1.Nose-to-brain delivery of targeted lipid nanoparticles as two-pronged β-amyloid nanoscavenger for Alzheimer's disease therapy.
Yanyan XU ; Xiangtong YE ; Yanfeng DU ; Wenqin YANG ; Fan TONG ; Wei LI ; Qianqian HUANG ; Yongke CHEN ; Hanmei LI ; Huile GAO ; Weiwei ZHANG
Acta Pharmaceutica Sinica B 2025;15(6):2884-2899
Alzheimer's disease (AD), characterized by β-amyloid (Aβ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α-mangostin (α-M) and β-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α-M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting Aβ production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α-M reversed Aβ-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of Aβ, while siB effectively suppressed BACE1 expression, abrogating Aβ synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial Aβ plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.
2.Correlation analysis of preoperative red blood cell distribution width and prognosis of patients undergoing TACE for hepatocellular carcinoma
Tingsong YING ; Zhixiang FAN ; Hao XU ; Wang LIU ; Rujian WANG ; Qingqiao ZHANG ; Ning WEI ; Yanfeng CUI ; Hongtao LIU
Chinese Journal of Hepatobiliary Surgery 2024;30(3):166-170
Objective:To evaluate the relationship between red blood cell distribution width (RDW) and prognosis of patients with hepatocellular carcinoma (HCC) andergoing transcatheter arterial chemoembolization (TACE).Methods:Clinical data of 212 patients with HCC andergoing TACE for the first time in Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University from January 2011 to May 2018 were retrospectively analyzed, including 184 males and 28 females, aged (56.8±11.2) years. Follow-up for survival. X-tile software was used to determine 13.1% as the optimal threshold for preoperative RDW prediction of prognosis, and enrolled patients were divided into a low level group (RDW<13.1%, n=70) and a high level group (RDW≥13.1%, n=142). Aspartate aminotransferase, total bilirubin, albumin, hemoglobin and lipoprotein a, Barcelona clinical liver cancer (BCLC) stage and other indexes were compared between the two groups. Survival analysis was performed by Kaplan-Meier method, survival rate was compared by log-rank test, and the effect of RDW on prognosis was analyzed by Cox regression. Results:The 1-year, 2-year and 3-year cumulative survival rates in RDW high level group were 34.5%, 14.1% and 6.3%, respectively, while those in RDW low level group were 64.3%, 38.6% and 21.4%, respectively, with significant difference ( χ2=23.09, P<0.001). Compared with the low level group, the levels of aspartate aminotransferase and total bilirubin were higher, the levels of albumin, hemoglobin and lipoprotein a were lower, the proportion of portal vein cancer thrombin was higher, and the stage of BCLC was later, with statistical significance (all P<0.05). Cox regression analysis showed that HCC patients with RDW≥13.1%( HR=1.732, 95% CI: 1.223-2.452, P=0.002) had poor survival prognosis after TACE. Conclusion:Preoperative RDW≥13.1% is an independent risk factor for survival after TACE in patients with HCC. RDW has potential predictive value for prognosis of patients with HCC.
3.Clinical efficacy of mandibular angle osteotomy by three-point wiring localization on improvement of facial contour
Yanfeng ZHAO ; Jing ZHANG ; Qiaoli FAN
Chinese Journal of Medical Aesthetics and Cosmetology 2024;30(3):231-233
Objective:To investigate the clinical application of three-point wiring localization in mandibular angle osteotomy.Methods:A total of 180 patients with mandibular angle long curve osteotomy were selected in Sichuan Friendship Hospital from July 2021 to April 2022, aged 19-45 (mean age 26.0±10.0) years, including 30 males and 150 females. Preoperative bilateral mandible was symmetry as CT showed, and all of them undergo operation of mandibular angle long curve osteotomy by using three-point wiring localization method under tracheal intubation general anesthesia.Results:Bilateral osteotomy bone of mandibular angle was basically symmetrical in all patients, the arc of osteotomy was good, and there were no obvious complications after surgery. The postoperative follow-up was 3-12 months, and all cases had good postoperative face contour and bilateral symmetry.Conclusions:Using three-point wiring localization method at operation of long curve mandibular angle osteotomy can ensure bilateral symmetry, accuracy and safety of the osteotomy.
