Aim To explore the effect of Pueraria Lobata Flowers Extract(PFE)on lipid accumulation in mac-rophage-derived foam cells.Methods The concentration of PFE in THP-1-derived foam cells was screened by MTT,intracellular lipid accumulation was detected by oil red O staining and cholesterol detection kit,intracellular cholesterol ef-flux levels were detected by cholesterol efflux assay kit,RT-qPCR and Western blot were used to analyze mRNA and pro-tein expression.Results PFE significantly reduced lipid accumulation in THP-1-derived foam cells.PFE did not affect the mRNA expression of CD36,scavenger receptor-A Ⅰ(SR-A Ⅰ),sterol regulatory element-binding protein 2(SREBP2),3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR),but it could upregulate the mRNA and protein expres-sion levels of ATP-binding cassette transporter A1(ABCA1)(P＜0.05),and promote the intracellular cholesterol efflux of macrophage-derived foam cells(P＜0.01).PFE could activate the activity of peroxisome proliferator-activated receptor y(PPARγ)(P＜0.01)and upregulate the mRNA and protein expression levels of PPARγ(P＜0.05).Compared with the PFE control group,the expression of PPARγ and ABCA1 proteins decreased and cholesterol efflux decreased after GW9662 treatment(all P＜0.01).Conclusion PFE could significantly prevent the lipid accumulation in THP-1-derived foam cells and inhibit the formation of foam cells by upregulating ABCA1 expression and cholesterol efflux mediated by PPARγ.

Objective:To evaluate the effect of hyperthermia on radiation pneumonitis (RP) in elderly patients with esophageal cancer undergoing intensity-modulated radiotherapy (IMRT).Methods:Clinical data of 177 elderly esophageal cancer patients (aged ≥60 years) receiving IMRT in the First Affiliated Hospital of Soochow University and Yixing Cancer Hospital from August 1, 2017 to February 6, 2023 were retrospectively analyzed. Patients were divided into the hyperthermia and non-hyperthermia groups based on whether they received hyperthermia treatment. Patients in two groups received IMRT with 6 MV X-rays. Patients in the hyperthermia group underwent high-frequency hyperthermia within 1 h before radiation using the external thermotherapy device HG-2000Ⅲ (heating temperature: 41-43 ℃ for 40 min, twice a week). After adjusting for confounding factors between two groups using propensity score matching (PSM), the short-term effective rates between two groups were compared using Chi-square test. Univariate analysis and logistic multivariate analysis were employed to compare the incidence of RP between two groups. Results:After applying PSM, 42 pairs were successfully matched, and the baseline data and radiotherapy parameters showed no statistically significant differences between two groups (all P>0.05). The objective response rate (ORR) in the hyperthermia group was significantly higher than that in the non-hyperthermia group (83.3% vs. 64.3%, P=0.047). Univariate analysis revealed that the incidence of RP and symptomatic RP (≥ grade 2) in the hyperthermia group was significantly lower than that in the non-hyperthermia group (61.9% vs. 85.7%, P=0.013; 21.4% vs. 47.6%, P=0.012). Logistic multivariate analysis indicated that hyperthermia was an independent protective factor for symptomatic RP ( P=0.011). Conclusions:The incidence and severity of RP in elderly esophageal cancer patients receiving IMRT can be reduced by hyperthermia. Hyperthermia, as a clinically beneficial green treatment, improves efficacy and reduces toxicity for patients with esophageal cancer.

