Quinic acid(QA)has antioxidant,anticancer and anti-inflammatory effects,but its pro-tective effect against bovine mastitis remains to be further investigated.The aim of this study was to investigate the inhibitory effects and mechanisms of quinic acid(QA)on lipopolysaccharide(LPS)-induced inflammation and pyroptosis in bovine mammary epithelial cells(MAC-T)and mouse mammary tissues.The CCK-8 method was applied to screen the treatment concentration of QA in MAC-T cells.The ELISA method was used to detect the expression levels of inflammatory factors,oxidative stress factors and pyroptosis indicators.The distribution of CD3 in mouse mam-mary tissues was detected by the immunohistochemical method.p65 nuclear translocation was measured by immunofluorescence.Western blot was performed to test the protein and phosphoryl-ation levels of NF-κB,the inflammasome of NOD-like receptor(NLRP3),Caspase-11 and gasder-min D(GSDMD).The results showed that QA(20,40 and 60 mg/L)significantly increased the activity of MAC-T cells(P＜0.05).QA treatment significantly reduced LPS-induced expression of inflammatory factors(TNF-α,IL-1β and IL 6),oxidative stress indicators(COX-2 and iNOS)and pyroptosis indicators(ROS,LDH and IL-18)in both MAC-T cells and mouse mammary tissues in a manner of dose-dependence(P＜0.05).Moreover,after intraperitoneal injection of QA at 5,10 and 20 mg/kg,respectively,the expression of T-lymphocyte marker CD3 induced by LPS was sig-nificantly downregulated in mouse breast tissues(P＜0.05).In addition,QA significantly de-creased the LPS-induced expression of NF-κB(IκBα,p65,p-IκBα and p-p65),inflammasome(NL-RP3,ASC and Caspase-1),Caspase-11 and DSDMD in both MAC-T cells and mouse mammary tis-sues,and inhibited p65 nuclear transfer in MAC-T cells(P＜0.05).Overall,the above results indi-cate that QA inhibits inflammatory response and pyroptosis through NF-κB and NLRP3 inflamma-some in both MAC-T cells and mouse mammary tissues.The results of this study provide novel da-ta on the prevention and treatment of mastitis by plant active ingredients.

To address the problems of the low accuracy of pathological classification caused by the large size of pathological data and the high cost of labeling,a pathological classification algorithm for oral cancer is designed based on multi-instance network and two-level attention module,which takes losses at the instance level and image block level into account.A retrospective analysis is conducted on 186 cases of oral cancer(126 cases of squamous cell carcinoma and 60 cases of adenocarcinoma)in the Department of Oral and Maxillofacial Surgery,the First Affiliated Hospital of Wannan Medical College,and the digital pathological sections are divided into training set,verification set and test set.The foreground and background segmentations are performed on the pathological image,and the noise is removed from the background.ResNet50 is used to extract features from the segmented pathological images,and the features are input into the first-level attention network to obtain the attention score and loss based on image block.Then,the image blocks are sorted according to the attention score,and the reset labels are input into the second-level attention network to obtain the loss based on the instance level.The loss of the two-level attention is taken as the total loss of the model,and the prediction result is obtained by training the final network.The experimental results show that the multi-instance network using two-level attention achieves an accuracy of 78.95%and AUC of 0.8430,demonstrating superior performance than the baseline models.

