Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

ObjectiveTo reveal the effects of Huanglian Jiedutang （HLJDT） on the learning and memory abilities of APP/PS1 transgenic mice via hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） signaling pathway. MethodForty 5-month-old β-amyloid precursor protein （APP）/presenilin 1（PS1） mice were randomized into the model， donepezil （0.001 g·kg^-1·d^-1）， and low-， medium-， and high-dose （1.5， 3， 6 g·kg^-1·d^-1， respectively） HLJDT groups， and 8 C57BL/6 mice were taken as the normal group. After 45 days of continuous administration， Morris water maze test was conducted， and the organ indexes were calculated. The morphological structure of cerebral vascular endothelial cells in mice was observed under a transmission electron microscope. Western blot was employed to measure the protein levels of APP， HIF-1α， VEGF，VEGFA， and brain-derived neurotrophic factor （BDNF） in the hippocampus. The mRNA levels of APP， HIF-1α， and VEGF were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， the model group showed prolonged escape latency （P<0.05）， reduced distance and time around the target platform （P<0.05）， decrease brain and spleen indexes （P<0.05）， vascular endothelial cells with karyopyknosis and not abundant cytoplasm， up-regulated protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， down-regulated protein level of BDNF （P<0.05）， and up-regulated mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. Compared with the model group， high-dose HLJDT shortened the escape latency （P<0.05）， increased the distance and time around the target platform （P<0.05）， raised the brain and spleen indexes （P<0.05）， repaired the organelles of vascular endothelial cells， down-regulated the protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， up-regulated the protein level of BDNF （P<0.05）， and down-regulated the mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. ConclusionHLJDT can improve the learning and memory abilities of mice by reducing the expression of HIF-1α and VEGF， thus protecting the nerves.

This study aims to observe the effect of Panax notoginseng extracts on inflammatory re-sponse in immunosuppressed broilers and to investigate the mechanism through network pharma-cology and molecular docking combined with in vivo animal tests.Based on the TCMSP database and GeneCard and other disease databases,we searched for targets related to Panax notoginseng and broiler inflammation,screened key compounds and targets by applying Cytoscape 3.7.1 and String databases,respectively,and constructed a network relationship diagram of traditional Chi-nese medicine(TCM)-key components-targets,and carried out GO functional enrichment and KEGG pathway enrichment analyses by using the DAVID platform.The GO functional enrichment analysis and KEGG pathway enrichment analysis were carried out by the DAVID platform,visual-ized by the Chiplot online website,and finally,the core clustered proteins were analyzed by Pymol software to obtain the core targets,and molecular docking technology was used to predict the de-gree of matching between the active ingredients and the core targets as well as the animal experi-ments to further explore the pharmacological mechanism of Panax notoginseng extracts.Sixty 1-day-old red-feathered broilers were randomly divided into three groups(LPS group,CON group,and PN group),and the test period was 35 days.The LPS and PN groups were injected intraperito-neally with 250 μg/kg body weight of LPS,and the CON group was injected with an equal amount of sterile physiological saline on the 12,14,33,and 35 d.The LPS and PN groups were injected with 250 μg/kg body weight of LPS,and the CON group was injected with an equal amount of sterile physiological saline.The effect of Panax notoginseng extract on inflammatory cytokines in serum was detected by ELISA,and the hormone content in serum was also detected in each group,and fluorescence quantitative PCR was used to detect the effect of each group on the mRNA ex-pression levels of STAT3,IL-6,and CASP3.The results showed that the serum levels of IFN-γ,IL-6,iNOS,TNF-α,and TNF-β were significantly increased(P＜0.05),while the level of IL-10 was significantly decreased(P＜0.05)after LPS tapping at weeks 2 and 5.The serum levels of IFN-y,IL-6,iNOS,TNF-α,and TNF-β were significantly decreased(P＜0.05)and IL-10 was sig-nificantly increased(P＜0.05)by the addition of Panax ginseng extracts to the basal diet com-pared with the LPS group.Panax notoginseng extracts significantly decreased the serum levels of adrenocorticotropic hormone(ACTH)and corticosterone(CORT)(P＜0.05)and increased the levels of growth hormone(GH)(P＜0.05).A total of 8 active ingredients and 123 potential tar-gets for broiler inflammation were predicted by network pharmacology.The protective mechanism of Panax notoginseng against broiler inflammation may be related to the C-type lectin receptor(CLR)signaling pathway,Toll-like receptor(TLR)signaling pathway,MAPK signaling pathway,NOD-like receptor(NLR)signaling pathway,and FoxO signaling pathway.According to the pre-diction,the alleviation of inflammatory response in broiler chickens by Panax notoginseng may be related to the action on 12 key targets.Fluorescence quantitative PCR showed that Panax notogin-seng extract down-regulated the mRNA expression of IL-6 and CASP3(P＜0.05)and up-regula-ted that of STAT3(P＜0.05),and molecular docking results also showed that the active ingredi-ents in Panax notoginseng extracts could exert anti-inflammatory effects through IL-6 and CASP3.The results suggested that Panax quinquefolium extracts might alleviate the inflammatory response of immune-stressed broilers through multi-components,multi-targets,and multi-path-ways,and this study helps propose new therapeutic strategies and provides a theoretical basis for the development of feed additives based on Penthorum chinense Pursh extract.