Objective:To construct an artificial intelligence-assisted diagnosis system to recognize the characteristics of Helicobacter pylori ( HP) infection under endoscopy, and evaluate its performance in real clinical cases. Methods:A total of 1 033 cases who underwent 13C-urea breath test and gastroscopy in the Digestive Endoscopy Center of Renmin Hospital of Wuhan University from January 2020 to March 2021 were collected retrospectively. Patients with positive results of 13C-urea breath test (which were defined as HP infertion) were assigned to the case group ( n=485), and those with negative results to the control group ( n=548). Gastroscopic images of various mucosal features indicating HP positive and negative, as well as the gastroscopic images of HP positive and negative cases were randomly assigned to the training set, validation set and test set with at 8∶1∶1. An artificial intelligence-assisted diagnosis system for identifying HP infection was developed based on convolutional neural network (CNN) and long short-term memory network (LSTM). In the system, CNN can identify and extract mucosal features of endoscopic images of each patient, generate feature vectors, and then LSTM receives feature vectors to comprehensively judge HP infection status. The diagnostic performance of the system was evaluated by sensitivity, specificity, accuracy and area under receiver operating characteristic curve (AUC). Results:The diagnostic accuracy of this system for nodularity, atrophy, intestinal metaplasia, xanthoma, diffuse redness + spotty redness, mucosal swelling + enlarged fold + sticky mucus and HP negative features was 87.5% (14/16), 74.1% (83/112), 90.0% (45/50), 88.0% (22/25), 63.3% (38/60), 80.1% (238/297) and 85.7% (36 /42), respectively. The sensitivity, specificity, accuracy and AUC of the system for predicting HP infection was 89.6% (43/48), 61.8% (34/55), 74.8% (77/103), and 0.757, respectively. The diagnostic accuracy of the system was equivalent to that of endoscopist in diagnosing HP infection under white light (74.8% VS 72.1%, χ2=0.246, P=0.620). Conclusion:The system developed in this study shows noteworthy ability in evaluating HP status, and can be used to assist endoscopists to diagnose HP infection.

Objective:To assess the diagnostic efficacy of upper gastrointestinal endoscopic image assisted diagnosis system (ENDOANGEL-LD) based on artificial intelligence (AI) for detecting gastric lesions and neoplastic lesions under white light endoscopy.Methods:The diagnostic efficacy of ENDOANGEL-LD was tested using image testing dataset and video testing dataset, respectively. The image testing dataset included 300 images of gastric neoplastic lesions, 505 images of non-neoplastic lesions and 990 images of normal stomach of 191 patients in Renmin Hospital of Wuhan University from June 2019 to September 2019. Video testing dataset was from 83 videos (38 gastric neoplastic lesions and 45 non-neoplastic lesions) of 78 patients in Renmin Hospital of Wuhan University from November 2020 to April 2021. The accuracy, the sensitivity and the specificity of ENDOANGEL-LD for image testing dataset were calculated. The accuracy, the sensitivity and the specificity of ENDOANGEL-LD in video testing dataset for gastric neoplastic lesions were compared with those of four senior endoscopists.Results:In the image testing dataset, the accuracy, the sensitivity, the specificity of ENDOANGEL-LD for gastric lesions were 93.9% (1 685/1 795), 98.0% (789/805) and 90.5% (896/990) respectively; while the accuracy, the sensitivity and the specificity of ENDOANGEL-LD for gastric neoplastic lesions were 88.7% (714/805), 91.0% (273/300) and 87.3% (441/505) respectively. In the video testing dataset, the sensitivity [100.0% (38/38) VS 85.5% (130/152), χ2=6.220, P=0.013] of ENDOANGEL-LD was higher than that of four senior endoscopists. The accuracy [81.9% (68/83) VS 72.0% (239/332), χ2=3.408, P=0.065] and the specificity [ 66.7% (30/45) VS 60.6% (109/180), χ2=0.569, P=0.451] of ENDOANGEL-LD were comparable with those of four senior endoscopists. Conclusion:The ENDOANGEL-LD can accurately detect gastric lesions and further diagnose neoplastic lesions to help endoscopists in clinical work.

