OBJECTIVES: To develop an E-selectin-targeting nanomedicine delivery system that competitively inhibits E-selectin-neutrophil ligand binding to block neutrophil adhesion to vessels and suppress their recruitment to the lesion sites. METHODS: Doxorubicin hydrochloride (DOX)-loaded liposomes (IEL-Lip/DOX) conjugated with E-selectin-affinity peptide IELLQARC were developed using a post-insertion method. Two formulations [2-1P: Mol(PC): Mol(DPI)=100:1; 2-3P: 100:3] were prepared and their modification density and in vitro release characteristics were determined. Their targeting efficacy was assessed in a cell model of LPS-induced inflammation, a mouse model of acute lung injury (ALI), a rat femoral artery model of physical injury-induced inflammation, and a zebrafish model of local inflammation. RESULTS: The prepared IEL-Lip/DOX 2-1P and 2-3P had peptide modification densities of 4.76 and 7.57 pmoL/cm², respectively. Compared with unmodified liposomes, IEL-Lip/DOX exhibited significantly reduced 48-h cumulative release rates at pH 5.5. In the inflammation cell model, IEL-Lip/DOX showed increased uptake by activated inflammatory endothelial cells, and 2-1P exhibited a higher trans-endothelial ability. In ALI mice, the fluorescence intensity of IEL-Lip/Cy5.5 increased significantly in lung tissues by 53.71% [Z-(2-1P)] and 93.41% [Z-(2-3P)], and 2-1P had an increased distribution by 24.19% in the inflammatory lung tissue compared to normal mouse lung tissue. In rat femoral artery models, 2-1P had greater injured/normal vessel fluorescence intensity contrast. In the zebrafish models, both 2-1P and 2-3P showed increased aggregation at the site of inflammation. CONCLUSIONS This E-selectin-targeting nanomedicine delivery system efficiently targets activated inflammatory endothelial cells to increase drug concentration at the inflammatory site, which sheds light on new strategies for treating neutrophil-mediated inflammatory diseases and practicing the concept of "one drug for multiple diseases".
Animals ; Liposomes ; Rats ; Nanomedicine ; E-Selectin ; Drug Delivery Systems ; Inflammation/drug therapy* ; Mice ; Doxorubicin/analogs & derivatives* ; Zebrafish ; Acute Lung Injury/drug therapy*

Objective To explore the assisted reproductive strategy and influencing factors for patients undergoing frozen-thawed cycle blastocyst transfer after hysteroscopic adhesiolysis for intrauterine adhesions.Methods A total of 275 patients who underwent frozen-thawed cycle blastocyst transfer after hysteroscopic adhesiolysis for infertility reasons at the Reproductive Genetics Center of the First Affiliated Hospital of University of Science and Technology of China from January 2018 to December 2022 were included in the study.They were divided into a single blastocyst transfer group(n=182)and a double blastocyst transfer group(n=93).The clinical outcomes were analyzed and compared retrospectively between the group.Results The two groups showed no statis-tically significant differences in terms of age,day of endometrial thickness conversion,endometrial preparation method,clinical pregnancy rate,miscarriage rate,preterm birth rate,gestational week at delivery,and mode of delivery(P>0.05).The single blastocyst transfer group had significantly lower infertility duration(years)(2.43±1.64 vs.3.03±2.13,P<0.05),significantly lower AFS prognosis score(5.13±2.25 vs.5.72±2.19,P<0.05),and significantly lower multiple pregnancy rate(1.33%vs.28.57%,P<0.05),but significantly higher quality embryo rate(90.66%vs.46.24%,P<0.05),implantation rate(50.00%vs.34.41%,P<0.05),and live infant mass(g)(3236.84±565.35 vs.2976.44±692.79,P<0.05)compared to the double blastocyst transfer group.Binary logistic regression analysis showed that the number of high-quality embryos transferred and AFS score were independent influencing factors for clinical pregnancy(P<0.05).Conclusions The number of high-quality embryos transferred and the AFS score are independent influencing factors for clinical pregnancy in patients undergoing frozen-thawed cycle blastocyst transfer after hysteroscopic adhesiolysis for intrauterine adhesions.Single high-quality blastocyst transfer is a preferred treatment for patients after hysteroscopic adhesiolysis,and double blastocyst transfer is favor-able for patients with a poor prognosis to achieve better pregnancy outcomes.

