealed that delayed motor development, language retardation, and hearing and vision impairment accounted for 17.2% (21/122), 8.2% (10/122) and 17.2% (21/122), respectively. Conclusions: Extremely preterm infants with gestational age ≤25+6 weeks are difficult to treat, but the survival rate of infants undergoing aggressive treatments increases year by year. Although the prevalence of major complications is still high, most extremely preterm infants have acceptable prognosis during follow-up.

Screening and influencing factors of spine problems of children and adolescents aged 6-18 years / 公共卫生与预防医学

Objective To analyze the screening results of spinal problems in children and adolescents aged 6-18 years and the influencing factors of scoliosis to provide reference for the prevention of spinal problems in children and adolescents. Methods Stratified cluster random sampling was used to screen the prevalence of scoliosis among kindergarten to senior high school students in Shiyan city, and a questionnaire survey was conducted among subjects or parents. Multivariate logistic regression was used to analyze the risk factors affecting the occurrence of scoliosis. Results A total of 1 674 children and adolescents were investigated, and 113 cases of scoliosis were detected, with a detection rate of 6.75%. The probability of scoliosis was 1.92% (13/678), 5.35% (28/523) and 17.76% (72/473) in elementary school, junior high school and senior high school students, respectively. The detection rate of scoliosis gradually increased with the increase of education level (χ2 for trend = 5.272, P 12 h (63.72%), daily electronic product use time > 2 h (67.26%), high physical activity > 1 time/d (42.48%) in the past 7 d, and daily outdoor activity time ≤ 2 h (62.83%) were higher than those in the group without scoliosis (P 12 hours (OR=3.258 , 95% CI: 2.562-11.247), daily electronic product use time>2 hours (OR=2.619, 95% CI: 1.935-5.508) , Heavy physical activity in the past 7 days (OR=1.724, 95% CI: 1.347-2.966) , Daily outdoor activity ≤2 h（OR=1.830，95% CI: 1.463-3.103）is a risk factor for scoliosis in children and adolescents (P<0.05). Conclusions The occurrence of scoliosis in children and adolescents is related to gender, nutritional status, and learning habits, and it is necessary to strengthen the screening of high-risk groups in order to reduce the occurrence of scoliosis.

Analysis of the clinical characteristics of 8 cases of spontaneous intracranial hypotension / 中华全科医师杂志

Objective:To analyze the clinical characteristics of patients with spontaneous low intracranial pressure (SIH).Methods:The study is a retrospective series. The clinical data of patients with SIH who visited Beijing Hospital from May 2017 to March 2022, including gender, age, symptoms, signs, imaging findings, treatment and outcome, were collected and their clinical characteristics were analyzed.Results:Finally, 8 patients with SIH, 6 females and 2 males, aged (33.5±7.3) years, were included. There were 6 cases of acute onset, 1 case of subacute onset, and 1 case of chronic onset. Four cases had pre-onset triggers, 3 cases were exertional and 1 case was exercise. All 8 cases had orthostatic headache. Three cases were accompanied by neck pain. Six cases were accompanied by autonomic dysfunction, 1 case with blurred vision and neck resistance, and 1 case with tinnitus in both ears. There were no obvious abnormalities in blood routine, liver and kidney function, electrolytes, and coagulation function in 8 cases. The results of the lumbar puncture showed that the cerebrospinal fluid pressure was≤60 mmH 2O(1 mmH 2O=0.009 8 kPa) in 7 cases, and 2 cases were so low that they were undetectable. One patient had normal cerebrospinal fluid pressure (90 mmH 2O). The routine results of cerebrospinal fluid showed 4 cases of an increased number of red blood cells and 2 cases of leukocytosis. The biochemical results of cerebrospinal fluid in all 8 cases were normal. All 8 patients underwent non-contrast MRI scan of the head, and 6 cases found abnormalities, including 2 cases of subdural hematoma, 1 case of subarachnoid hemorrhage, 1 case of brain tissue sinking, and 3 cases of intracranial venous sinus dilation (including 1 case with subdural hematoma). All 8 patients underwent MRI enhancement scan of the head, and 5 patients showed diffuse dural enhancement. Three patients underwent digital subtraction angiography myelogram and computed tomography myelogram, and 2 cases found dural cerebrospinal fluid leakage. One patient underwent magnetic resonance water imaging and no cerebrospinal fluid leakage was found. Eight patients were followed up for 38.5 (10.3, 63.0) months, after conservative treatment, 6 cases of headache relief or disappearance, 1 case relapsed and was admitted 1 week after discharge, non-targeted epidural blood patching (EBP) did not relapse, 1 case underwent non-targeted EBP after conservative treatment failure, headache relief, recurrence after 2 months, thoracic spine 3-4 space targeted EBP, headache disappeared, did not recur. Conclusions:The present study indicate that SIH prevalence in young age is common, the main symptom is orthostatic headache, accommodated with multiple clinical symptoms with various imaging abnormalities. Most patients with SIH can be treated conservatively, if the effect is not good, non-targeted or targeted EBP is feasible.