4.Application progress of speckle tracking imaging in the diagnosis and evaluation of congenital heart disease
Bo YU ; Kun SHI ; Xiaoyan WANG ; Lingxia FAN ; Yanfeng YANG
Chinese Pediatric Emergency Medicine 2024;31(10):788-792
The early diagnosis of congenital heart disease is very important. Ultrasound is widely used in the early diagnosis and evaluation of congenital heart disease because of its advantages of non-radiation, non-invasive property and portability.Speckle tracking imaging has the advantages of being free from angle, efficient and accurate, which makes up for some shortcomings of traditional echocardiography. It greatly improves the diagnosis accuracy of fetal congenital heart disease, especially congenital heart disease with outflow tract obstruction.Myocardial strain index and left ventricular torsion can more accurately evaluate myocardial function,help to judge prognosis, choose the time of operation and assist perioperative management. Blood speck tracking helps identify different blood flow patterns and may become an important diagnostic tool for the diagnosis and treatment of congenital heart disease.
5.Relationship between heart rate variability, deceleration capacity and cardiovascular metabolic diseases in children and adolescents with normal weight obesity
Bo YU ; Kun SHI ; Xiaojuan ZHOU ; Xiaoyan WANG ; Lingxia FAN ; Feifei SI ; Yanfeng YANG
Chinese Journal of Applied Clinical Pediatrics 2024;39(6):450-454
Objective:To investigate the relationship between heart rate variability(HRV), deceleration capacity(DC) and cardiovascular metabolic disease(CMD) in children and adolescents with normal weight obesity(NWO).Methods:A total of 200 children and adolescents aged 6-17 who underwent normal physical examination in Chengdu Women′s and Children′s Central Hospital from December 2022 to June 2023 were included in this retrospective case-control study.They were divided into the NWO group, normal weight lean(NWL) group, and overweight-obesity(OW-OB) group according to their body mass index(BMI) and body fat percentage(BF%).Fifty children were enrolled into the NWO group; fifty-one children were enrolled into the NWL group; and 99 children were enrolled into the OW-OB group.All the subjects received 24-hour heart monitoring, and their HRV indexes, such as the standard deviation of N-N interval in normal sinus(SDNN), the standard deviation of the mean value N-N intervals every 5-minute(SDANN), the mean of the standard deviations of all N-N intervals for each 5-minute segment of 24 hours(SDNNindex), the root mean square of successive N-N interval difference(rMSSD), the proportion of N-N 50(the successive N-N interval differences>50 ms) in the total number of N-N intervals(pNN50), and DC were automatically calculated.Blood pressure, fasting blood glucose and blood lipids were measured, and the cardiometabolic risk score(CRS) was obtained through the accumulation of relevant factors.The general data, SDNN, SDANN, SDNNindex, rMSSD, pNN50, DC and CRS of the three groups were compared by variance analysis.Spearman correlation and multivariate Logistic regression were used to analyze the risk factors affecting CRS.Results:There was no significant difference in age, gender and other general information among the three groups(all P>0.05).SDNN in the NWO, NWL, and OW-OB groups were(120.88±16.36) ms, (129.07±16.36) ms, and(109.29±16.38) ms, respectively( F=26.231, P<0.001); SDANN were(64.44±11.61) ms, (66.25±8.34) ms, and(61.70±6.85) ms, respectively( F=5.048, P=0.007); rMSSD were(27.02±3.87) ms, (27.51±5.92) ms, and(25.12±6.78) ms, respectively( F=3.328, P=0.038); pNN50 were(12.62±4.04)%, (13.39±2.26)%, and(11.22±2.93)%, respectively( F=9.099, P<0.001); DC were(4.83±0.20) ms, (4.94±0.33) ms, and(4.63±0.28) ms, respectively( F=23.496, P<0.001)and CRS was 0.94±0.87, 0.69±0.19 and 1.57±1.07, respectively( P<0.01).The differences between the three groups were statistically significant.Spearman correlation analysis showed that BMI( r=0.211, P=0.003) and BF%( r=0.558, P<0.001) were significantly positively correlated with CRS, while SDNN( r=-0.258, P<0.001) and DC( r=-0.499, P<0.001) were significantly negatively correlated with CRS.Multivariate Logistic regression analysis showed that BF%(95% CI: 0.098-0.265, P<0.001) and DC(95% CI: -3.962--1.391, P<0.001) were independent risk factors for predicting CMD. Conclusions:Increased BF% and decreased DC are independent risk factors for CMD.Analysis of body composition and HRV in children and adolescents can help to identify potentially high-risk groups more accurately, intervene early, and reduce the risk of CMD.