Genkwa Fols, Kansui Radix, and Euphorbiae Pekinensis Radix in Shizao Decoction(SZD) are toxic to intestinal tract. Jujubae Fructus in this prescription can alleviate the toxicity, but the mechanism is still unclear. Therefore, this study aims to explore the mechanism. To be specific, 40 normal Sprague-Dawley(SD) rats were classified into the normal group, high-dose and low-dose SZD groups, and high-dose and low-dose SZD without Jujubae Fructus(SZD-JF) groups. The SZD groups were given(ig) SZD, while SZD-JF groups received the decoction without Jujubae Fructus. The variation of body weight and spleen index were recorded. The patho-logical changes of intestinal tissue were observed based on hematoxylin and eosin(HE) staining. The content of malondialdehyde(MDA) and glutathione(GSH) and activity of superoxide dismutase(SOD) in intestinal tissue were measured to evaluate the intestinal injury. Fresh feces of rats were collected to detect intestinal flora structure by 16S ribosomal RNA gene(16S rDNA) sequencing technology. The content of fecal short chain fatty acids and fecal metabolites was determined by gas chromatography-mass spectrometer(GC-MS) and liquid chromatography-mass spectrometer ultra-fast liquid chromatography-quadrupole-time-of-flight mass spectrometer(UFLC-Q-TOF-MS), separately. Spearman's correlation analysis was employed to analyze the differential bacteria genera and differential metabolites. RESULTS:: showed that high-dose and low-dose SZD-JF groups had high content of MDA in intestinal tissue, low GSH content and SOD activity, short intestinal villi(P<0.05), low diversity and abundance of intestinal flora, variation in the intestinal flora structure, and low content of short chain fatty acids(P<0.05) compared with the normal group. Compared with high-dose and low-dose SZD-JF groups, high-dose and low-dose SZD groups displayed low content of MDA in intestinal tissue, high GSH content and SOD activity, recovery of the length of intestinal villi, increased abundance and diversity of intestinal flora, alleviation of dysbacteria, and recovery of the content of short chain fatty acids(P<0.05). According to the variation of intestinal flora and fecal metabolites after the addition of Jujubae Fructus, 6 differential bacterial genera(Lactobacillus, Butyricimonas, Clostridia＿UCG-014, Prevotella, Escherichia-Shigella, Alistipes),4 differential short chain fatty acids(such as acetic acid, propionic acid, butyric acid, valeric acid) and 18 differential metabolites(such as urolithin A, lithocholic acid, and creatinine) were screened out. Beneficial bacteria such as Lactobacillus were in positive correlation with butyric acid and urolithin A(P<0.05). The pathogenic bacteria such as Escherichia-Shigella were in negative correlation with propionic acid and urolithin A(P<0.05). In summary, SZD-JF caused obvious intestinal injury to normal rats, which could lead to intestinal flora disorder. The addition of Jujubae Fructus can alleviate the disorder and relieve the injury by regulating intestinal flora and the metabolites. This study discusses the effect of Jujubae Fructus in relieving the intestinal injury caused by SZD and the mechanism from the perspective of intestinal flora-host metabolism, which is expected to serve as a reference for clinical application of this prescription.
Rats ; Animals ; Rats, Sprague-Dawley ; Propionates/pharmacology* ; Gastrointestinal Microbiome ; Fatty Acids, Volatile/pharmacology* ; Butyrates/pharmacology*