ObjectiveTo evaluate the effect of standardized blood pressure measurement in consulting room （SBPM） model on blood pressure screening of non-hypertensive patients in community. MethodsFour communities were randomly selected from Fengxian District of Shanghai， and non-hypertensive patients in the communities were included for screening. Based on the communities， participants were further classified into the intervention group and control group. A one-year intervention study was conducted from January 1， 2021 to December 31， 2021. The intervention group received the intervention measures of standardized measurement， and the control group remained the routine measurement. The distribution of blood pressure values and last digit of the values between the intervention group and control group were tested using Chi-square test and normality test. Then changes in abnormal blood pressure rate before and after the intervention were determined by double difference method. Statistical analysis was performed using SPSS 20.0. ResultsA total of 15 368 participants were included in the intervention group， and 19 811 participants in the control group. After the intervention， range of the last digit of blood pressure values in the intervention group was 9.55%‒10.41%， of which that of systolic and diastolic blood pressure were equally distributed （P=0.932 and 0.871， respectively）. The range of the last digit in the control group was 1.31%‒42.58%， of which that of systolic and diastolic blood pressure showed unequal distribution （P<0.001）. Through one-year standardized measurement intervention， the abnormal rate of blood pressure in the intervention group was 26.29%， which was 7.61 times as high as that in the control group （OR=7.55， 95%CI： 6.75‒8.57， P<0.001）. ConclusionStandardized blood pressure measurement in consulting room is suitable for the screening of blood pressure measurement in community， which has higher data quality than that of routine measurement.

Background: The occurrence of gastrointestinal symptoms in cirrhotic patients with gastroesophageal varices (GOV) after endoscopic treatment is obvious, and the role of gastric myoelectrical activity (GMA) and autonomic nerve function imbalance in the development of gastrointestinal symptoms has not been clarified. Aims: To investigate the changes of GMA and autonomic nerve function in cirrhotic patients with GOV after endoscopic treatment. Methods: Twenty-five cirrhotic patients with GOV from May 2019 to October 2019 at the First Affiliated Hospital of Nanjing Medical University were enrolled, and 10 patients with gastric polyp were served as controls. Electrogastrogram (EGG) and heart rate variability (HRV) were detected before the operation, 1 day after the operation and 5 days after the operation in GOV group. For the gastric polyp group, EGG and HRV were detected before the operation and 1 day after the operation. Changes of GMA and autonomic nerve function were compared between the two groups. Results: No significant differences in GMA and autonomic nerve function were found between GOV group and gastric polyp group before and 1 day after the operation (P>0.05). LF, LF/HF were significantly increased 1 day after the operation in GOV group (P<0.05), while HF was significantly decreased (P<0.01), and the percentage of bradygastria was significantly increased (P<0.01). There were no significant differences in GMA and autonomic nerve function between pre-operation and 5 days after the operation in GOV group (P>0.05). There were no significant differences in GMA and autonomic nerve function 1 day after the operation compared with pre-operation in gastric polyp group (P>0.05). Compared with Child-Pugh A group, Child-Pugh B group had more obvious GMA abnormalities, and the difference was statistically significant (P<0.05). Conclusions: In cirrhotic patients with GOV, the percentage of bradygastria and the sympathetic activity increased, and the vagal activity decreased 1 day after the operation. These results suggest that GMA and autonomic nerve dysfunction may be related to the gastrointestinal symptoms after endoscopic treatment.

A method was developed for determination of 12 kinds of phosphate compounds in water and sediment by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) coupled with solid phase extraction (SPE) and ultrasonic extraction.The water samples were concentrated by HLB solid-phase extraction (SPE) column and eluted twice with ethyl acetate, ultrasonic solvent extraction for sediment samples and then repeated the operation of water samples after diluted with deionized water.The sample were separated on a ZORBAX Eclipse Plus C18 (150 mm × 2.1 mm, 3.5 μm) column by a gradient elution with 0.2% formic acid aqueous solution and methanol as the mobile phase.Ion mode analysis was monitored by high performance liquid chromatography mass spectrometer (MRM).The target compounds were quantified by external standard method.At the spiked levels (0.05, 0.1 and 0.5 μg/L), the average recoveries of 12 kinds of OPEs in water samples ranged from 66.4% to 115%, except for TMP (28.5%-47.8%) and TEHP (22.4%-73.8%).The relative standard deviation RSD (n=3) was 0.5%-9.09%, and the method quantification (MOQ) was 0.001-0.05 μg/L, However at the spiked levels of 5, 10 and 50 μg/kg, the average recoveries of 12 kinds of OPEs in sediment samples ranged from 65.4% to 120.0%, except for TMP (35.7%-44.9%) and TCEP (31.2%-48.9%).The relative standard deviation RSD (n=3) was 0.01%-9.54%, and the MOQ for sediment was 0.02-2.0 μg/kg dw.Based on the above methods, the detection and analysis of the targets in the water and sediments samples of Taihu Lake were carried out.The results showed that the concentrations of ΣOPEs were 0.1-1.7 μg/L and 8.1-420 μg/(kg dw), respectively.