Objective:To construct a real-time artificial intelligence (AI)-assisted endoscepic diagnosis system based on YOLO v3 algorithm, and to evaluate its ability of detecting focal gastric lesions in gastroscopy.Methods:A total of 5 488 white light gastroscopic images (2 733 images with gastric focal lesions and 2 755 images without gastric focal lesions) from June to November 2019 and videos of 92 cases (288 168 clear stomach frames) from May to June 2020 at the Digestive Endoscopy Center of Renmin Hospital of Wuhan University were retrospectively collected for AI System test. A total of 3 997 prospective consecutive patients undergoing gastroscopy at the Digestive Endoscopy Center of Renmin Hospital of Wuhan University from July 6, 2020 to November 27, 2020 and May 6, 2021 to August 2, 2021 were enrolled to assess the clinical applicability of AI System. When AI System recognized an abnormal lesion, it marked the lesion with a blue box as a warning. The ability to identify focal gastric lesions and the frequency and causes of false positives and false negatives of AI System were statistically analyzed.Results:In the image test set, the accuracy, the sensitivity, the specificity, the positive predictive value and the negative predictive value of AI System were 92.3% (5 064/5 488), 95.0% (2 597/2 733), 89.5% (2 467/ 2 755), 90.0% (2 597/2 885) and 94.8% (2 467/2 603), respectively. In the video test set, the accuracy, the sensitivity, the specificity, the positive predictive value and the negative predictive value of AI System were 95.4% (274 792/288 168), 95.2% (109 727/115 287), 95.5% (165 065/172 881), 93.4% (109 727/117 543) and 96.7% (165 065/170 625), respectively. In clinical application, the detection rate of local gastric lesions by AI System was 93.0% (6 830/7 344). A total of 514 focal gastric lesions were missed by AI System. The main reasons were punctate erosions (48.8%, 251/514), diminutive xanthomas (22.8%, 117/514) and diminutive polyps (21.4%, 110/514). The mean number of false positives per gastroscopy was 2 (1, 4), most of which were due to normal mucosa folds (50.2%, 5 635/11 225), bubbles and mucus (35.0%, 3 928/11 225), and liquid deposited in the fundus (9.1%, 1 021/11 225).Conclusion:The application of AI System can increase the detection rate of focal gastric lesions.

OBJECTIVE: Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury. METHODS: PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments. RESULTS: Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1β and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3. CONCLUSION Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.

OBJECTIVE To establish the fingerprint of Sophora flavescens， and to screen differential components and determine their contents.　METHODS HPLC fingerprints of 12 batches of S. flavescens were established by using Similarity Evaluation System of Chromatographic Fingerprints of TCM （2012 edition）； common peaks were identified and their similarities were evaluated. Chemical pattern recognition analysis [cluster analysis （CA），principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）] were performed with SIMCA 14.1 and SPSS 23.0 software， and differential components which influenced the quality of S. flavescens were screen with variable importance in the projection（VIP）＞1 as standard. Meanwhile， the contents of 4 kinds of differential components were determined by the same HPLC method.　RESULTS There were 17 common peaks in the fingerprints of 12 batches of S. flavescens，and their similarities were all higher than 0.96. A total of 6 common peaks were identified， i.e. oxymatrine （peak 1）， oxysophocarpine （peak 2）， matrine （peak 10）， trifolirhizin （peak 14）， kurarinone （peak 16） and norkurarinone （peak 17）. Results of CA， PCA and OPLS-DA showed that 12 batches of S. flavescens were divided into 3 categories according to producing area， i.e. S1-S7 （Shangzhou District of Shaanxi Province） were grouped into one category， S8-S10 （Yichuan County of Henan Province） into one category and S11-S12 （Chifeng City of Inner Mongolia） into one category. VIPs of matrine， norkurarinone， kurarinone and oxysophocarpine and the chemical components represented by peak 11 and 9 were all greater than 1. The contents of matrine， norkurarinone， kurarinone and oxysophocarpine in 12 batches of S. flavescens were 2.65-4.93， 1.54-3.44， 9.63-12.94 and 5.08-6.10 mg/g， respectively. CONCLUSIONS HPLC fingerprint of S. flavescens is established successfully in the study， and can be used to screen 6 differential components by combining with chemical pattern recognition analysis， which can provide reference for quality control of S. flavescens.

