Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

Objective:To investigate the feasibility and effectiveness of incision subcutaneous porous catheter combined with ropivacaine analgesia in enhanced recovery after laparoscopic gastrointestinal surgery.Methods:The clinical data of 140 patients underwent gastrointestinal surgery from August 2021 to April 2022 in Shanghai Fourth People′s Hospital, School of Medicine, Tongji University were retrospectively analyzed. Among them, 70 patients were given routine postoperative analgesia (control group), and 70 patients were given incision subcutaneous porous catheter combined with ropivacaine analgesia on the basis of routine postoperative analgesia (observation group). The visual analogue score (VAS) 4, 24, 32, 48, 56 and 72 h after operation was evaluated; and the complications of subcutaneous catheterization, incision infection, postoperative nausea vomiting, neurological symptoms, time to extubation, patient satisfaction degree, recovery time of intestinal function and hospital stay were recorded.Results:The VAS 4, 24, 32, 48, 56 and 72 h after operation in observation group was significantly lower than that in control group: 1.000 (- 0.250, 2.250) scores vs. 1.000 (- 1.000, 3.000) scores, 2.000 (1.000, 3.000) scores vs. 4.000 (2.000, 6.000) scores, 1.000 (0.000, 2.000) scores vs. 3.000 (1.000, 5.000) scores, 2.000 (1.000, 3.000) scores vs. 3.000 (1.750, 4.250) scores, (1.100 ± 0.934) scores vs. (2.085 ± 0.943) scores and (0.985 ± 0.842) scores vs. (1.814 ± 0.921) scores, and there was statistical difference ( P<0.05 or <0.01). The recovery time of intestinal function and hospital stay in observation group were significantly shorter than that that in control group: (1.743 ± 0.557) d vs. (2.200 ± 0.714) d and (8.043 ± 1.160) d vs. (8.757 ± 1.221) d, and there were statistical difference ( P<0.01); there were no statistical differences in the rate of incision infection, incidence of postoperative nausea vomiting, time to extubation and patient dissatisfaction rate between two groups ( P>0.05); there were no the complications of subcutaneous catheterization and neurological symptoms in two groups. Conclusions:The incision subcutaneous porous catheter combined with ropivacaine analgesia after laparoscopic gastrointestinal surgery is a safe, effective and feasible method. Multimodal analgesia under enhanced recovery after surgery can increase the postoperative recovery after gastrointestinal operations and shorten the postoperative hospital stay.

Objective:To explore the effect of online appointment system of standardized patients (SP) in cardiology practice teaching.Methods:The undergraduate students who entered the cardiology department of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine for clinical practice in 2018 and 2019 were selected as teaching objects, and they were divided into traditional teaching group ( n=30) and appointed SP teaching group ( n=30). After the teaching, SPSS 19.0 software was used for data analysis to compare the teaching effect of the two groups. Results:The scores of SP teaching group were higher than those of traditional teaching control group, with statistical significance ( P<0.05). Conclusion:Through constructing SP database and typical case database, online appointment system of SP for medical history inquiry and doctor-patient communication skills training can effectively solve the problems such as lack of clinical practice cases and doctor-patient contradiction, and greatly improve the teaching efficiency.

Aim To investigate the effect of Bigelovii A on HepG2 cell apoptosis and its possible mechanism. Methods MTT assay was used to determine the inhibitory effect of Bigelovii A on HepG2 cells. Flow cytometry was performed to detect apoptosis. Western blot was applied to detect the expression of proteins of STAT pathway. Results BA (20 μmol L

Objective:To explore the effect of online appointment system of standardized patient in cardiology practice teaching.Methods:The undergraduate students who entered the cardiology department for clinical practice in 2018 and 2019 were selected as teaching objects, and they were divided into traditional teaching group ( n=30) and appointed SP teaching group ( n=30). After the teaching, SPSS 19.0 software was used for data analysis to compare the teaching effect of the two groups. Results:The scores of SP teaching group were higher than those of traditional teaching control group, with statistical significance ( P<0.05). Conclusion:Through constructing standardized patient database and typical case database, online appointment system of standardized patient for medical history inquiry and doctor-patient communication skills training can effectively solve the problems such as lack of clinical practice cases and doctor-patient contradiction, and greatly improve the teaching efficiency.