6.Facial contouring surgery combined with the clinical application of minimally invasive tunnel separation and lifting technique
Yanfeng ZHAO ; Jing ZHANG ; Qiaoli FAN
Chinese Journal of Medical Aesthetics and Cosmetology 2023;29(1):23-25
Objective:To explore a simple and effective clinical method for improving facial sagging while performing maxillofacial contouring surgery.Methods:From October 2020 to October 2021, 50 patients with mandibular angle and malar surgery in the Plastic Surgery Department of Sichuan Friendship Hospital were selected, aged 30-43 years, with the average age of 37 years, including 44 females and 6 males. Maxillofacial contouring surgery was performed under transnasal intubation general anesthesia, the interorgual jaw groove incision was performed with a swing saw for bilateral long arc osteotomy, and the maxillary gingival groove incision and sideburn skin incision were performed for zygomatic osteotomy reduction and zygomatic arch incision. A small incision about 3 mm long was taken 1 cm from the edge of the temporal hair; a special conical cannula stripper was used to perform subcutaneous tunnel peeling to the zygomatic fat pad and masseter muscle ligament, anterior appendage ligament, then a two-way barb line was placed through the casing to lift vertically upwards, pierce above the posterior papillae of the ear, and the excess thread was cut off.Results:Following-up for 3-12 months, all recipients recovered well after surgery, the skin of the middle and lower parts of the postoperative body was lifted to varying degrees, the cheek fat pad was lifted, the jaw contour line was clearer, and the nasolabial fold was significantly improved as compared with that before the operation.Conclusions:At the same time as facial contouring surgery, the use of minimally invasive tunnel separation and lifting technique can effectively improve the skin sagging in the middle and lower parts, and it is simple and effective, and the clinical application effect is good.
7.Clinical study of Z-shaped titanium plate internal fixation technology in reduction malarplasty
Yanfeng ZHAO ; Jing ZHANG ; Qiaoli FAN
Chinese Journal of Plastic Surgery 2023;39(9):996-1002
Objective:To investigate the application of internal fixation technique using Z-shaped titanium plate during operation of reduction malarplasty.Methods:A retrospective analysis was performed for the clinical data of patients who underwent reduction malarplasty in Sichuan Friendship Hospital from June 2021 to March 2022. The intraoral maxillary vestibular groove mucosal incision and a small incision at the sideburns were used, and according to the height of the zygomatic body to be lowered before surgery, the zygomatic body was inverted F-shaped osteotomy, so that the zygomatic complex anterior was completely loosened. Zygomatic arch anterior to the temporomandibular joint was osteotomy using reciprocating saws and then push inward. The 3-hole titanium plate was bent into a Z-shape, the length of the middle arm of the Z-shaped titanium plate was the distance that the zygomatic arch needs to push inward, for the asymmetry of the zygomatic arch width on both sides, the length of the middle arm of the Z-shaped titanium plate on both sides can be adjusted and fixed with 2 titanium nails. Adjust the anterior zygomatic body so that the osteotomy line was well aligned and fixed with an L-shaped titanium plate. Selected 20 cases with complete three-dimensional(3D) CT data before and 3 months after surgery by random number table, and measured the vertical distance from the outermost point of the zygomatic arch to the median line based on the 3D CT head up position, and the surgical effect was evaluated. SPSS 25.0 software was used to statistically analyze the data, and the quantitative data conforming to the normal distribution were represented by Mean±SD, and the vertical distance from the outermost point of the zygomatic arch to the median line was compared by paired-sample t-test, P<0.05 indicates that the difference is statistically significant. Results:A total of 78 zygomatic plastic surgery patients were enrolled, including 18 males and 60 females, aged 19-37 years old, with an average age of 26 years. All patients’ incision had no complications after surgery, followed up for 3-12 months, the width of the zygomatic arch on both sides was significantly reduced, CT showed that the unilateral zygomatic arch was reduced by 3-8 mm, the transition between the zygomatic and temporal regions was smooth, and the zygomatic arch width on both sides was symmetrical. The difference of the vertical distance from the outermost point of the zygomatic arch to the median line was statistically significant between preoperative and postoperative, on the left side of the patient [(66.5±5.2) mm vs. (61.9±3.2) mm] and [(67.4±4.7) mm vs. (62.1±2.7) mm] ( P<0.05) for the right side. There was no significant difference between the left and right sides after surgery ( P>0.05). Conclusion:The Z-shaped titanium plate internal fixation technique can better control the zygomatic arch internal push distance in reduction malarplasty, and a symmetrical and gentle facial morphology can be obtained after surgery.