Risk factors for unfavorable outcomes after recanalization of large vessel occlusion in patients with acute ischemic stroke / 中华全科医师杂志

Objective:To analyze risk factors for unfavorable outcomes after recanalization of large vessel occlusion (LVO) in patients with acute ischemic stroke (AIS).Methods:Patients with AIS-LVO who underwent recanalization treatment (including intravenous thrombolysis and endovascular intervention) at the Stroke Unit of Beijing Hospital from August 2018 to January 2022 were consecutively enrolled. According to the modified Rankin Scale (mRS) at 90-day follow-up after recanalization treatment, participants were classified as unfavorable outcomes (mRS>2) and favorable outcomes (mRS≤2). Baseline clinical data of enrolled patients was collected, and step-wise multivariate logistic regression analysis was used to identify independent risk factors for unfavorable outcomes after recanalization in AIS-LVO patients.Results:A total of 212 AIS-LVO patients were enrolled, including 86 females (41.35%), with an average age of 72.9 years. There were 75 patients in the favorable outcome group and 137 patients in the unfavorable outcome group. Compared with the favorable outcome group, the unfavorable outcome group had a higher average age, a higher proportion of females and patients with atrial fibrillation, higher baseline NIHSS, higher systolic blood pressure, and higher blood creatinine and D-dimer levels (all P<0.05). After adjusting for age and atrial fibrillation as confounding factors, multivariate logistic regression analysis showed that female ( OR=2.859, 95% CI: 1.202-6.799, P=0.018), higher baseline NIHSS ( OR=14.417, 95% CI: 6.269-33.158, P<0.001), higher pre-treatment systolic blood pressure ( OR=1.034, 95% CI: 1.015-1.054, P=0.001), higher emergency blood creatinine level ( OR=1.378, 95% CI: 1.105-1.719, P=0.005), and higher D-dimer level ( OR=3.594, 95% CI: 1.290-10.014, P=0.014) were independent risk factors for unfavorable outcomes after recanalization treatment in patients with AIS-LVO. Conclusion:Female, higher NIHSS, higher systolic blood pressure, higher blood creatinine level and D-dimer level are independent risk factors for unfavorable functional outcomes at 90 days after recanalization treatment of large vessel occlusion in patients with acute ischemic stroke.

