ABSTRACT
Background@#and Purpose Intracranial vertebrobasilar atherosclerotic stenosis (IVBAS) is a major cause of posterior circulation stroke. Some patients suffer from stroke recurrence despite receiving medical treatment. This study aimed to determine the prognostic value of a new score for the posterior communicating artery and the P1 segment of the posterior cerebral artery (PCoA-P1) for predicting stroke recurrence in IVBAS. @*Methods@#We retrospectively enrolled patients with severe IVBAS (70%–99%). According to the number of stroke recurrences, patients were divided into no-recurrence, single-recurrence, and multiple-recurrences groups. We developed a new 5-point grading scale, with the PCoA-P1 score ranging from 0 to 4 based on magnetic resonance angiography, in which primary collaterals were dichotomized into good (2–4 points) and poor (0 or 1 point). Stroke recurrences after the index stroke were recorded. Patients who did not experience stroke recurrence were compared with those who experienced single or multiple stroke recurrences. @*Results@#From January 2012 to December 2019, 176 patients were enrolled, of which 116 (65.9%) had no stroke recurrence, 35 (19.9%) had a single stroke recurrence, and 25 (14.2%) had multiple stroke recurrences. Patients with single stroke recurrence (odds ratio [OR]= 4.134, 95% confidence interval [CI]=1.822–9.380, p=0.001) and multiple stroke recurrences (OR=6.894, 95% CI=2.489–19.092, p<0.001) were more likely to have poor primary collaterals than those with no stroke recurrence. @*Conclusions@#The new PCoA-P1 score appears to provide improve predictions of stroke recurrence in patients with IVBAS.
ABSTRACT
Objective:To explore the value and risk of electronic bronchoscope applied in perioperative management of children with congential tracheoesophageal fistula.Methods:Sixty-five children with congential tracheoesophageal fistula performed electronic bronchoscope examination from September 2014 to November 2020 were enrolled in this study.The results of examination and complications were analyzed.Results:Sixty-three children with congenital tracheoesophageal fistula were diagnosed by electronic bronchoscopy.The diagnosis rate was 96.92%.Fifty-four children with congenital tracheoesophageal fistula were diagnosed by esophagography.The diagnosis rate was 91.53%.Sixty-one children with congenital tracheoesophageal fistula were diagnosed by multislice spiral computed tomography.The diagnosis rate was 93.85%.Airway anatomic abnormity was found in 27 children, including three cases of nasopharyngeal soft tissue collapse, 14 cases of laryngomalacia, five cases of tracheal stenosis, nine cases of tracheobronchomalacia, and nine cases of tracheobronchial and abnormal opening of the bronchus.The incidence was 41.54%.Three children with difficult ventilator weaning were related to tracheobronchial stenosis or tracheobronchomalacia.They were gradually weaning from ventilator after a long period of mechanical ventilation and treatment.Two children with transient decrease in oxygen saturation were noticed as complication.Conclusion:Electronic bronchoscopy is a safe and effective method for the diagnosis of congenital tracheoesophageal fistula and recurrence after operation.It is of great value to the airway management after operation by early detection of respiratory anatomic abnormity.
ABSTRACT
Cancer immunotherapy has become a new generation of anti-tumor treatment, but its indications still focus on several types of tumors that are sensitive to the immune system. Therefore, effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy. Natural products are reported to have this effect on cancer immunotherapy, including cancer vaccines, immune-check points inhibitors, and adoptive immune-cells therapy. And the mechanism of that is mainly attributed to the remodeling of the tumor-immunosuppressive microenvironment, which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy. Therefore, this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism. And we found that saponins, polysaccharides, and flavonoids are mainly three categories of natural products, which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment. Besides, this review also collected the studies about nano-technology used to improve the disadvantages of natural products. All of these studies showed the great potential of natural products in cancer immunotherapy.
ABSTRACT
From January 2016 to December 2020, 6 cases of polyps in the appendix cavity with a diameter of 0.3-1.3 cm were treated by endoscopy in the Department of Gastroenterology of Beijing Friendship Hospital, Capital Medical University. All 6 cases underwent endoscopic treatment successfully, including 3 cases of en bloc endoscopic mucosal resection (EMR), 1 case of piecemeal EMR, 1 case of endoscopic submucosal dissection (ESD), and 1 case of removed by cold forceps. No complications such as bleeding, perforation, infection or acute appendicitis occurred.The wound healed well with no recurrence after re-examination in 3 cases, and 3 others were not re-examined by colonoscopy yet. The results preliminarily confirmed that endoscopic treatment of intraluminal polyps in the appendix cavity is safe and effective.