8.Clinical study of Z-shaped titanium plate internal fixation technology in reduction malarplasty
Yanfeng ZHAO ; Jing ZHANG ; Qiaoli FAN
Chinese Journal of Plastic Surgery 2023;39(9):996-1002
Objective:To investigate the application of internal fixation technique using Z-shaped titanium plate during operation of reduction malarplasty.Methods:A retrospective analysis was performed for the clinical data of patients who underwent reduction malarplasty in Sichuan Friendship Hospital from June 2021 to March 2022. The intraoral maxillary vestibular groove mucosal incision and a small incision at the sideburns were used, and according to the height of the zygomatic body to be lowered before surgery, the zygomatic body was inverted F-shaped osteotomy, so that the zygomatic complex anterior was completely loosened. Zygomatic arch anterior to the temporomandibular joint was osteotomy using reciprocating saws and then push inward. The 3-hole titanium plate was bent into a Z-shape, the length of the middle arm of the Z-shaped titanium plate was the distance that the zygomatic arch needs to push inward, for the asymmetry of the zygomatic arch width on both sides, the length of the middle arm of the Z-shaped titanium plate on both sides can be adjusted and fixed with 2 titanium nails. Adjust the anterior zygomatic body so that the osteotomy line was well aligned and fixed with an L-shaped titanium plate. Selected 20 cases with complete three-dimensional(3D) CT data before and 3 months after surgery by random number table, and measured the vertical distance from the outermost point of the zygomatic arch to the median line based on the 3D CT head up position, and the surgical effect was evaluated. SPSS 25.0 software was used to statistically analyze the data, and the quantitative data conforming to the normal distribution were represented by Mean±SD, and the vertical distance from the outermost point of the zygomatic arch to the median line was compared by paired-sample t-test, P<0.05 indicates that the difference is statistically significant. Results:A total of 78 zygomatic plastic surgery patients were enrolled, including 18 males and 60 females, aged 19-37 years old, with an average age of 26 years. All patients’ incision had no complications after surgery, followed up for 3-12 months, the width of the zygomatic arch on both sides was significantly reduced, CT showed that the unilateral zygomatic arch was reduced by 3-8 mm, the transition between the zygomatic and temporal regions was smooth, and the zygomatic arch width on both sides was symmetrical. The difference of the vertical distance from the outermost point of the zygomatic arch to the median line was statistically significant between preoperative and postoperative, on the left side of the patient [(66.5±5.2) mm vs. (61.9±3.2) mm] and [(67.4±4.7) mm vs. (62.1±2.7) mm] ( P<0.05) for the right side. There was no significant difference between the left and right sides after surgery ( P>0.05). Conclusion:The Z-shaped titanium plate internal fixation technique can better control the zygomatic arch internal push distance in reduction malarplasty, and a symmetrical and gentle facial morphology can be obtained after surgery.