Long-term follow-up results and risk factors of bleeding among very elderly patients with non-valvular atrial fibrillation / 中华全科医师杂志

Objective:To investigate the long-term follow-up results and the risk factors of bleeding among very elderly patients with non-valvular atrial fibrillation (NVAF).Methods:A total of 177 patients with NVAF admitted in Beijing Hospital from January 2016 to July 2016 were enrolled in the study, including 107 very elderly patients (aged≥80 years) and 70 elderly patients (aged 65-80 years). The demographic information, comorbid diseases, lifestyles, antithrombotic therapy, thromboembolism risks, bleeding risks, and medical history were documented. Patients were followed up for 5 years and the events of death, thromboembolism, bleeding and major bleeding were recorded.Results:There was no significant difference in the incidence of thromboembolic events between the two groups (15.9%(17/107) vs. 14.3%(10/70), P>0.05). The proportions of bleeding events and severe bleeding events in the very elderly group were higher than those in the elderly group (45.8%(49/107) vs.10.0%(7/70), 14.0%(15/107) vs. 1.4%(1/70), both P<0.05). According to the bleeding events during follow-up, very elderly patients were divided into bleeding group ( n=49) and non-bleeding group ( n=58). Compared with the non-bleeding group, patients in the bleeding group had an older age, a higher proportion of chronic cardiac insufficiency, chronic kidney disease, malignant tumor, bleeding history and higher bleeding risk score (HAS-BLED score) (all P<0.05). Multivariate logistic regression model analysis showed that age, HAS-BLED score, history of bleeding, and complicated malignant tumor were independent risk factors for bleeding events in very elderly patients with NVAF (all P<0.05). Conclusions:Very elderly patients with NVAF have a similar risk of thromboembolism compared with the younger elderly, but have significantly higher risk of the bleeding and major bleeding. Age, HAS-BLED score, bleeding history, and malignant tumor are independent risk factors for bleeding events in very elderly NVAF patients.

Effects and Mechanisms of Combined Application of Molecular Targeted Drugs on Proliferation of Hepatocellular Carcinoma SK-Hep-1 Cells / 肿瘤防治研究

Objective To study the effects and mechanisms of molecular targeted drug combination on multi-driven proliferation hepatocellular carcinoma SK-Hep-1 cells. Methods Four molecular targeted drugs (HG6-64-1, Dasatinib, Crizotinib, and Sunitinib) were used to treat SK-Hep-1 cells, and the monophasic kinetic analysis curve and two-phase analysis curve were drawn. Western blot analysis was used to detect the effects of the above drugs on key signaling pathways in SK-Hep-1 cells. MTT assay was used to detect the effects of the above drugs and their combination on the proliferation of SK-Hep-1 cells. Results Compared with the monophasic kinetic analysis curve, the biphase analysis curve could better fit the effects of molecular targeted drugs on SK-Hep-1 cells, which predicted that the combination of HG6-64-1, Dasatinib, and MK-2206 could effectively inhibit the proliferation of SK-Hep-1 cells. Conclusion Two-phase kinetic analysis can quantitatively describe the response of multi-driven proliferation hepatocellular carcinoma SK-Hep-1 cells to molecular targeted therapy. The combination of HG6-64-1, Dasatinib, and MK-2206 is a potential drug combination for the treatment of hepatocellular carcinoma.

Efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit / 中华神经科杂志

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Effects of cinepazide maleate injection on blood pressure in patients with acute ischemic stroke and hypertension / 中华内科杂志

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Research Progress of Biodegradable Vascular Stent / 中国医疗器械杂志

Biodegradable vascular stents have better biocompatibility than drug-eluting stents. The blood vessels are rebuilt and degraded after normal physiological functions are restored. Due to it will not stay in the body for a long time and the patients don't need taking anti-rejection drugs all the time, it becomes the focus of attention in the treatment of coronary heart disease. This article introduced the development history of biodegradable stents and reviewed the research status of several different materials of vascular stents (animals or humans)

The application values of MR quantitative susceptibility mapping in differentiation between knee meniscus degeneration and tear / 中华放射学杂志