Objective:To explore the application of optical coherence tomography (OCT) in the interventional diagnosis and treatment of intermediate coronary disease.Methods:Patients were enrolled during January 2017 to January 2019, in the Department of Cardiology, the Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine.The patient whose diagnosis was confirmed as intermediate coronary artery lesion by coronary angiography then underwent coronary OCT examination.The general information, disease history, drug use, biochemical indicators and OCT imaging indicators were collected.Results:(1)A total of 75 borderline lesions were detected in 69 patients with coronary heart disease, including 52 cases of left anterior descending artery (LAD) (75.4%), 4 cases of left circumflex artery (5.8%, 4/69), and 19 cases (27.5%, 19/69) of right coronary artery (RCA). (2) According to the analysis of the plaque characteristics of borderline lesions OCT, 7 cases were accompanied with thrombosis, 6 cases with plaque rupture, 25 cases with thin fiber cap lipid plaque, 49 cases with macrophages, 35 cases with microvascular, 35 cases with cholesterol crystallization, 3 cases with ulcer and 6 cases with intimal dissection.(3)The median of the minimum lumen area (MLA) determined by OCT was 2.9 mm 2.In the MLA<2.9 mm 2 group, C-reactive protein (CRP) ((2.92±2.44) mg/L vs.(1.98±1.30) mg/L, P=0.045), total cholesterol (TC) ((4.13±0.78) mmol/L vs.(3.74±0.75) mmol/L, P=0.041), low density lipoprotein cholesterol ((2.77±0.83) mmol/L vs.(2.22±0.78) mmol/L, P=0.007), small and dense LDL ((1.02±0.44) mmol/L vs.(0.80±0.34) mmol/L, P=0.024), lipoprotein a ((1.16±0.17) mg/L vs.(0.95±0.09) mg/L, P=0.042) were significantly higher than those in MLA≥2.9 mm 2 group.(4). According to the interventional strategy, patients were divided into two groups: percutaneous coronary intervention (PCI) group (N=16) and non-PCI group (N=59). The area stenosis (AS%) ((68.58±4.90)% vs.(63.10±7.09)%, P=0.001), diameter stenosis (DS%) ((65.65±6.91)% vs.(60.77±8.41)%, P=0.024), lipid plaque curvature ((245.3±41.0)° vs.(189.8±99.6)°, P=0.001), lipid plaque length ((19.11±6.40) mm vs.(14.72±9.30) mm, P=0.035) were deteriorated significantly in the PCI group than those in non-PCI group, the differences were all of them were statistically significant.(5)The incidence of 1-year major cardiovascular adverse events (MACE) was 6.25% in Oct guided PCI group and 5.08% in patients without PCI.There was no significant difference between the two groups ( P=0.317). Conclusion:According to the OCT assessment in the intermediate coronary lesions, it is found that the smaller the luminal area, the higher the serum LDL cholesterol level.More Interventional therapy were performed in the vulnerable plaques with large lipid cores.Decision-making for intermediate lesion was highly depended on the plaque tissue characteristics, rather than just MLA size.

Objective:To prepare a drug release system of drug-loaded cross-linked decellularized corneal stromal lenticules and evaluate its drug release characteristics in vitro. Methods:Lenticules were obtained during femtosecond laser-assisted small incision lenticule extraction (SMILE) surgery in Chongqing Aier Ophthalmology Hospital.Decellularized corneal stromal lenticules were prepared using high concentration sodium chloride (NaCl) combining nuclease.The decellularized corneal stromal lenticules were randomly divided into normal group, 0.5% levofloxacin group, 3% levofloxacin group and 5% levofloxacin group, with 4 lenticules in each group.The lenticules did not receive any treatment in the normal group, and drug-loading those were soaked in different doses of levofloxacin solution for three hours according to grouping.In the crosslinking test, 12 decellularized corneal stromal lenticules were randomly divided into non-crosslinking group, 0.01 mmol 1-(3-dimethylamino) propylimine (EDC) group, 0.05 mmol EDC group and 0.25 mmol EDC group.The lenticules for cross-linking were soaked in different contents of mixed solution of EDC with N-hydroxysuccinyl (NHS) for four hours respectively according to grouping, and then in 3% levofloxacin solution for three hours.Only 3% levofloxacin solution soaking was carried in the non-crosslinking group.High performance liquid chromatography (HPLC) was employed to detect the drug release concentration of the lenticules, and spectral scanning method was performed to measure light transittance of the lenticules.The surface ultrastructure of the decellularized lenticules among different cross-linking groups was examined and compared with scanning electron microscope.The use of the human corneal lenticules was approved by an Ethics Committee of Chongqing Aier Ophthalmology Hospital (No.2019012). Written informed consent was obtained from each patient before surgery.Results:The release concentrations of decellularized corneal stroma lenticules were significantly different at 1 day, 7, 14, and 21 days among 0.5%, 3%, and 5% levofloxacin group ( P<0.05) or also among the 0.01 mmol EDC, 0.05 mmol EDC, and 0.25 mmol EDC cross-linked groups ( P<0.01). The drug release concentrations in 0.05 mmol EDC group were the highest at various time points, and the release time of the three cross-linked groups lasted until 21 days after release concentrations of decellularized corneal stroma lenticules.The drug release concentrations in cross-linked groups and non-crosslinking group were gradually declined with the prolong of drug-loading time, showing a significant difference at different time points ( P<0.05). The transmittance of the lenticules was (88.68±1.19)% and (91.55±1.16)% in the non-crosslinking group and normal group, respectively, with no significant difference ( P>0.05). The average transmittance of the lenticules was significantly reduced in the drug-loaded groups compared with the normal group ( P<0.05). The smaller collagen fiber voids and closely arranged collagen fibers were displayed in the cross-linking groups under the scanning electron microscope with the best effect in the 0.25 mmol EDC group. Conclusions:EDC/NHS cross-linking can improve the drug-loading effect of decellularized corneal stromal lenticules probably by lessening collagen fiber voids.The drug-loaded cross-linked decellularized corneal stromal lenticules have a good drug release effect in vitro.