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.
Animals ; Cell Differentiation ; Disease Models, Animal ; Ischemic Stroke ; Proteomics ; Rats ; Stem Cell Transplantation/methods* ; Stroke/therapy*

Objective:To explore the clinical value of procalcitonin (PCT) in predicting mortality of patients with acute biliary pancreatitis (ABP).Methods:The clinical data of 196 ABP patients admitted in the emergency department of Ruijin Hospital Affiliated to Shanghai Jiaotong University Medical College from January 2013 to June 2017 were analyzed retrospectively. The enrolled patients were divided into survival group ( n=176) and death group ( n=20) according to clinical outcome, and their clinical characteristics, laboratory results(including WBC, CRP, PCT), APACHEⅡ score, BISAP score, modified Marshall score, SOFA score and CTSI at admission were compared between two groups. The ROC curve and AUC were used to evaluate the effectiveness of PCT and multiple scoring systems in predicting mortality in ABP patients, and the Delong test was used to compare the predictive efficacy of various methods at 1-2 d, 3-4 d, and 5-7 d days after onset. Results:The PCT level, APACHEⅡ score, BISAP score, modified Marshall score, SOFA score, and CTSI of patients in the death group were significantly higher than those in the survival group [6.98(3.12, 13.64) μg/L vs 0.55(0.17, 1.74) μg/L, 12.00(6.00, 18.75) vs 6.00(3.00, 9.00), 3.20±1.47 vs 1.59±1.05, 2.85±0.37 vs 1.96±0.64, 5.50(4.00, 9.50) vs 2.00(1.00, 4.25), 5.05±2.33 vs 3.39±1.74], and all the differences were statistically significant (all P values <0.05). The AUC of PCT for predicting death was 0.881 (95% CI 0.820-0.938)and the cut-off value was 2.44. The predictive value of PCT was similar to that of the modified Marshall score, BISAP score and SOFA score, but higher than that of APACHEⅡ score and CTSI (all P values <0.05). The predictive AUC of PCT at 3-4 days after onset was higher than that of modified Marshall score, BISAP score and SOFA score, and were significantly higher than those at 1-2 days after onset. Conclusions:PCT can be used to predict the mortality of ABP within 7 days of onset. The predictive value of PCT was comparable to the modified Marshall score, BISAP score and SOFA score, and the best predictive time was 3-4 days after onset.

Objective:To investigate the expressions of TGF-β1,survivin and caspase-3 in hepatolithiasis-associated intrahepatic cholangiocarcinoma(ICC)tissue and their clinical significance.Methods:The expressions of TGF-β1,survivin and caspase-3 in intrahepatic bile duct specimens from 52 patients with intrahepatic stones and concomitant ICC(tumor group)and 30 patients with intrahepatic stones and chronic inflammation(inflammation group)as well as 30 specimens of normal intrahepatic bile duct were determined by immunohistochemical staining.The relations of the three factors with the clinicopathologic characteristics and prognosis of ICC patients were analyzed.Results:In tumor group,inflammation group and normal group,the positive expression rates TGF-β1 and survivin presented a successively decreasing order,while the positive expression rates of caspase-3 showed a successively increasing order(all P<0.05);in ICC tissue,the expressions of TGF-β1 and survivin showed a positive correlation(r=0.917,P<0.01),and both had a negative correlation with that of caspase-3(r=-0.890,P<0.01;r=-0.894,P<0.01).the results of univariate and multivariate analyses showed that TGF-β1,survivin and caspase-3 were independent influential factors for the prognosis of patients with hepatolithiasis-associated ICC(all P<0.05);the survival rates of patients with positive TGF-β1 or survivin expression were significantly reduced compared with respective negative ones(χ2=13.192,P=0.001;χ2=10.536,P=0.002),and the survival rate of patients with positive caspase-3 expression was significantly higher than those with its negative expression(χ2=5.469,P=0.023).Conclusion:The expressions of TGF-β1,survivin and caspase-3 are abnormal in hepatolithiasis-associated ICC tissue,and they may probably be jointly involved in the occurrence and development of this condition.