Role of SIRTl/Nrf2/HO-l pathway in attenuation of learning and memory impairment by sevoflurane postcondition in a mouse model of hemorrhagic shock and resuscitation / 中国药理学通报

Aim To explore the role of SIRT1/Nrf2 / HO-1 in alleviating the cognitive function impairment by sevoflurane treatment in a mouse model of postoperative cerebral reperfusion. Methods C57BL/6J mice were randomly divided into five groups: sham operation group, hemorrhagic shock reperfusion group, sevoflurane postconditioning group, sevoflurane postcondition-ing + SIRT1 inhibitor group and sevoflurane postconditioning + Nrf2 inhibitor group. Mice were subjected to Morris water maze test after cerebral ischemia reperfusion. The ATP, superoxide dismutase (SOD), ROS and MDA contents in tissue of mice were detected. SIRT1, Nrf2 and HO-1 proteins in tissue were detected by Western blot. Results After hemorrhagic shock, the learning and memory ability of mice was reduced.ATP and SOD concentration in hippocampus was reduced , MDA and ROS concentration increased, and the SIRT, Nrf2 and HO-1 concentration was reduced. Sevoflurane improved the cognitive dysfunction and oxi-dative damage in postoperative mice, and the neuro-protective effect of sevoflurane on hemorrhagic shock and resuscitation mice was weakened followed with SIRT1 and Nrf2 inhibitors. Conclusion Sevoflurane probably alleviates the oxidative reaction damage and cognitive impairment caused by cerebral reperfusion in mice through SIRT1/Nrf2/H0-1 pathway.

Change trend and prediction of lung cancer mortality in Suzhou in 2001-2020 / 公共卫生与预防医学

Objective To explore the epidemiological characteristics and trend of lung cancer mortality in Suzhou, to predict the future lung cancer mortality by ARIMA model, and to provide a scientific basis for the research of lung cancer prevention and control strategy. Methods The annual change percentage (APC) was used to analyze the annual change trend of lung cancer mortality from 2001 to 2020, and the ARIMA optimal model was employed to predict the lung cancer mortality from 2021 to 2025. Results The average annual crude mortality of lung cancer in Suzhou from 2001 to 2020 was 46.45/100 000, while the standardized mortality was 23.51/100 000. In recent 20 years, the crude mortality showed an upward trend and the standardized mortality showed a downward trend (APC crude rate = 2.51%, APC standardized rate = -0.78% , P < 0.001). The standardized mortality of lung cancer in men was 3.22 times that in women. The mortality of lung cancer in people over 45 years old increased with the increase of age, but the mortality in the 30-59 years old group showed a downward trend year by year. ARIMA model predicted that the annual trend of lung cancer crude mortality will tend to be flat in the next five years. Conclusion The crude mortality rate of lung cancer in Suzhou shows an upward trend, while the standardized mortality rate decreases year by year, suggesting that we should pay attention to the prevention and control of lung cancer in the elderly, accurately identify high-risk population of lung cancer, promote health publicity and education, carry out lifestyle intervention, and popularize the early screening of lung cancer.

The edification of Japanese nutrition health educators degree system on the promotion of nutrition and health education in schools in China / 中国学校卫生

Abstract@#Through in-depth investigation into Japanese nutrition health educators post content, configuration, training mode, advanced education practice and the difficulties, the paper explores the effective ways of integrating nutrition health education into the school health education teacher and curriculum system as well as health promotion, so as to guide teachers and students to establish a correct concept of health, enhance health literacy and develop a healthy lifestyle. Additionally, the paper aims at providing suggestions for the construction of nutrition and health school as well as the future development of nutrition health education in China.