Objective:To evaluate the feasibility and the application values of quantitative susceptibility mapping (QSM) for the assessment of meniscal injury and in distinguishing meniscus degeneration and tears.Methods:The clinical and imaging data of 70 patients suspected of meniscus injury and scheduled for arthroscopy in Shandong Medical Imaging Research Institute, Cheeloo College of Medicine, Shandong University from November 2019 to June 2020 were analyzed retrospectively. Thirty age-and sex-matched healthy subjects were also examined as controls. All subjects received knee joint QSM and routine MR imaging. According to the results of arthroscopy, the patients was divided into meniscus degeneration and meniscus tear groups, respectively. The conventional MR was evaluated by two radiologists. The meniscus injury area was delineated on the original QSM magnitude images (the central area of the posterior corner of the lateral meniscus was selected in the healthy controls) and mapped to the corresponding QSM maps, and the magnetic susceptibility values were measured. Kruskal-Wallis H test was used to analyze the magnetic sensitivity values of meniscal degeneration, meniscal tear and healthy control groups; and Bonferroni was used to correct the pairwise comparison. ROC curve was established to evaluate the threshold and efficacy of magnetic susceptibility value in the diagnosis of meniscal tear. The results were compared with those of conventional MRI. Results:The magnetic susceptibility values of meniscus of healthy controls, meniscal degeneration and meniscal tear groups were (0.035±0.016)ppm, -0.031(-0.040,-0.005)ppm, and(-0.122±0.115)ppm, respectively, with significant difference found among the three groups (χ2=44.419, P<0.05). The magnetic susceptibility values of meniscus of healthy controls was significantly higher than those of meniscus degeneration patients and meniscus tear patients (χ2=-23.843, -48.253, P<0.05). The magnetic susceptibility values of meniscus of meniscus tear group was significant lower than those of meniscus degeneration group (χ2=-24.410, P<0.05). Taking magnetic susceptibility values of -0.062 5 ppm as threshold, the area under the ROC curve for the diagnosis of meniscal tears was 0.949, with the sensitivity as 87% and the specificity as 100%. The sensitivity and specificity of conventional MRI in the diagnosis of meniscal tears were 86.8% and 87.5%, respectively. Conclusion:QSM can quantitatively evaluate meniscus injury and can be used as an effective supplement method to conventional MRI, which is helpful to improve the diagnosis of meniscus tear.

Pirfenidone suppressing esophageal stent-related restenosis after stent placement: an animal experimental study / 中华放射学杂志

Objective:To investigate the preventive efficacy of pirfenidone in esophageal stent-related restenosis and the related underlying mechanisms.Methods:Twenty-four rats underwent esophageal stent placement were included in this study. The rats were randomly assigned to three groups, with 8 rats in each group. The three groups were set to receive placebo, 150 mg/kg pirfenidone and 300 mg/kg pirfenidone daily by oral administration for 28 days, respectively. Twenty-eight days after stent placement, the stented esophagi were harvested for histological examinations. The number of epithelial layers, the thickness of submucosal fibrosis, the percentage of granulation tissue area, the degree of inflammatory cell infiltration, the degree of collagen deposition, and the α-SMA staining scores were evaluated. One-way ANOVA was performed for the statistical comparison of the number of epithelial layers, the degree of inflammatory cell infiltration, the degree of collagen deposition and the α-SMA staining scores among these three groups. The Kruskal-Wallis H test was used for comparison of the thickness of submucosal fibrosis and the percentage of granulation tissue area among the three groups. Results:Gross pathological findings showed that both pirfenidone groups had significantly less luminal fibrotic tissue formation and restenosis than placebo group. The percentage of granulation tissue areas in placebo group, 150 mg/kg and 300 mg/kg pirfenidone groups were 57.23%±25.68%, 21.80%±6.65% and 12.18%±6.37%, respectively. Both pirfenidone groups showed significantly less granulation tissue areas than placebo group ( P<0.01). The degree of inflammatory cell infiltration, the degree of collagen deposition and the α-SMA staining scores were 3.28±0.55, 3.38±0.63 and 2.75±0.38 in placebo group, 2.30±0.46, 2.36±0.58 and 2.00±0.42 in 150 mg/kg pirfenidone group, and 1.86±0.38, 1.91±0.41 and 1.57±0.28 in 300 mg/kg pirfenidone group, respectively. Both pirfenidone groups showed significantly less inflammatory cell infiltration, collagen deposition and α-SMA staining scores than placebo group ( P<0.01). Conclusion:Pirfenidone can suppress esophageal stent-related restenosis in rats by significantly inhibiting inflammation, myofibroblast activation and proliferation, and fibrotic tissue formation.