9.Influence of Tuina plus oxiracetam on serum inflammatory factors and oxidative stress in mild vascular dementia patients
Nan GU ; Yuexian FAN ; Ling ZHOU ; Yan ZHANG ; Weijie BAI ; Yanfeng LI ; Liyun YANG ; Jinlong LI ; Jue HONG
Journal of Acupuncture and Tuina Science 2022;20(4):273-280
Objective: To observe the clinical efficacy of Tuina (Chinese therapeutic massage) plus oxiracetam in treating mild vascular dementia (VD) and seek its underlying mechanism. Methods: Ninety-six patients with mild VD were randomized into an observation group and a control group, with 47 cases in the observation group and 49 cases in the control group. The control group received oral oxiracetam capsules for treatment, and the observation group was given additional Tuina treatment. Before and after treatment, the mini-mental state examination (MMSE) was adopted to assess the patient's cognitive function; the activities of daily living (ADL) scale was used to evaluate their ability to conduct daily activities; changes in the serum inflammatory factors and oxidative stress indicators were also detected. Results: After treatment, the serum content of malondialdehyde (MDA) decreased in both groups (P<0.05) and was lower in the observation group than in the control group (P<0.05); the serum contents of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) increased in both groups (P<0.05) and were higher in the observation group than in the control group (P<0.05); the serum contents of interleukin (IL)-1, tumor necrosis factor (TNF)-α, IL-6, and IL-8 declined in both groups (P<0.05) and were lower in the observation group than in the control group (P<0.05). After the intervention, the levels of systolic velocity (Vs) and mean velocity (Vm) of the middle cerebral artery elevated, and the pulsatility index (PI) dropped in patients in the two groups, showing significant intra-group differences (P<0.05); the levels of Vs and Vm in the observation group were higher than those in the control group, and the PI was lower in the observation group than in the control group, showing significant between-group differences (P<0.05). The MMSE and ADL scores increased in both groups after the intervention (P<0.05) and were higher in the observation group than in the control group (P<0.05). Conclusion: In the treatment of mild VD, Tuina plus oxiracetam can improve the cerebral blood supply, ADL, and cognitive function; the mechanism may be associated with the reduction of oxidative stress damages and inflammatory reactions.
10.Transcatheter closure of atrial septal defect with deficient rim in children
Lingxia FAN ; Kun SHI ; Yonghong GUO ; Yanfeng YANG ; Xianmin WANG
Chinese Journal of Applied Clinical Pediatrics 2021;36(9):678-681
Objective:To evaluate the feasibility of transcatheter atrial septal defect(ASD) closure with deficient rim.Methods:From January 2017 to November 2019, patients at the Department of Pediatric Cardiology, Chengdu Women′s and Children′s Central Hospital were diagnosed as the secondary ASD and divided into 2 groups based on whether it has deficient rim[the deficient rim group (experimental group) and non deficient rims group (control group)]. The complications should be followed for 1-2 years.Results:A total of 66 patients, including 17 males (25.8%) and 49 females (74.2%), had the median age of 4 years and 2 months (2 years and 1 month-16 years), and the median body mass was 15.0 kg, ranging from 9.0 kg to 60.0 kg, with 23 cases (34.8%) in the experimental group and 43 cases (65.1%) in the control group.There were no statistically significant differences in gender, age, body weight, size of ASD, fluoroscopic dose, electrocardiogram, and pulmonary artery pressure between the two groups (all P>0.05). The immediate success rate was 95.4%(63/66 cases). There were no statistically significant differences between the surgical success rate [91.3%(21/23 cases) vs.97.6%(42/43 cases)] and the incidence of residual shunt [30.4%(7/23 cases) vs.16.2%(7/43 cases)](all P>0.05). And there were no statistically significant differences of the incidence of residual shunt between groups at each follow-up point ( P>0.05). No arrhythmia occurred in the experimental group during follow-up, and 1 case of atrioventricular block in the control group persisted until the time of publication.A total of 4 cases of frequent atrial premature beats or non-paroxysmal atrial tachycardia returned to normal at the follow-up node 6 months after intervention. Conclusions:Under the selection of appropriate cases and skilled catheter technology, the transcatheter treatment of ASD in children with deficient rims is feasible.

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