ABSTRACT
Objective:To evaluate the clinical efficacy of endoscopic treatment for early nonampullary duodenal cancer.Methods:Data of patients with early nonampullary duodenal cancer, who underwent endoscopic treatment from January 2015 to January 2021 at Beijing Friendship Hospital were retrospectively analyzed. Baseline data, endoscopic treatment methods, wound closure, pathology, the occurrence and outcome of complications of patients were studied.Results:A total of 47 patients who successfully went through endoscopic treatment were enrolled. Seventeen cases received endoscopic mucosal resection (EMR), 5 cases received endoscopic submucosal dissection (ESD), and 7 cases received ESD+EMR (hybrid ESD). Six cases were converted to hybrid ESD due to difficulty in ESD. Four cases received full-thickness resection with over-the-scope clip system (OTSC), and 8 cases received endoscopic piecemeal mucosal resection (EPMR). Among the 47 cases of early cancer, the en bloc resection rate was 83.0% (39/47), and the complete resection rate was 85.1% (40/47). Four patients (8.5%) had perforation which occurred at the duodenal descending part during the perioperative period, among whom, 2 patients (4.3%) recovered after endoscopic treatment, 2 others (4.3%) recovered after surgical intervention. There were no complications such as postoperative bleeding or infection during the perioperative period.Conclusion:Endoscopic treatment for early nonampullary duodenal cancer is safe and effective. A specific treatment plan can be selected according to the location, size and specific conditions of the lesion. For the operation of the descending part, it is necessary to be more vigilant to against the occurrence of perforation complications.
ABSTRACT
Objective:To evaluate the clinical efficacy of endoscopy for early cancer of duodenal papilla.Methods:A retrospective analysis was performed on data collected from 23 consecutive patients with early cancer of duodenal papilla, who underwent endoscopic treatment from January 2015 to January 2021 in Beijing Friendship Hospital. Baseline data, endoscopic and pathological data, occurrence and outcome of complications were studied.Results:Twenty-three patients successfully received endoscopic treatment. The maximal diameter of lesions evaluated under endoscopy was 1.90±0.83 cm. Among the 23 cases, 20 underwent endoscopic mucosal resection and 3 underwent endoscopic piecemeal mucosal resection. Delayed bleeding occurred in 5 cases (21.7%), 3 patients (13.0%) developed postoperative hyperamylasemia, 6 patients (26.1%) developed mild acute pancreatitis, and 1 patient (4.3%) had pancreatic duct stent displacement after the operation, which improved after medical or endoscopic treatment. No perforation occurred during the perioperative period. In terms of final pathology, the en bloc resection rate was 82.6% (19/23), and the complete resection rate was 78.3% (18/23). Preoperative endoscopic ultrasonography showed that 19 lesions were confined to the mucosal layer, which were all demonstrated by postoperative pathology. Four other cases were suspected to be involved in the submucosa or the end of the pancreaticobiliary duct under endoscopic ultrasonography, two of which were confined to the mucosal layer, and the other 2 cases involved the submucosal layer, so additional surgery was performed. A total of 18 patients were followed up, among whom 14 achieved complete resection of postoperative pathology, and 2 patients (14.3%, 2/14) were found to have recurrence at 12 and 51 months respectively after the treatment and did not relapse after surgical treatment and endoscopic treatment respectively. Among 4 other patients of follow-up whose pathology did not achieve complete resection, 1 had no recurrence, and the other 3 received additional surgical treatment without recurrence.Conclusion:Endoscopic treatment for early cancer of duodenal papilla is safe and effective. It is necessary to improve preoperative evaluation, stay alert to perioperative complications, and pay attention to regular postoperative endoscopic follow-up.