Application of diffusion weighted imaging with background suppression in evaluating the injury of lower limb nerves in patients with Guillain-Barre syndrome / 中华放射学杂志

Objective:To evaluate the value of DWI with background suppression (DWIBS) in evaluating the injury of the low limb nerves in patients with Guillain-Barre syndrome (GBS).Methods:The clinical and imaging data of 30 patients with GBS and 30 healthy volunteers matched with their age and gender in Zibo Central Hospital from January 2018 to December 2019 were analyzed retrospectively. All patients received lower limb nerve electrophysiological examination and all subjects received lower limb nerve DWIBS examination one week later. The display of tibial nerve and common peroneal nerve after DWIBS image reconstruction in normal volunteers and GBS patients was scored by two senior radiologists. Kappa consistency test was used to analyze the consistency of the two senior radiologists′ scores. One-way ANOVA was used to compare the motor nerve conduction velocity (MCV) and motor nerve conduction amplitudes of tibial nerve and common peroneal nerve in patients with GBS among different DWIBS scores. Spearman correlation analysis was used to evaluate the correlation between DWIBS tibial nerve and common peroneal nerve scores and electrophysiological parameters in patients with GBS.Results:In the DWIBS images of 30 healthy volunteers, 60 tibial nerves and common peroneal nerves showed clear, sharp edges, good signal intensity, uniformity, and the scores were 4. The consistency between the two radiologists was good (Kappa value=1.0). In the 60 tibial nerves and common peroneal nerves of 30 GBS patients, 53 tibial nerves and 52 common peroneal nerves showed abnormal changes in varying degrees, including blurred edges, distortions, difficulty in recognition, and weakened signal strength, etc. The consistency between the two readers was good (Kappa value=0.879,0.863,respectively.).With the decrease of DWIBS score, the MCV and motor nerve conduction amplitude values of tibial nerves and common peroneal nervesin GBS patients decreased, and the differences between the score groups were statistically significant ( P<0.01). The scores of tibial nerves and common peroneal nerves in DWIBS were positively correlated with MCV ( r=0.83, 0.84, respectively, P<0.05) and motor nerve conduction amplitude ( r=0.81, 0.79, respectively, P<0.05). Conclusion:DWIBS could provide a three dimensional visualization of tibial nerves and common peroneal nerves, and evaluate the disorders of peripheral nerves in patients with GBS. There has correlation between the scores of tibial nerves and common peroneal nerves in DWIBS with electrophysiology parameters.

Preparation and targeting capability of corona forming in human ovarian plasma / 药学学报

After entering the physiological environment, proteins and other biomolecules bind to the nanoparticles' surface, called protein corona. The corona establishes a new bio-interface that affects its physicochemical properties and biological behaviors. Variations in types and contents of human plasma proteins during the different physiological states can substantially change the composition and effects of the corona. With folic acid (FA)-modified polylactic acid-polyglycolic acid copolymer (PLGA) nanoparticles, the formation of protein coronas and their influence on the targeting capability are studied in healthy and ovarian human plasma. All human plasma samples were collected at the Peking University Third Hospital and this study protocol has been approved by Peking University Third Hospital Medical Science Research Ethics Committee (2019-409-1). Dynamic light scattering measurements demonstrated a 10-40 nm increase in their size distributions and a 30 mV decreased in their absolute zeta-potential since protein corona-coated PLGA-PEG and PLGA-FA were formed. The SDS-PAGE analysis showed the composition of the protein coronas from ovarian and healthy plasma in PLGA-FA were markedly distinct, particularly for proteins with molecular weight of 45, 110 and >180 kDa. Flow cytometry indicated that the absorption of ovarian plasma in PLGA-FA led to a lower cellular uptake by SKOV3 cells. Our results suggest that in vitro formed ovarian plasma protein corona could shield targeting molecules and reduced receptor-mediated internalization. The results of this pilot study will provide evidence of the effectiveness of active targeting nanoparticles under pathologic conditions. Additionally, the protein corona in different diseases is emerging as a key point; thus, a comprehensive understanding could accelerate clinical translation of functionalized nanoparticles.