Research progress in bioanalysis and pharmacokinetics of liposome nanomedicine / 药学学报

Liposome nanomedicine is a new drug preparation with nano scale, which is encapsulated by lipid bilayer vesicle structure. As a drug delivery carrier, liposome has many advantages such as good biocompatibility, biodegradation in vivo and strong targeting. The application of liposome nano drug delivery system can improve the pharmacokinetic behavior and efficacy of some drugs in vivo to a certain extent, and reduce toxic and side effects. After liposome nanomedicine enter into the body, free drugs will be released, so there will be loaded drugs and free drugs in the body. Loaded drugs are drug repositories, free drugs are related to their efficacy and adverse reactions. Therefore, the pharmacokinetics study of liposomes should focus on both loaded drugs and free drugs. Quantitative analysis of free drugs, liposome particles and their materials is a big challenge. The bioanalysis and pharmacokinetics of liposome nanomedicines will be introduced and discussed in this review. We hope this review will provide a reference for the development of liposome nanomedicine.

Effect of different courses of Budesonide on endoscopic dacryocystorhinostomy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the effect of different courses of budesonide nasal spray on the postoperative efficacy of endoscopic dacryocystorhinostomy.METHOD: Prospective study. A total of 90 patients(90 eyes)with chronic dacryocystitis who underwent endoscopic dacryocystorhinostomy in our hospital from January 2019 to April 2022 were selected, and they were randomly divided into three groups. In group A, 30 patients(30 eyes)continued to use budesonide nasal spray for 2mo after surgery; in group B, 30 patients(30 eyes)continued to use budesonide nasal spray for 3mo after surgery; in group C, 30 patients(30 eyes)continued to use budesonide nasal spray for 4mo after surgery. Follow-up for 6mo after surgery, Lund-Kenndey score, surgical efficacy and complications of the three groups were compared.RESULT: At 3, 4 and 6mo after surgery, the Lund-Kenndey score of group C was lower than that of group A(P&#x003C;0.05), and there was no statistical difference between group C and group B(P&#x003E;0.05). Following up to 6mo, the surgical efficacy of group C was better than that of group A, and the incidence of complications was lower than that of group A(P&#x003C;0.05); There was no statistically significant difference in efficacy and complications between group C and group B(P&#x003E;0.05).CONCLUSION: Budesonide combined with endoscopic dacryocystorhinostomy has acceptable efficacy in the treatment of chronic dacryocystitis. After 3mo of treatment, inflammation can be well controlled, which can reduce the occurrence of postoperative complications and improve the effective rate of surgery. However, increasing the treatment course cannot further improve the effective rate of surgery.

Alterations of macular ganglion cell layer thickness and optic disc parameters in patients with early diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the changes of optic disc parameters, peripapillary retinal nerve fibers layer(pRNFL)thickness and macular ganglion cell layer(mGCL)thickness among patients with early diabetes retinopathy and healthy controls by Cirrus HD-optical coherence tomography(OCT).METHODS: In this cross-sectional comparative study, 45 non-diabetic retinopathy(NDR), 52 mild nonproliferative diabetic retinopathy(NPDR), 55 moderate NPDR with type 2 diabetes mellitus(T2DM)and 64 age-matched healthy controls were included. The fasting blood glucose(FBG), duration of diabetes, glycosylated hemoglobin(HbA1c)and past history of the patients were collected in detail. Optic disc parameters(i.e., binocular RNFL thickness symmetry percentage, rim area, optic disc area, cup-to-disc ratio, cup volume), pRNFL thickness and mGCL thickness were measured by Cirrus HD-OCT. The comparison of different groups was performed by one-way analysis of variance.RESULTS: Compared with the control group, the binocular RNFL thickness symmetry percentage and rim area were significantly decreased, while the average C/D and vertical C/D were significantly increased in the NDR group, mild NPDR group and moderate NPDR group(all P&#x003C;0.05). Compared with the control group, the peripapillary RNFL thicknesses(superior, temporal, inferior, nasal)and macular GCL thickness(average, minimum, superior, supero-temporal, infero-temporal, inferior, supero-nasal, and infero-nasal)became thinner in the NDR group, mild NPDR group, and moderate NPDR group(all P&#x003C;0.05).CONCLUSION: Patients with early DR have significantly decreased binocular RNFL thickness asymmetry, rim area, pRNFL and mGCL thickness, while they have significantly increased cup-to-disc ratio when compared to healthy controls. The results support the statement that DM causes inner retinal neurodegenerative changes even in T2DM patients without overt microangiopathy.