This study aims to explore the effects of chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar on the diversity of gut microbiota in the rat model of malignant ascites, identify the key differential microbial taxa, and reveal the biological mechanism of water-expelling effect of the two chemical ingredient groups. The rat model of malignant ascites induced by Walker-256 cells was established, and phenolphthalein was used as the positive drug. The rats were orally administrated with corresponding agents for consecutive 7 days. On day 6, fresh feces samples were collected from the rats, and 16 S rDNA high-throughput sequencing and GC-MS were employed to determine the composition of gut microbiota and the content of short-chain fatty acids, respectively. On day 7, serum and intestinal tissue samples were collected for the determination of related indicators. Compared with the control group, the model group showed decreased feces volume and urine volume(P<0.01), increased volume of ascites and levels of Na~+, K~+, and Cl~- in urine(P<0.01), down-regulated mRNA and protein levels of intestinal AQP8(P<0.01), lowered abundance of beneficial Lactobacillus(P<0.01) while risen abundance of potential pathogenic Lachnospiraceae and Anaeroplasma(P<0.01), and reduced content of short-chain fatty acids(P<0.01). Compared with the model group, administration with chemical ingredient groups B and C alleviated all the above indicators(P<0.01). In conclusion, chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar could alleviate the disordered gut microbiota in rats with malignant ascites to expel water through increasing the abundance of beneficial Lactobacillus and reducing the abundance of harmful Lachnospiraceae and Anaeroplasma. This study can provide a reference for the reasonable clinical application of Kansui Radix stir-fried with vinegar.
Acetic Acid/chemistry* ; Animals ; Ascites/drug therapy* ; Euphorbia/chemistry* ; Gastrointestinal Microbiome ; Plant Roots/chemistry* ; Rats

Objective:To investigate the influences of anxiety on postoperative efficacy in elderly patients with complex proximal humerus fractures.Methods:A retrospective case control study was conducted to analyze the clinical data of 297 elderly patients with complex proximal humerus fractures admitted to 5 tertiary hospitals in Shanghai from January 2017 to December 2018. There were 121 males and 176 females, aged 65-85 years [(74.2±8.5)years]. The fracture types included Neer type III in 176 patients and Neer type IV in 121 patients. Two days after admission, patients were analyzed by self-rating anxiety scale (SAS) and anxiety factors questionnaire (participated by Shanghai Mental Health Center) and they were divided into anxiety group (SAS>35) and nonanxiety group (SAS≤35). Anxiety group included 68 patients, among which 7 had conservative treatments. Nonanxiety group contained 229 patients, among which 7 had conservative treatments. Both groups underwent with proximal reduction of humerus fractures accepted the operations. Operative patient in both groups underwent open reduction and plate fixation. The surgery rate and length of hospital stay were compared between groups. After 1 year of follow-up, Constant-Murley score was used to evaluate the effect of shoulder joint and dual-energy X-ray absorptiometry (DXA) was taken to observe the wrist joint bone mineral density. Postoperative complications were recorded.Results:All operative patients were followed up for 10-28 months, with an average of 13.6 months. The surgery rate was 89.7% (61/68) in anxiety group and 96.9% (222/229) in nonanxiety group ( P<0.05). The hospital stay was (6.8±3.4)days for non-surgery patients and (10.2±2.8)days for surgery patients in anxiety group and (4.2±1.6)days for non-surgery patients and (7.4±2.2)days for surgery patients in nonanxiety group ( P<0.05). In anxiety group and nonanxiety group, the excellent and good rate of Constant-Murley score was respective 75.4% (46/61) and 88.3% (196/222) and the wrist joint bone mineral density was respective (-3.1±0.5)SD and (-2.9±0.6)SD (both P<0.05). The incidence of complications was 8.2% (5/61) in anxiety group and 4.5% (10/222) in nonanxiety group ( P>0.05). Conclusions:Anxiety has a significant negative influence on the surgery rate, length of hospital stay, shoulder joint function, wrist joint bone mineral density. Intervention on anxiety in elderly patients with complex proximal humerus fractures should be valued attention by clinical orthopedic surgeons.