Objective:To evaluate whether additional radical surgery is necessary following non-curative endoscopic resection of early colorectal cancer.Method:Clinicopathological data in 104 patients following non-curative endoscopic resection of early colorectal coucer at the Department of General Surgery, Peking University First Hospital between Jan 2011 and Dec 2021.Results:Lymph node metastasis and/or residual cancer was found in 23 patients (22%), including 12 cases of lymph node metastasis, 7 cases of residual cancer and 4 patients with both residual cancer and lymph node metastasis. Univariate analysis indicated that vascular infiltration, positive vertical margin, and female gender were risk factors for lymph node metastasis. Risk factors for residual cancer were tumors ≥2 cm in size, negative lift sign, infiltration depth of ≥1 000 μm, and positive horizontal and vertical margins. Multivariate Logistic regression analysis revealed that vascular invasion, positive vertical margins, and being female were independent risk factors for lymph node metastasis, while positive vertical margins was independent risk factor for residual cancer. Salvage surgery lasted for a median of 184 (156-233) minutes, with an estimated blood loss of 50 (20-100) ml and an average postoperative hospital stay of 9 (8-11) days. Seven cases of Clavein-Dindo Ⅱ or higher complications were observed, including pulmonary embolism in 1 case , anastomotic leakage in one, lymphatic fistula in one, bowel obstruction in 2 cases and urinary tract infection in 2 cases.Conclusion:Salvage surgery is mandatory for early endoscopic non-curative resection of colorectal cancer.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To investigate the clinical effect of unilateral percutaneous vertebroplasty(PVP)combined with 3D printing technology for the treatment of thoracolumbar osteoporotic compression fracture.Methods A total of 77 patients with thoracolumbar osteoporotic compression fractures from October 2020 to April 2022 were included in the study,all of which were vertebral body compression fractures caused by trauma.According to different treatment methods,they were di-vided into experimental group and control group.Thirty-two patients used 3D printing technology to improve unilateral transpedicle puncture vertebroplasty in the experimental group,there were 5 males and 27 females,aged from 63 to 91 years old with an average of(77.59±8.75)years old.Forty-five patients were treated with traditional bilateral pedicle puncture vertebroplasty,including 7 males and 38 females,aged from 60 to 88 years old with an average of(74.89±7.37)years old.Operation time,intraoperative C-arm X-ray times,anesthetic dosage,bone cement injection amount,bone cement diffusion good and good rate,complications,vertebral height,kyphotic angle(Cobb angle),visual analogue scale(VAS),Oswestry disability index(ODI)and other indicators were recorded before and after surgery,and statistically analyzed.Results All patients were followed up for 6 to 23 months,with preoperative imaging studies,confirmed for thoracolumbar osteoporosis com-pression fractures,two groups of patients with postoperative complications,no special two groups of patients'age,gender,body mass index(BMI),time were injured,the injured vertebral distribution had no statistical difference(P＞0.05),comparable data.Two groups of patients with bone cement injection,bone cement dispersion rate,preoperative and postoperative vertebral body height,protruding after spine angle(Cobb angle),VAS,ODI had no statistical difference(P＞0.05).The operative time,intra-operative fluoroscopy times and anesthetic dosage were statistically different between the two groups(P＜0.05).Compared with the traditional bilateral puncture group,the modified unilateral puncture group combined with 3D printing technology had shorter operation time,fewer intraoperative fluoroscopy times and less anesthetic dosage.The height of anterior vertebral edge,kyphosis angle(Cobb angle),VAS score and ODI of the affected vertebrae were statistically different between two groups at each time point after surgery(P＜0.05).Conclusion In the treatment of thoracolumbar osteoporotic compression fractures,3D printing technology is used to improve unilateral puncture PVP,which is convenient and simple,less trauma,short operation time,fewer fluoroscopy times,satisfactory distribution of bone cement,vertebral height recovery and kyphotic Angle correction,and good functional improvement.

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

Objective:To investigate the application value of CT and MRI imageomics based on machine learning method in the diagnosis of pancreatic cancer.Methods:The clinical data of 62 patients with surgically resected and pathologically confirmed pancreatic cancer, who underwent enhanced CT scan, MRI plain or enhanced scan in Shanghai General Hospital between January 2014 and December 2021 were collected. According to the chronological order of surgery, 49 patients from January 2014 to December 2020 were enrolled in the training set and 13 patients from January 2021 to December 2021 were enrolled in the validation set. 3D-slicer 4.8.1 software was used to draw the region of interest in each layer of CT and MRI images for cancerous and paracancerous tissue segment. Image features were extracted by Python and the optimal feature set from the training set data was obtained by using Lasso regression model. The machine learning decision tree model was constructed. The receiver operating characteristic curve(ROC) curve was drawn, and the area under the curve (AUC) was calculated to evaluate the value of these three kinds of imageomics models in the diagnosis of pancreatic cancer.Results:The 1 767 CT features and 1 674 MRI features were obtained from enhanced CT scan, MRI plain scan and enhanced MRI scan, respectively. For the differential diagnosis model of cancerous tissue and paracancerous tissue, the enhanced CT scan data model obtained the optimal feature set involving 6 features, the MRI plain scan model obtained the optimal feature set involving 16 features, and the enhanced MRI scan model obtained the optimal feature set involving 15 features. The diagnostic model based on enhanced CT scan had an AUC of 0.98 in the training set and 1 in the verification group. The AUC of the MRI plain scan and enhanced MRI scan models in both the training set and the validation set was 1. The specificity and sensitivity of machine learning decision tree model based on the three kinds of imageomics models in the diagnosis of cancerous tissue and paracancerous tissue were 100%. For the differential diagnosis model of splenic artery wrapping, the enhanced CT scan model didn′t obtain the optimal features and had no diagnostic efficacy. The MRI plain scan model and enhanced MRI scan model obtained the optimal feature set involving 5 and 4 features, respectively. The AUC of the MRI plain scan model in the training set and the validation set were 0.862 and 0.750, respectively, with diagnostic sensitivity of 93.8% and 50.0%, and specificity of 78.6% and 100%, respectively. The AUC of the enhanced MRI scan model in the training set and the validation set were 0.950 and 0.861, respectively, with diagnostic sensitivity of 90.0% and 93.6%, and specificity of 100% and 78.6%, respectively.Conclusions:Based on the radiomics of CT enhanced, MRI plain scan and enhanced MRI scan, the machine learning diagnostic model has an accuracy of more than 90% in differentiating pancreatic cancer from paracancerous tissue. For the differentiation of splenic artery wrapping in pancreatic cancer, the diagnostic model based on enhanced MRI scan haS the best diagnostic efficiency.