Research progress on the application of deep learning in choroidal segmentation / 国际眼科杂志(Guoji Yanke Zazhi)

In recent years, ophthalmology, as one of the medical fields highly dependent on auxiliary imaging, has been at the forefront of the application of deep learning algorithm. The morphological changes of the choroid are closely related to the occurrence, development, treatment and prognosis of fundus diseases. The rapid development of optical coherence tomography has greatly promoted the accurate analysis of choroidal morphology and structure. Choroidal segmentation and related analysis are crucial for determining the pathogenesis and treatment strategies of eye diseases. However, currently, choroidal mainly relies on tedious, time-consuming, and low-reproducibility manual segmentation. To overcome these difficulties, deep learning methods for choroidal segmentation have been developed in recent years, greatly improving the accuracy and efficiency of choroidal segmentation. The purpose of this paper is to review the features of choroidal thickness in different eye diseases, explore the latest applications and advantages of deep learning models in measuring choroidal thickness, and focus on the challenges faced by deep learning models.

Three-dimensional visualization on the relationship between tubules after macula densa and afferent arterioles in mouse kidney / 解剖学报

Objective To establish the spatial course of distal tubule and afferent arterioles after macula densa, and to locate and detect the proteins in the adjacent parts by using three-dimensional visualization technology of microstructure. Methods C57 BL/6J mice were fixed by perfusion and embedded in epon 812. Tissue blocks were cut perpendicular to the longitudinal axis of the kidney. And a total of 720, 2. 5 μm-thick consecutive sections were obtained from the renal capsule to the outer stripe of the renal outer medulla. After aligning the digital microscopic images through computer registration procedures, the tubules and vessels were traced by 3D reconstruction program edited by C Language. Selecting the tissue sections of the contact site and applying the improved immunoperoxidase staining method to detect H

Research progress of endothelial-mesenchymal transdifferentiation in fibrotic diseases / 中国药理学通报

Fibrosis is a repair response initiated by tissues and organs after injury, and is a self-protection mechanism of the body. It has been found that endothelium-to-interstitial transdifferentiation (EndMT) is involved in the physiological and pathological processes of various organ fibrosis, which has become a focus of the research on fibrotic diseases. In recent years, the study has found that EndMT plays an important role in many pathological processes in cardiovascular system, lungs, kidneys, liver, pancreas fibrosis, and so on. This article summarizes EndMT regulatory mechanism and its role in each organ fibrosis, as well as the related treatment progress of EndMT targets, so as to provide new targets for prevention and control of organ fibrosis.

Study on preventive and therapeutic effect of Tongbu-fangchan prescription on Ach-CaCl / 中国药理学通报

Aim To explore he preventive and therapeutic effects of Tongbu-fangchan prescription on aceylcholine-calcium chloride (Ach-CaCl

Effects of different extraction parts of Tibetan medicine Pulicaria insignis Drumm ex Dunn on CIA rats / 中国药理学通报

Aim To clarify the anti-rheumatoid arthritis effect of Tibetan medicine Pulicaria insignis (P. insignis),sift out the active parts against rheumatoid arthritis,and investigate the mechanism. Methods Rat rheumatoid arthritis (CIA) model was established with bovine type II collagen and incomplete Freund's adjuvant. The effects of the total extract of P. insignis, macroporous resin eluted parts with different concentrations of ethanol and Tripterygium Glycosides (GTW) on the degree of foot swelling in CIA rats were observed,the levels of tumor necrosis factor (TNF-α), intd rheumaerleukin-1β (IL-1β) antoid factor (RF) in serum of rats were detected, the pathological changes of synovial tissues were investigated, and the effects on MAPK/p38/NF-κB, TLR4/NF-κB protein expressions were explored by Western blot. Results Compared with the model group, the total extract of P. insignis and the eluted part of macroporous resin 60% ethanol could significantly reduce the degree of joint swelling in CIA rats, effectively improve the pathological changes of rats synovium tissues, and significantly reduce the levels of rat tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and rheumatoid factor (RF) in serum inflammatory factors, and markedly decrease the expression of related inflammatory proteins (TLR4, NF-κB, Myd88, p-p38, p-IκBα, iNOS, etc) in synovial tissue. Conclusions (1) P. insignis can relieve the symptoms of joint inflammation in rats with rheumatoid arthritis, and the eluted part of macroporous resin 60% ethanol of P. insignis is the effective active part for anti-rheumatoid arthritis. (2) The total and partial extracts of P. insignis can relieve arthritis symptoms in CIA rats through inhibiting the MAPK/ p38/NF-κB and TLR4/NF-κB signaling pathways.