Objective:To evaluate the safety and efficacy of combination of transjugular intrahepatic portosystemic shunt (TIPS) combined with interventional therapy for primary hepatic carcinoma complicated with portal hypertension.Methods:From October 2013 to December 2017, medical records of 141 patients with primary hepatic carcinoma complicated with portal hypertension hospitalized and treated in Anhui Provincial Cancer Hospital were collected. According to the inclusion and exclusion criteria, 32 cases were in the TIPS combined with interventional treatment group and 29 cases were included in the intervention-only group after age, gender, mean tumor diameter and Child-Pugh classification matched with TIPS combined with intervention treatment group. The efficacy of TIPS was obsented, and the related complications and prognosis of the two groups at six, 12 and 24 months after treatment were compared. Independent sample t test, Mann-Whitney U test and Chi-square test were used for statistical analysis, and Kaplan-Merier method was used for survival analysis. Results:There were no statistically significant differences between TIPS combined with intervention group and intervention-only group in age, gender, mean tumor diameter, Child-Pugh classification, Child-Turcotte-Pugh (CTP) score, Barcelona staging, interventional treatment, causes of liver cirrhosis, portal hypertension related symptoms , portal vein tumor thrombus, alanine aminotransferase (ALT), and total bilirubin (TBil) (all P>0.05). The success rate of TIPS of patients in TIPS combined with intervention group was 100% (32/32). All the portal hypertension related symptoms after TIPS were relieved, and the remission rate was 100% (32/32). Compared with that before TIPS, after TIPS, the portal vein pressure decreased ((36.5±6.9) cmH 2O vs. (25.5±5.6) cmH 2O (1 cmH 2O=0.098 kPa)), the diameter of portal vein decreased ((15.9±3.5) mm vs. (13.7±2.7) mm), and ascites volume decreased (abdominal circumference ((105.6±13.9) cm vs. (88.0±9.8) cm), red blood cell count ((2.6±0.8)×10 12/L vs. (3.3±1.3)×10 12 /L) and hemoglobin level ((78.9±15.5) g/L vs. (108.4±14.6) g/L) both increased, and the differences were statistically significant ( t=2.866, 3.105, 10.769, -3.548 and -3.869, all P<0.01). The stent patency rate six months after TIPS was 100% (32/32), the 12-month patency rate was 94% (30/32), and the 24-month patency rate was 84% (27/32). Six months, 12 months and 24 months after treatment, the incidence of ascites of patients in the TIPS combined with interventional treatment group was 0, 3.1% (1/32) and 9.4% (3/32), respectively, and the incidence of bleeding was 3.1% (1/32), 9.4% (3/32) and 15. 6% (5/32), respectively, which were all lower than those of the intervention-only group (13.8%, 4/29; 27.6%, 8/29; 65.5%, 19/29; 20.7%, 6/29; 34.5%, 10/29 and 62.1%, 18/29), and the differences were statistically significant ( χ2=4.72, 7.24, 20.80; and 4.62, 5.72, 13.97; all P<0.05). There were no statistically significant differences in the incidence rates of hepatic encephalopathy 6 and 12 months after treatment between the two groups (both P>0.05). The incidence of hepatic encephalopathy of intervention-only group (48.3%, 14/29) 24 months after treatment was higher than that of TIPS combined with intervention group (21.9%, 7/32), and the difference was statistically significant ( χ2=4.70, P=0.030). The results of Kaplan-Merier analysis indicated that 12 and 24 months after treatment the cumulative survival rates of TIPS combined with intervention group (84.4%, 27/32 and 53.1%, 17/32) were both higher than those of the intervention-only group (41.4%, 12/29 and 13.8%, 4/29), and the differences were statistically significant ( χ2=12.20 and 5.06, both P<0.05). The median survival time of TIPS combined with intervention group was 25 months, which was longer than that of the intervention-only group (12 months), and the difference was statistically significant ( Z=3.341, P=0.001). Conclusions:TIPS combined with interventional therapy is safe and effective in the treatment of primary hepatic carcinoma complicated with portal hypertension, which can improve the quality of life and increase the survival rate.