Aim To study the effect of salidroside on the proliferation, migration, invasion and apoptosis of human highly metastatic liver cancer cells ( 97 H cells) . Methods Multifunctional cell analyzer was used to determine the effect of salidroside on the proliferation of 97H cells. Scratch assay was used to determine the effect of salidroside on the migration ability of 97H cells. Transwell assay was used to determine the effect of salidroside on the invasion ability of 97 H cells. Inverted microscope was used to observe the effect of salidroside on the morphology of 97H cells. Transmission electron microscope was employed to observe the effect of salidroside on mitochondria in 97 H cells. Flow cytometry was used to analyze the effect of salidroside on apoptosis and cycle distribution of 97 H cells. q-PCR was used to determine the effect of salidroside on related apoptosis genes in 97H cells.Western blot was used to determine the effect of salidroside on related migration, invasion and apoptosis proteins in 97H cells. Results Compared to blank group, salidroside treatment inhibited the proliferation, migration and invasion of 97H cells, and induced apoptosis of 97H cells. Salidroside could up-regulate the relative expression of Caspase-3 (P <0.05). Salidroside could up-regulate the levels of E-cad, Bax, Caspase-3 and Caspase-9 proteins (P <0.05), and down-regulate the levels of N-cad, Girdin and Bcl-2 proteins (P < 0. 05 ). Conclusions Salidroside has inhibitory effects on the proliferation, migration and invasion of 97H cells, and induces apoptosis of 97H cells through mitochondrial pathway.

Objective:To explore the neural mechanism of language dysfunction in patients with subacute stroke using functional near-infrared spectroscopy (fNIRS).Methods:Sixteen patients with non-fluent aphasia after subacute stroke (aphasia group), 16 patients with non-aphasia after stroke (non-aphasia group), and 16 healthy middle-aged and elderly subjects (control group) were enrolled into our study. The 6-min resting-state data of fNIRS were collected. Four language-related regions, Broca area, Wernicke area, dorso lateral prefrontal cortex (DLPFC), and supplementary motor area (SMA), were selected as regions of interest (ROIs), and the whole brain functional connection strength and functional connection strength in ROIs and between each two ROIs were analyzed by NirSpark software.Results:Compared with the control group (0.53±0.15) and non-aphasia group (0.47±0.12), the aphasia group had significantly decreased whole brain functional connection strength (0.29±0.14, P<0.05). Compared with the control group and non-aphasia group, the aphasia group had significantly decreased functional connection strength in the left Wernicke area, right Wernicke area, left Broca area, left SMA area, right SMA area and left DLPFC area ( P<0.05, FDR). Compared with the control group and non-aphasia group, the aphasia group had significantly decreased functional connection strength in the right Wernicke-left Wernicke area, right Wernicke-right Broca area, right Wernicke-left Broca area, right Wernicke-right DLPFC area, right Wernicke-left DLPFC area, right Wernicke-right SMA area, right Wernicke-left SMA area, left Wernicke-right Broca area, left Wernicke-left Broca area, left Wernicke-right DLPFC area, left Wernicke-left DLPFC, left Wernicke-right SMA area, left Wernicke-left SMA area, right Broca-left Broca area, right Broca-left DLPFC area, right Broca-right SMA area, right Broca-left SMA area, left Broca-right DLPFC area, left Broca-left DLPFC area, left Broca-right SMA area, left Broca-left SMA area, right DLPFC-left DLPFC area, right DLPFC-right SMA area, right DLPFC-left SMA area, left DLPFC-right SMA area, left DLPFC-left SMA area, and right SMA-left SMA area ( P<0.05, FDR). Conclusion:Abnormal functional connectivity strength of the whole brain and language-related key brain areas might be the neural mechanism of language dysfunction in patients with non-fluent aphasia after subacute stroke.

Objective: To explore a simple and feasible method for the isolation and purification of hepatocytes, hepatic stellate cells (HSC), and lymphocytes from mice. Methods: The cell suspension was obtained from male C57bl/6 mice by hepatic perfusion through the portal vein digestion method and then isolated and purified by discontinuous Percoll gradient centrifugation. Trypan blue exclusion was used to determine cell viability. Glycogen staining, cytokeratin 18, and transmission electron microscopy were used to identify hepatic cells. Immunofluorescence was used to detect α-smooth muscle actin combined with desmin in HSCs. Flow cytometry was used to analyze lymphocyte subsets in the liver. Results: After isolation and purification, about 2.7×10(7) hepatocytes, 5.7×10(5) HSCS, and 4.6×106 hepatic mononuclear cells were obtained from the liver of mice with a body weight of about 22g. The cell survival rate in each group was > 95%. Hepatocytes were apparent in glycogen deposited purple-red granules and cytokeratin 18. Electron microscopy showed that there were abundant organelles in hepatocytes and tight junctions between cells. HSC had expressed α-smooth muscle actin and desmin. Flow cytometry showed hepatic mononuclear cells, including lymphocyte subsets such as CD4, CD8, NKs, and NKTs. Conclusion: The hepatic perfusion through the portal vein digestion method can isolate multiple primary cells from the liver of mice at once and has the features of simplicity and efficiency.
Male ; Mice ; Animals ; Keratin-18 ; Actins ; Desmin ; Liver ; Hepatocytes ; Hepatic Stellate Cells