ABSTRACT
Objective:To analyze the results of polysomnography(PSG) in 523 children, and explore the sleep monitoring results and related influencing factors of obstructive sleep apnea hypopnea syndrome(OSAHS).Methods:The PSG monitoring results of children with OSAHS and non-OSAHS were analyzed for children aging from 0 to 16 years old, who were monitored at Sleep Medicine Center of Gansu Maternal and Child Health Hospital from January 2014 to December 2019.Results:A total of 523 children underwent PSG monitoring during the past 5 years.The male to female ratio was 1∶0.47, of which 66.9%(350/523)were children with OSAHS.The average proportion of rapid eye movement sleep was 1.95%(7.7/394). The height of non-OSAHS group was significantly higher than that of OSAHS group[(108.72±16.39)cm vs.(104.80±16.60)cm, P=0.016]. The incidence of OSAHS decreased with age( P=0.038). The apnea index, hypopnea index, apnea hypopnea index, obstructive apnea index, microarousal index, oxygen desaturation index, mean apnea time, and longest apnea time in the OSAHS group were higher than those in the non-OSAHS group( P<0.05). And the lowest oxygen saturation and the mean oxygen saturation during sleep were lower than those in the non-OSAHS group( P<0.05). Logistic regression analysis on the clinical data of OSAHS children showed that open mouth breathing and snoring at night had significant effects on children′s OSAHS, and the differences were statistically significant( P<0.05). Conclusion:PSG is of great significance for the diagnosis of OSAHS.The more severe the degree of OSAHS, the worse severe the night sleep hypoxemia.PSG should be recommended before taking any treatment for children with sleep disorders.
ABSTRACT
Objective:To investigate the predictive value of pressure ulcer score and fall score and NIHSS scale for discharge outcome in patients with acute ischemic stroke (AIS).Methods:From January 2014 and November 2018, 4 468 patients with AIS who were treated in Hebei Province Renqiu Kangjixintu Hospital were selected as the research object. According to the modified Rankin scale (mRS) score standard discharge, mRS score in 0 to 2 scores was defined as good discharge outcome, and mRS score ≥3 scores defined as bad discharge outcome. Predictive value of pressure ulcer score, fall score and NIHSS score for the discharge outcome of AIS was analyzed.Results:The score of pressure ulcer in the group with bad discharge outcome was significantly lower than that in the group with good discharge outcome: (16.96 ± 2.89) scores vs. (19.91 ± 1.71) scores, the score of fall and NIHSS in the group with bad discharge outcome were higher than that in the group with good discharge outcome, with statistical significance: (6.66 ± 1.77) scores vs. (5.21 ± 1.64) scores, (7.34 ± 5.08) scores vs. (3.15 ± 2.21) scores ( P<0.01). The cutoff values of pressure sore score, fall score and NIHSS score for predicting adverse discharge outcome were 18.5, 5.5 and 3.5 scores, respectively. The area under the curve (AUC) was 0.809, 0.731 and 0.863, respectively. The sensitivity was 86.00%, 76.200% and 78.30%, and the specificity was 64.00%, 59.50% and 80.60%. The pressure ulcer score, fall score and NIHSS score had statistical difference in predicting the adverse outcome of discharge ( P<0.01). Conclusions:The pressure ulcer score, fall score and NIHSS score have good predictive value for the discharge outcome of AIS. The lower the pressure ulcer score and the higher fall score and NIHSS score are, the higher the risk of poor discharge outcome of AIS is. Actively controlling the occurrence of pressure ulcers and falls can effectively reduce the risk of poor discharge outcome of AIS.
ABSTRACT
Objective:To investigate the clinical manifestations and characteristics of tracheobronchial foreign bodies in children, and improve the diagnosis and treatment of foreign bodies.Methods:A retrospective analysis was performed on the clinical data of children with tracheobronchial foreign bodies confirmed by fiberoptic bronchoscopy between January 2010 to December 2019.The children with tracheobronchial foreign body who were treated in the Maternal and Child Health Hospital of Gansu Province.Results:A total of 967 cases were operated by soft electronic bronchoscope, and foreign bodies were removed by means of foreign body forceps or nets.Among them, 19 cases(3 cases with subglottic foreign bodies, one with row of pins, and the rest 15 cases with foreign bodies completely wrapped by granulation)were not removed, two cases were spontaneously coughed, and 946 cases (97.8%)were removed.Bronchial foreign bodies in children were more common in boys, with the ratio of male to female being 2.14∶1.The main age of onset was 1-3 years old(88.8%). The incidence was slightly higher in rural areas than that in urban areas(46.5% in urban areas, 53.5% in rural areas). Foreign bodies were inhaled most in March and least in June.From the perspective of season, winter and spring were more than summer and autumn.The foreign body types inhaled were mainly exogenous plant foreign body, accounting for 93.0%, among which peanut(31.7%)and melon seeds(19.2%)were the most common.The duration of foreign body inhalation was up to 347 cases(35.9%)in 1-3 days.There were 501 cases(51.8%)with endoscopic endobronchial inflammation, and 196 cases of children with varying degrees of granulomatous hyperplasia, accounting for 39.1% and 20.3% of the total.The foreign body in the right bronchus accounted for 50.0% and the left bronchus for 43.7%.There were 793 cases confirmed by imaging, with a positive rate of 81.9%, and 90.9% confirmed by CT.Conclusion:About 88.8% of tracheobronchial foreign bodies occurred in 1 to 3 years of age.The occurrence of foreign bodies had obvious gender, urban-rural and seasonal distribution characteristics, and more cases were male, in rural and winter as well as spring.