An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis

Localized delivery, comparing to systemic drug administration, offers a unique alternative to enhance efficacy, lower dosage, and minimize systemic tissue toxicity by releasing therapeutics locally and specifically to the site of interests. Herein, a localized drug delivery platform ("plum‒pudding" structure) with controlled release and long-acting features is developed through an injectable hydrogel ("pudding") crosslinked

Percutaneous intranodal lymphography: diagnostic and therapeutic effect for patients with chylous leakage / 中华放射学杂志

Objective:To evaluate the diagnostic and therapeutic effect of percutaneous intranodal lymphography in patient with chylous leakage.Methods:The clinical data of percutaneous intranodal lymphography in patients with chylous leakage from January 2019 to November 2019 in Cancer Hospital Chinese Academy of Medical Sciences were retrospectively analyzed. A total of 8 patients (5 males and 3 females, median age 64 years old) were enrolled. Four patients were iatrogenic chylothorax, 3 patients iatrogenic chyloperitoneum, and 1 patient chyloperitoneum with unknown cause. All 8 patients were received inguinal lymph nodes puncture under ultrasound guidance, and contrast agent iodinated oil was injected for lymphography. The procedure complications were recorded and the follow-up data were collected for efficacy assessment.Results:The percutaneous intranodal lymphography was successfully performed in all patients (8/8). The median amount of iodinated oil used was 17.5 ml; the median operation time was 88 min, without complications found during the procedure. The results of percutaneous intranodal lymphography was positive in 5/8 cases, of which chylothorax and chyloperitoneum was 4/4 and 1/4, respectively. Four cases with chylothorax showed contrast extravasation at different level of thoracic duct, and 1 case after pancreatic cancer resection showed contrast extravasation at L3-4 level. The chylous leakage was treated in 5 patients (5/8) during and resolved after percutaneous intranodal lymphography, with 3 chylothorax and 2 chyloperitoneum cases, respectively.Conclusion:Percutaneous intranodal lymphography is a safe and effective lymphography method for the diagnosis of chylous leakage, and also has application values in the treatment of chylous leakage.

Feasibility of prenatal MRI in the diagnosis of fetal external ear developmental malformation / 中华放射学杂志

Objective:To discuss the feasibility of prenatal MRI in evaluating fetal auricle developmental malformation and atresia of external auditory canal.Methods:Fifteen pregnant women (aged from 22 to 40 years old, mean age 31.3±5.2 years old) with fetal external ear developmental malformation suspected by ultrasound underwent MR scanning between November 2017 and May 2019. All of them were singleton. The gestational age ranged from 23 weeks to 35 weeks, with an average of (27.5±3.5) weeks. The sensitivity, specificity and accuracy of MRI and ultrasound in the diagnosis of fetal auricle malformation and atresia of external auditory canal were calculated and compared, using postnatal follow-up as the gold standard. Fisher exact test was used to compare the efficacy of MRI and ultrasound in diagnosing atresia of external auditory canal.Results:A total of 30 fetal external ears were detected in 15 fetuses, without auricle absence. Totally 19 external ears with developmental malformation were confirmed by postnatal follow-up, including 19 ears with auricle malformation and 15 ears with external auditory canal atresia. The accuracy of MRI and ultrasound in the diagnosis of auricle malformation was both 100% (19/19). For the diagnosis of external auditory canal atresia, the sensitivity, specificity and accuracy of MRI and ultrasound were 93.3% (14/15), 75.0% (3/4), 89.5% (17/19) and 33.3% (5/15), 25.0% (1/4), 31.6% (6/19), respectively. The sensitivity and accuracy of MRI in the diagnosis of atresia of external auditory canal were significantly higher than those of ultrasound, with statistically significant difference ( P=0.004, 0.001). Conclusion:MRI plays an important role in the diagnosis of fetal external ear developmental malformation, which can be used as an effective supplement to ultrasound, especially for the diagnosis of external auditory atresia.