Objective To systemic evaluate postoperative pulmonary function between segmentectomy and lobectomy in patients with early stage non-small cell lung cancer.Methods Computer searched was performed up to September 2016 at the Cochrane Library,PubMed,EMBASE,CBM,CNKI,VIP and Wanfang database,collected postoperative pulmonary function between segmentectomy and lobectomy in Patients with early stage Non-Small Cell Lung Cancer.Study selection,data collection and critical assessment of the included studies were performed according to the recommendations of the Cochrane Collaboration.Results Eight studies included 308 segmentectomy and 386 lobectomy were identified for inclusion.FVC％ (MD =9.91,95％ CI:3.53-16.30,P =0.002),postoperation / preoperation FVC％ (MD =6.74,95％ CI:5.52-7.79,P ＜0.05),FEV1％ (MD =13.25,95％ CI:10.25-16.26,P ＜ 0.05),postoperation / preoperation FEV1％ (MD =7.18,95 ％ CI:5.88-8.48,P ＜ 0.05) showed significant difference.Conclusion Pulmonary function index was superior to lobectomy after segmentectomy in patients with early stage lung cancer,and segmentectomy resection was more beneficial to preserve lung function.

Background Macular edema is one of the serious complications of central retinal vein occlusion (CRVO),and the present therapies are laser coagulation and intravitreal injection of anti-vascular endothelial growth factor(VEGF)drugs.Conbercept is humanized-monoclonal VEGF antibody and used for the treatment of retinal vascular diseases.However,fewer studies were focused on its application in macular edema secondary to CRVO.Objective The aim of this study was to compare the effectiveness and safety of conbercept with triamcinolone acetonide(TA)by intravitreal injections for macular edema secondary to CRVO. Methods A non-randomized controlled study was carried out under the approval of the informed consent of patients.Sixty eyes of 60 patients with macular edema secondary to CRVO were included in Weifang Yidu Central Hospital from March 2012 to August 2013.The eyes were divided into the conbercept group and TA group with 30 for each group.Conbercept and TA of 0.05 ml were intravitreally injected in different groups,and the best corrected visual acuity(BCVA),central macular thickness(CMT)measured by OCT,intraocular pressure(IOP)and relavant complications were examined before injection and 1 week,1 month,3 months and 6 months after injection.The treatment outcomes were compared intergrouply and along with time. Results The BCVA was evidently better in 1 week,1 month,3 months and 6 months after injection than that before injection both in conbercept group and TA group(all at P＜0.01),and the BCVA of TA group was better than that of conbercept group 1 week after injection(P＜0.05).The CMT values of Conbercept were(572.00± 100.01),(325.12±91.55),(280.00±92.37),(258.65 ±88.65),(300.00±87.64)μm,and those of TA group were(570.00± 102.21),(345.12±89.31),(290.00±80.27),(309.65 ±84.13)and(303.00±90.59)μm,and CMT value after injection was significantly lower in 1 week,1 month,3 months and 6 months after injection than that before injection both in the conbercept group and the TA group(all at P＜0.05),and CMT value was evidently reduced in the conbercept group compared with the TA group 3 months after injection(P＜0.05).The IOP was(15.20±3.52),(21.20±3.80),(26.40±4.00),(23.60±3.73)and(21.50±3.27)mmHg in the TA group before injection and 1 week,1 month,3 months and 6 months after injection,showing significnatly elavation after injection(all at P＜0.05),and the IOP at different time points was higher in the TA group than that in the conbercept group(all at P＜0.05).However,there was no considerable change of IOP before and after injection in conbercept group(all at P＜0.05). Conelutions Both conbercept and TA are effective for macular edema secondary to CRVO by intravtreal injection.Compared with TA,conbercept is much safer because of less risk of IOP rising after intravtreal injection.