ABSTRACT
Liposomes have made remarkable achievements as drug delivery vehicles in the clinic. Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs, but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents, thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy. In this study, a series of weak acid drug derivatives were designed by a simplistic one step synthesis, which could be remotely loaded into liposomes by pH gradient method. Cabazitaxel (CTX) weak acid derivatives were selected to evaluate regarding its safety profiles, pharmacodynamics, and pharmacokinetics. CTX weak acid derivative liposomes were superior to Jevtana® in terms of safety profiles, including systemic toxicity, hematological toxicity, and potential central nerve toxicity. Specifically, it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons. Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.
ABSTRACT
Background@#and Purpose Despite administration of evidence-based therapies, residual risk of stroke recurrence persists. This study aimed to evaluate the residual risk of recurrent stroke in acute ischemic stroke or transient ischemic attack (TIA) with adherence to guideline-based secondary stroke prevention and identify the risk factors of the residual risk. @*Methods@#Patients with acute ischemic stroke or TIA within 7 hours were enrolled from 169 hospitals in Third China National Stroke Registry (CNSR-III) in China. Adherence to guideline-based secondary stroke prevention was defined as persistently receiving all of the five secondary prevention medications (antithrombotic, antidiabetic and antihypertensive agents, statin and anticoagulants) during hospitalization, at discharge, at 3, 6, and 12 months if eligible. The primary outcome was a new stroke at 12 months. @*Results@#Among 9,022 included patients (median age 63.0 years and 31.7% female), 3,146 (34.9%) were identified as adherence to guideline-based secondary prevention. Of all, 864 (9.6%) patients had recurrent stroke at 12 months, and the residual risk in patients with adherence to guidelinebased secondary prevention was 8.3%. Compared with those without adherence, patients with adherence to guideline-based secondary prevention had lower rate of recurrent stroke (hazard ratio, 0.85; 95% confidence interval, 0.74 to 0.99; P=0.04) at 12 months. Female, history of stroke, interleukin-6 ≥5.63 ng/L, and relevant intracranial artery stenosis were independent risk factors of the residual risk. @*Conclusions@#There was still a substantial residual risk of 12-month recurrent stroke even in patients with persistent adherence to guideline-based secondary stroke prevention. Future research should focus on efforts to reduce the residual risk.
ABSTRACT
Objective@#To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus(2019-nCoV) infection in children from six provinces (autonomous region) in northern China.@*Methods@#A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces(autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong.@*Results@#The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months -17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted > 3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 9%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate(19%,4/21), procalcitonin(4%,1/28), liver enzyme(22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred.@*Conclusions@#In this case series, 2019-nCoV infections in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis. After general treatment, the short-term prognosis is good.