Evaluation of the neurodevelopment outcome of prenatally diagnosed periventricular pseudocysts using MRI / 中华放射学杂志

Objective:To evaluate alterations of periventricular pseudocysts (PVPC) on MRI before and after birth, and to assess the prognosis.Methods:We retrospectively analyzed the data of 67 cases that were diagnosed with PVPC on prenatal MRI, of which 24 cases were lost to follow-up, 2 died after birth. A total of 41 surviving fetuses were included in this prognosis study. The gestational ages in this group were between 23 and 39 weeks, with an average of (33±3) weeks.All the subjects underwent brain MRI examinations and Gesell Developmental Scale (GDS) testing between 0-3 years of age. According to the location of cysts and with or without other intracranial and extracranial malformations (dilated ventricles orcerebella medulla, hypoxic-ischemic encephalopathy, TORCH virus infection, corporal hypoplasia, chromosomal malformations and nodular sclerosis) , the patients were divided into four groups: isolated connatal cysts, connatal cysts with additional findings,isolated subependymal pseudocysts, and subependymal pseudocysts with additional findings.The MR images were independently reviewed by two radiologists blinded to the clinical information. Intraclass correlation efficient (ICC) was used to analyze the consistency between the two reviewers.Chi-square test was used to compare the location of cysts (single/bilateral), the number of cyst cavities (single/multi-chamber), and other abnormalities in the connatal cyst group and subependymal cyst group. The mean anteroposterior diameter and mean height of cysts between the connatal cyst group and subependymal cyst group were compared by independent sample t-test.The ANOVA test was used to compare the differences in GDS outcomes among the groups. Multiple comparisons were conducted using the LSD test. Results:Inter-observer agreements between the two radiologists were good for the collected data (all ICC>0.75). Eleven isolated connatal cysts and 7 connatal cysts with additional findings became smaller or disappeared, and all had good prognosis. Of the 14 isolated subependymal cysts, 12 became smaller or disappeared, 2 had no change in size, and 13 had good prognosis. The subependymal cysts with additional findings group included 9 cases: 6 became smaller or disappeared, only 3 showed no apparent changes, and 7 had an abnormal outcome. Subependymal cysts with additional findings were significantly reduced and patients demonstrated significant differences compared with the those with isolated subependymal cysts in the development quotients (DQ) of adaptability, large movements, fine movements, personal social interaction, and language DQ ( P all<0.05). DQ between patients with isolated connatal cysts and isolated subependymal cysts was comparable ( P all>0.05). When associated with additional findings, connatal cysts and subependymal cysts could induce significant different DQ outcome ( P all<0.05). Conclusions:Isolated PVPC usually become smaller or disappeared and have a benign presentation after birth, whereas patients with subependymal cysts with additional findings usually have a poor prognosis. Connatal cysts usually have a good prognosis.