Objective To investigate the effects of bone morphogenetic protein-7 ( BMP7 ) on insulin signaling transduction in C2C12 myotubes and HepG2 hepatocytes, and the underlying mechanisms were studied preliminarily.Methods The C2C12 myotubes and HepG2 cells were treated with BMP7 at different concentrations.The insulin signal transduction was analyzed by Western blot.Meanwhile, total RNA was extracted and quantitative PCR was employed for detecting the effects of BMP7 on gene expressions of effectors involved in insulin signal pathway.Furthermore, JNK signal pathway was also measured.Results The protein levels of p-IR, p-Akt and p-GSK3β, as well as glucose uptake, were significantly stimulated by insulin in the C2C12 myotubes and HepG2 cells.However, these stimulations induced by insulin were largely attenuated by BMP7.The mRNA levels of Akt1, Igf1r, Insr, and Irs1 were not altered by the treatment of BMP7.The JNK signal pathway was activated by a 5-min exposure of BMP7 in the HepG2 cells, and this activation was gradually reduced along with the treating time.Conclusion BMP7 attenuates the insulin signal transduction in the HepG2 cells and C2C12 myotubes, and this attenuation effect may be through JNK activation.

OBJECTIVETo describe clinical and genetic feature in a Chinese family with familial idiopathic basal ganglia calcification 3 (IBGC-3) caused by a novel mutation in the SLC20A2 gene.

METHODSClinical data was collected from a family with familial IBGC-3. All of the family members underwent cerebral CT. Potential mutation of the SLC20A2 gene were screened in the proband, 5 symptomatic patients, 5 asymptomatic family members, and 100 healthy Chinese controls. Exon 8 of the SLC20A2 gene was cloned into plasmid and sequenced.

RESULTSThere were 6 symptomatic patients (3 males and 3 females) in an autosomal dominant pedigree. The patients manifested as juvenile-onset paroxysmal kinesigenic dyskinesia, in addition to pyramidal signs in proband. 5 patients alive had calcification in bilateral basal ganglia and subcortical areas. One asymptomatic member also had calcification in the brain; and 2 cases of asymptomatic young members had bilateral globus pallidus calcification. A novel c.1086delC mutation in SLC20A2 gene has been identified in proband and 7 family members with intracranial calcification. The deletion mutation was not found in 2 family members without intracranial calcification and healthy controls members. There is no clear relationship between clinical symptoms and the severity of calcification in cerebral CT.

CONCLUSIONFamilial idiopathic basal ganglia calcification caused by the SLC20A2 gene mutation can manifest as juvenile onset paroxysmal kinesigenic dyskinesia. Further study should be done to validate the unrelated relationships between the severity of calcification in IBGC 3 cranial CT and clinical symptoms.

Adolescent ; Adult ; Basal Ganglia Diseases ; genetics ; Calcinosis ; genetics ; Child ; Female ; Humans ; Male ; Mutation ; Neurodegenerative Diseases ; genetics ; Sodium-Phosphate Cotransporter Proteins, Type III ; genetics ; Tomography, X-Ray Computed

Objective: To observe the effect of electroacupuncture (EA) on serum interleukin (IL)-6, IL-8 and IL-10 in rat models of cerebral ischemia-reperfusion, and to discover the mechanism of EA in preventing and treating cerebral ischemia.
Methods:Male Sprague Dawley (SD) rats were randomized into a sham-operation (SO) group, a model control (MC) group, and an EA group, which were sub-grouped into a 6-hour group and a 24-hour group. In the SO group, rats only received vessel separation with filament placed inside without any treatment. In the MC and EA groups, the focal cerebral ischemia-reperfusion model was induced by using modified Longa method with intraluminal filament. The MC group didn’t receive any treatment;the EA group received EA at Baihui (GV 20) and Dazhui (GV 14) with sparse-dense wave for 30 min. The levels of serum IL-6, IL-8 and IL-10 were detected by using Elisa test.
Results: Six hours after ischemia-reperfusion injury, the levels of serum IL-6, IL-8 and IL-10 in the MC group were significantly higher than those in the SO group (P<0.01, P<0.05, P<0.05);the level of serum IL-8 in the EA group was significantly lower than that in the MC group (P<0.05), while there were no significant differences in comparing IL-6 and IL-10 between the EA group and the MC group. Twenty-four hours after ischemia-reperfusion injury, the levels of serum IL-6 and IL-8 in the EA group were significantly lower than those in the MC group (both P<0.05), while there were no significant differences in comparing the level of IL-10 among the three groups.
Conclusion:Early intervention by EA can regulate the levels of serum IL-6 and IL-8 in cerebral ischemic injury.