ABSTRACT
Objective:To investigate the independent predictors for malignancy in colorectal laterally spreading tumors (LSTs) by therapeutic endoscopy.Methods:Data of consecutive patients with colorectal LSTs who underwent endoscopic treatment in Beijing Friendship Hospital between June 2013 and March 2019 were collected for retrospective analysis. Patients′ gender, age, body mass index, smoking history, and endoscopic and histological results were reviewed. Univariate analysis was used to identify the associated factors for malignancy of colorectal LSTs. Factors with statistical significance in univariate analysis were used in multivariate logistic regression to determine the independent predictors.Results:A total of 323 patients with 341 colorectal LSTs were involved in the study. The rate of malignancy was highest in non-granular pseudo depressed (NG-PD) subtype [85.48% (53/62)], followed by granular nodular mixed (G-NM) subtype [76.97% (117/152)]. Both of the above rates were significantly higher than that of granular homogenous (G-H) subtype [29.51% (18/61), P<0.001] and non-granular flat elevated (NG-FE) subtype [24.24% (16/66), P<0.001]. Univariate analysis showed that NG-PD subtype ( P<0.001, OR=18.40, 95% CI: 7.46-45.42), G-NM subtype ( P<0.001, OR=10.45, 95% CI: 5.30-20.58), rectosigmoid location ( P<0.001, OR=2.33, 95% CI: 1.47-3.69) and size ≥2 cm ( P<0.001, OR=2.60, 95% CI: 1.60-4.00) associated with malignancy for colorectal LSTs. In multivariate logistic regression, NG-PD subtype ( P<0.001, OR=17.51, 95% CI: 7.06-43.43), G-NM subtype ( P<0.001, OR=8.25, 95% CI: 4.07-16.73) and size ≥2 cm ( P=0.032, OR=1.80, 95% CI: 1.05-3.08) remained to be independent predictors. Conclusion:LSTs of NG-PD subtype, G-NM subtype or size ≥2 cm are high risk factors of malignancy, in which cases, en bloc resection is required.
ABSTRACT
Objective:To evaluate left lateral position I-scope tracheal intubation for optimizing anesthesia time during the patient′s general anesthesia before endoscopic submucosal dissection.Methods:A total of 150 patients with early upper gastrointestinal cancer were enrolled in the study for endoscopic submucosal dissection in Beijing Friendship Hospital, Capital Medical University from March to December 2018. Patients were randomly divided into three groups with 50 patients in each group. The SL group underwent I-scope tracheal intubation in the left lateral position, SS group underwent I-scope tracheal intubation in the supine position, and MS group underwent Macintosh laryngoscope tracheal intubation in the supine position. Preoperative non-essential anesthesia time (the time between successful intubation and operation), attempts for tracheal intubation and complications related to intubation were analyzed.Results:The preoperative non-essential anesthesia time was 8.55±2.16 min in SL group, 10.44±2.43 min in SS group, and 10.56±3.20 min in MS group, with significant difference among three groups ( F=9.08, P<0.001), and the time in SL group was shorter than that in SS group ( P<0.001) and MS group ( P<0.001). However, there was no statistical difference in non-essential anesthesia time between the SS group and MS group ( P=0.819). The success rate of first attempt intubation was 96.0% (48/50) in SL group, 90.0% (45/50) in SS group, and 92.0% (46/50) in MS group, with no significant differences among three groups ( χ2=2.601, P=0.627). The incidences of cough and expectoration, dry mouth and mucosal injury showed no statistical differences among three groups during transference to the ward after tracheal catheter removal (all P>0.05). The incidence of sore throat in MS group (38.0%, 19/50) was higher than that in SL group (18.0%, 9/50, P<0.05) and SS group (18.0%, 9/50, P<0.05), while the difference was not statistically significant between SL group and SS group ( P>0.05). Conclusion:I-scope tracheal intubation in the left lateral position may shorten the preoperative anesthesia time in patients undergoing general anesthesia for the operation in the left lateral position, and optimize overall anesthesia time.
ABSTRACT
Objective:To explore the value of ex- vivo porcine stomach model for endoscopic submucosal dissection (ESD) training for international trainees. Methods:Fifteen international students received ESD training and learning for twenty days. Firstly, students learned basic theory of ESD and completed a questionnaire. Then they were randomized to receive endoscopic training either on the vitro animal (group A) or on training experience (group B) of the clinical observation. At last, one case was assessed by an experienced endoscopist. The total and step-by-step operating time, complete resection, size of specimen and complications were recorded. All students completed the questionnaire once again. SPSS 20.0 was used for t test and chi-square test. Results:There was significant difference in total ESD operation time between group A and group B ( P<0.05). There were significant differences between the two groups on cutting time and dissection time, but there was no difference on marking time, injection time and operating speed. There was only one case of block resection and perforation in each group. For group A, their mastery and clinic confidence of ESD had been obviously increased after the animal training course. Compared with the operation before the training in group A, it was found that the total time and cutting time of the ESD after the training were also significantly improved. Conclusion:Theory combined with endoscopic training on vitro animal model can make the trainees familiar with the basic theory and master the operational skills, which is helpful and valuable for them to perform ESD in further clinic practice.