OBJECTIVETo analyze a fetus with abnormal cardiac ultrasound by using various techniques and explore its genotype-phenotype correlation.

METHODSLymphocytes derived from umbilical cord blood sample were subjected to G-banding analysis. Short tandem repeats quantitative fluorescence PCR (STR-QF-PCR) was used for analysis of fetal DNA as an auxiliary test. Low-coverage whole genome sequencing (WGS) was used to detect chromosomal deletion/duplication which exceeded 100 kb in size.

RESULTSThe karyotype of the fetus was 47,XN,+mar. As detected by STR-QF-PCR, the copy number of GATA178F11 locus on chromosome 18 was 4, and the duplicated fragment was derived from the mother. WGS suggested that the fetus to be 46,XN,dup(18p11.21p11.32).seq [GRCh37/hg19](10 001-15 378 887)× 4, with the duplicated fragment spanning approximately 15.38 Mb.

CONCLUSIONThe cardiac malformation of the fetus may be attributed to the partial duplication of chromosome 18p. Combined cytogenetic and molecular methods can facilitate prenatal detection of genetic abnormalities.

Objective:To study relationship among serum homocysteine (Hcy) level ,paraoxonase 1 (PON1) activity and carotid atherosclerosis .Methods:A total of 179 residents from a community of Shanghai ,who participated in cardiovascular risk factor screening from 2012 to 2014 ,were selected .They received carotid ultrasonic examination and measurements of serum Hcy ,PON1 and other biomarkers .According to serum Hcy level ,subjects were divided into elevated Hcy group (n=85) and normal Hcy group (n=94) .Results:Spearman correlation analysis indicated that serum Hcy level was significant inversely correlated with PON1 activity (r= -0.738 ,P=0.001) .Compared with normal Hcy group ,there were signifi‐cant rise in age [(60.66 ± 7.18) years vs .(64.57 ± 7.29) years] ,male proportion (27.66% vs .63.53% ) ,serum creati‐nine [(69.62 ± 12.76)μmol/L vs .(88.47 ± 20.86)μmol/L] ,uric acid [(267.85 ± 63.02)μmol/L vs .(307.51 ± 76.07)μmol/L] ,triglyceride [(1.33 ± 0.79) mmol/L vs .(1.76 ± 1.70) mmol/L]and systolic blood pressure [(134.93 ± 15.82) mmHg vs .(142.72 ± 17.86) mmHg] ,and significant reductions in levels of high density lipoprotein cholesterol [HDL‐C , (1.17 ± 0.26) mmol/L vs .(1.06 ± 0.27) mmol/L]and PON1 [(288.58 ± 73.80) kU/L vs .(187.81 ± 16.31) kU/L]in el‐evated Hcy group , P<0. 05 or <0. 01. Incidence rate of carotid atherosclerosis in elevated Hcy group was significantly higher than that of normal Hcy group (64. 7% vs .44. 7% ) , P=0. 001 .Multi‐variate gradual Logistic regression analysis indicated that serum creatinine and Hcy levels were independent risk factors for serum PON 1 activity(OR=1.055 ,1.139 , P<0.01 ,<0.05);Hcy isn′t an independent risk factor (OR=1.020 ,P=0.497) for carotid atherosclerosis .Conclusion:Serum Hcy level is significant inversely correlated with serum PON 1 activity ,and both of them are related to occurrence of carotid atherosclerosis .

Objective To establish a simple, efficient and low-cost method for the detection of Salmonella typhimurium carrying SSeC gene. Methods In this study, a nano-biosensor ( FAM-P/GO) was successfully established based on the noncovalent assembly of carboxy-fluorescein ( FAM)-labeled probe and graphene oxide ( GO) . The target gene at different concentrations and SSeC gene-harbored bacterium sam-ples were detected by the FAM-P/GO nano-biosensor to evaluate its sensitivity. The specificity of the estab-lished nano-biosensor was evaluated by using DNAs with mismatched base pairs and single-stranded DNAs ( ssDNAs) extracted from various species. Results The established strategy for SSeC gene detection showed a good linear range of 0. 05-1. 0 μmol/L (R2=0. 992 1) with a lower limit of 0. 05 μmol/L. Moreover, the lower detection limit for target bacterium samples was 103 CFU/ml and the fluorescence intensity increased linearly with the concentration from 103 CFU/ml to 108 CFU/ml. The signal-to-noise ( S/N) of the experi-mental group was much greater than that of the control group, which indicated that the establish method was highly specific. Conclusion The FAM-P/GO nano-biosensor was successfully established in this study, which provided a new and possible way for the rapid detection of Salmonella typhimurium harboring SSeC gene.