Characteristics of oral methicillin-resistant Staphylococcus epidermidis isolated from dental plaque / 国际口腔科学杂志·英文版

The oral microbial community is widely regarded as a latent reservoir of antibiotic resistance genes. This study assessed the molecular epidemiology, susceptibility profile, and resistance mechanisms of 35 methicillin-resistant Staphylococcus epidermidis (MRSE) strains isolated from the dental plaque of a healthy human population. Broth microdilution minimum inhibitory concentrations (MICs) revealed that all the isolates were nonsusceptible to oxacillin and penicillin G. Most of them were also resistant to trimethoprim (65.7%) and erythromycin (54.3%). The resistance to multiple antibiotics was found to be largely due to the acquisition of plasmid-borne genes. The mecA and dfrA genes were found in all the isolates, mostly dfrG (80%), aacA-aphD (20%), aadD (28.6%), aphA3 (22.9%), msrA (5.7%), and the ermC gene (14.3%). Classical mutational mechanisms found in these isolates were mainly efflux pumps such as qacA (31.4%), qacC (25.7%), tetK (17.1%), and norA (8.6%). Multilocus sequence type analysis revealed that sequence type 59 (ST59) strains comprised 71.43% of the typed isolates, and the eBURST algorithm clustered STs into the clonal complex 2-II(CC2-II). The staphyloccoccal cassette chromosome mec (SCCmec) type results showed that 25 (71.43%) were assigned to type IV. Moreover, 88.66% of the isolates were found to harbor six or more biofilm-associated genes. The aap, atlE, embp, sdrF, and IS256 genes were detected in all 35 isolates. This research demonstrates that biofilm-positive multiple-antibiotic-resistant ST59-SCCmec IV S. epidermidis strains exist in the dental plaque of healthy people and may be a potential risk for the transmission of antibiotic resistance.

Efficacy of revascularization in oldest-old patients with acute ischemic stroke / 中华全科医师杂志

Objective@#To analyze the efficacy of revascularization in oldest-old patients with acute ischemic stroke (AIS).@*Methods@#The clinical data of AIS patients receiving recanalization therapy in Beijing Hospital from January 2010 to July 2018 were retrospectively reviewed. Among 141 patients, there were 34 cases aged ≥80 years (oldest-old group) and 107 cases aged<80 years (old group).The clinical characteristics and outcomes of two groups were analyzed and compared.@*Results@#The proportions of patients with atrial fibrillation and coronary heart disease in oldest-old group were high than those in the old group [61.8% (21/34) vs. 33.6%(36/107), χ2=8.47, P<0.01; 58.8% (20/34) vs. 32.7% (35/107), P<0.01, respectively]; while there were no significant differences in other risk factors between two groups (P>0.05). The National Institute of Health Stroke Scale Score (NIHSS) was higher in the oldest-old group than that in old group [16 (13,21) vs. 11 (6,16), Z=3.74, P<0.01]. In the etiological classification, cardiogenic embolism was the main cause in the oldest-old group (58.8%, 20/34), while large artery atherosclerosis was the main cause in the old group (46.7%, 50/107, χ2=12.11, P<0.01). There were no significant differences between the two groups in the methods of recanalization [intravenous thrombolysis were 35.3% (12/34) and 48.6% (52/107); endovascular therapy were 52.9% (18/34) and 36.4% (39/107), bridging therapy were 11.8% (4/34) and 15.0% (16/107), respectively; χ2=2.93,P=0.23] and the time from onset to treatment [195(154, 269) min vs. 215 (153,280)min, Z=1.03, P>0.05]. The 3-month independent (modified Rankin score ≤2) rate was lower in the oldest-old group than that in the old group [35.3% (12/34) vs. 56.1%(60/107), χ2=4.46, P<0.05). The 3-month mortality was higher in the oldest-old group than that in the old group [29.4% (10/34) vs. 8.4%(9/107), χ2=9.76, P<0.01]. There was a tendency of increased incidence of symptomatic intracranial hemorrhage (SICH) in the oldest-old patients compared to the old patients [11.8% (4/34) vs. 7.5% (8/107), P>0.05].@*Conclusion@#The conditions of AIS patients aged ≥80 years are more serious than those of patients aged<80 years, with higher mortality and lower functional improvement rate after recanalization treatment.