ABSTRACT
Huge improvement has been made in the diagnosis and treatment of endoscopic ultrasonography (EUS) and more doctors have begun to focus on this subject with the increased level of EUS. Beijing Friendship Hospital has built a comprehensive system for the teaching method and process which include basic information screening of trainee and standardized training of perceiving and operating ability. There were 3 grades training of computer simulation, animal simulation and operation on real patients. During the first month of training, trainees accepted training with computer simulator for at least 100 hours, and underwent animal simulator during the second month, then underwent EUS on the real patients under supervision of instructors during the third month. By doing this, residents can master the technique of treatment and diagnosis of EUS in a safer and better way.
ABSTRACT
Background@#and Purpose Previous studies suggested increased visit-to-visit variability of total cholesterol (TC) is associated with stroke. This study aimed to investigate the associations of various lipids measurements variability and the risk of stroke and stroke type (ischemic and hemorrhagic stroke). @*Methods@#Fifty-one thousand six hundred twenty participants in the Kailuan Study without history of myocardial infarction, stroke, and cancer who underwent three health examinations during 2006 to 2010 were followed for incident stroke. Variability in TC, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) measurements were measured using the coefficient of variation (CV), standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). @*Results@#During a median of 6.04 years of follow-up, 1,189 incident stroke (1,036 ischemic and 160 hemorrhagic stroke) occurred. In the multivariable-adjusted model, the hazard ratio (HR) comparing participants in the highest versus lowest quartile of CV of HDL-C were 1.21 (95% confidence interval [CI], 1.02 to 1.45; P for trend=0.013) for ischemic stroke. The highest quartile of CV of LDL-C was associated with 2.17-fold risk of hemorrhagic stroke (HR, 2.17; 95% CI, 1.25 to 3.75; P for trend=0.002) compared with the lowest quartile. We did not observe any significant association between TC and triglycerides variability with any of stroke. Consistent results were obtained when calculating variability index using SD, VIM, or ARV. @*Conclusions@#These findings suggest the high visit-to-visit HDL-C and LDL-C variability were associated with an increased incidence of ischemic and hemorrhagic stroke, respectively.
ABSTRACT
SOCS3, a feedback inhibitor of the JAK/STAT signal pathway, negatively regulates axonal regrowth and inflammation in the central nervous system (CNS). Here, we demonstrated a distinct role of SOCS3 in the injured spinal cord of the gecko following tail amputation. Severing the gecko spinal cord did not evoke an inflammatory cascade except for an injury-stimulated elevation of the granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFN-γ) cytokines. Simultaneously, the expression of SOCS3 was upregulated in microglia, and unexpectedly not in neurons. Enforced expression of SOCS3 was sufficient to suppress the GM-CSF/IFN-γ-driven inflammatory responses through its KIR domain by attenuating the activities of JAK1 and JAK2. SOCS3 was also linked to GM-CSF/IFN-γ-induced cross-tolerance. Transfection of adenovirus overexpressing SOCS3 in the injured cord resulted in a significant decrease of inflammatory cytokines. These results reveal a distinct role of SOCS3 in the regenerating spinal cord, and provide new hints for CNS repair in mammals.
ABSTRACT
Drug delivery systems (DDS) are defined as methods by which drugs are delivered to desired tissues, organs, cells and subcellular organs for drug release and absorption through a variety of drug carriers. Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility, drug aggregation, low bioavailability, poor biodistribution, lack of selectivity, or to reduce the side effects of therapeutic drugs. During 2015-2018, significant progress in the research on drug delivery systems has been achieved along with advances in related fields, such as pharmaceutical sciences, material sciences and biomedical sciences. This review provides a concise overview of current progress in this research area through its focus on the delivery strategies, construction techniques and specific examples. It is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.
ABSTRACT
Hyaluronic acid (HA) is a natural ligand of tumor-targeted drug delivery systems (DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors (HARE and LYVE-1) are also overexpressing in the reticuloendothelial system (RES). Therefore, polyethylene glycol (PEG) modification of HA-based DDS is necessary to reduce RES capture. Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement, significantly compromising the antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform (Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage. The and investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and nonspecific biodistribution.