Objective To evaluate the efficacy of transjugular intrahepatic portosystemic shunt (TIPS)in the treatment of patients with hepatic sinusoidal obstruction syndrome (HSOS).Methods From April 2015 to August 2018,at The First Affiliated Hospital of University of Science and Technology of China,21 patients with gynura segetum caused HSOS were selected.All the patients received TIPS treatment because of unresponsiveness to anticoagulant therapy for at least two weeks.After operation patients were followed up with liver and portal vein Doppler ultrasonography examination,liver and kidney function tests,and survival observation.T test,logistic univariate regression analysis and Cox regression analysis were performed for statistical analysis.Results Among the 21 patients with gynura segetum-related HSOS,18 patients were in the subacute phase and three patients in the chronic phase.All of them were moderate or severe patients and all successfully underwent TIPS.The postoperative portal vein pressure was (16.71 ± 4.68) cmH2O (1 cmH2O =0.098 kPa),which was lower than that before operation ((41.52 ±6.27) cmH2O),and the difference was statistically significant (t =16.936,P ＜ 0.01).The postoperation portal vein blood flow velocity was (41.52 ±7.70) cm/s,which was higher than before operation ((11.19 ± 3.29) cm/s),and the difference was statistically significant (t =-15.191,P ＜0.01).At one month after operation,15 of 21 patients were clinically cured;among the remaining six patients,four patients were improved and two patients were ineffective (including one patient died).At four months after operation,two patients died,and the remaining 19 patients were clinically cured.At one month after operation,the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),total bilirubin (TBil) and serum creatinine were (23.7 ± 16.8) U/L,(33.9 ±7.4) U/L,(52.7 ± 38.2) μmol/L and (62.7 ± 12.6) μmol/L,respectively,which were lower than those before operation ((60.5 ± 42.4) U/L,(78.4 ± 42.4) U/L,(74.9 ± 38.2) μmol/L and (82.4 ± 19.6) μmol/L,respectively),and the differences were statistically significant (t =3.193,3.493,2.378 and 4.519;all P ＜ 0.05).The level of albumin was (39.0 ±3.1) g/L,which was higher than that before operation ((30.9 ± 3.8) g/L),and the difference was statistically significant (t =-10.283,P ＜ 0.01).Portal vein thrombosis and preoperative TBil level had predictive value for therapeutic efficacy (both P ＜0.05).The one-year cumulative survival rate of patients was 90.5％.Preoperative TBil level and hepatic encephalopathy had effects on the prognosis of patients (both P ＜ 0.05).Conclusion TIPS is a safe,reliable and effective treatment for patients with subacute and chronic gynura segetum-related HSOS who are not responding to ineffective anticoagulant therapy,which can improve the prognosis and survival rate of the patients.

Brain ; pathology ; China ; Humans ; Organ Preservation ; standards ; Tissue Banks ; ethics ; standards

Objective To discuss the technical method,safety and clinical efficacy of CT-guided 125I radioactive seed implantation for the treatment of mediastinal lymph node metastases.Methods CT-guided 125I radioactive seed implantation was carried out in 11 patients with mediastinal lymph node metastases.Before 125I seed implantation,the interstitial brachytherapy treatment planning system (TPS) was employed to formulate a treatment plan.The particles with radioactivity of (1.11-2.96) × 107Bq (0.3-0.8 mCi) were used for the implantation.Postoperative complications were recorded.The local lesion control rate and the effective rate of pain relief were evaluated at one,3,6 and 12 months after 125I seed implantation.Results After 125I seed implantation,pneumothorax occurred in 3 patients,tracheal fistula in one patient,and pulmonary infection in one patient.The local lesion control rates at one,3,6 and 12 months were 81.8％,90.9％,72.7％ and 72.7％ respectively;the effective rate of pain relief at one week,one,3,6 and 12 months were 100％,90.9％,90.9％,81.8％ and 72.7％ respectively.Conclusion For the treatment of mediastinal lymph node metastases,CT-guided radioactive 125I seed implantation is less-invasive with less complications,and it carries reliable local lesion control rate.Therefore,this technique is a safe therapeutic means.