Mechanism of Gardeniae Fructus in ameliorating rheumatoid arthritis based on metabolomics and intestinal microbiota / 中国中药杂志

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.

Mechanism of Marsdenia tenacissima against ovarian cancer based on network pharmacology and experimental verification / 中国中药杂志

The present study aimed to explore the main active components and underlying mechanisms of Marsdenia tenacissima in the treatment of ovarian cancer(OC) through network pharmacology, molecular docking, and in vitro cell experiments. The active components of M. tenacissima were obtained from the literature search, and their potential targets were obtained from SwissTargetPrediction. The OC-related targets were retrieved from Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man(OMIM), GeneCards, and PharmGKB. The common targets of the drug and the disease were screened out by Venn diagram. Cytoscape was used to construct an "active component-target-disease" network, and the core components were screened out according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened out according to the node degree. GO and KEGG enrichment analyses of potential therapeutic targets were carried out with DAVID database. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock. Finally, the anti-OC activity of M. tenacissima extract was verified based on SKOV3 cells in vitro. The PI3K/AKT signaling pathway was selected for in vitro experimental verification according to the results of GO function and KEGG pathway analyses. Network pharmacology results showed that 39 active components, such as kaempferol, 11α-O-benzoyl-12β-O-acetyltenacigenin B, and drevogenin Q, were screened out, involving 25 core targets such as AKT1, VEGFA, and EGFR, and the PI3K-AKT signaling pathway was the main pathway of target protein enrichment. The results of molecular docking also showed that the top ten core components showed good binding affinity to the top ten core targets. The results of in vitro experiments showed that M. tenacissima extract could significantly inhibit the proliferation of OC cells, induce apoptosis of OC cells through the mitochondrial pathway, and down-regulate the expression of proteins related to the PI3K/AKT signaling pathway. This study shows that M. tenacissima has the characteristics of multi-component, multi-target, and multi-pathway synergistic effect in the treatment of OC, which provides a theoretical basis for in-depth research on the material basis, mechanism, and clinical application.

Scientific basis of acupuncture on mesenchymal stem cells for treating ischemic stroke / 中国针灸

The scientific basis of acupuncture on mesenchymal stem cells (MSCs) for treating ischemic stroke (IS) is discussed. MSCs transplantation has great potential for the treatment of tissue damage caused by early stage inflammatory cascade reactions of IS, but its actual transformation is limited by various factors. How to improve the homing efficiency of MSCs is the primary issue to enhance its efficacy. As such, the possible mechanisms of acupuncture and MSCs transplantation in inhibiting inflammatory cascade reactions induced by IS are explored by reviewing literature, and a hypothesis that acupuncture could promote the secretion of stromal cell-derived factor-1α (SDF-1α) from ischemic foci to regulate SDF-1α/CXC chemokine receptor 4 (CXCR4) axis, thereby improving the homing efficiency of MSCs transplantation, exerting its neuroprotective function, and improving the bed transformation ability, is proposed.

Plastic and reconstruction surgery for non-healing wound after posterior spinal surgery / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical significance of different plastic surgeries in the treatment of poor healing wound after posterior spinal internal fixation.@*METHODS@#In this study, 16 patients with poor incision healing after posterior spinal internal fixation were retrospectively included, and dif-ferent plastic surgery treatment plans were determined according to the wound characteristics and defect condition. The measures included debridement, vacuum sealing drainage (VSD), and different tissue flaps according to the location and extent of the defect.@*RESULTS@#A total of 16 patients meeting the criteria were included, of whom 3 were treated with debridement combined with VSD and wound suture directly, 6 were treated with debridement combined with Z-flap for wound repair, 1 was treated with bilateral sacrospinous muscle flap for dural defect repair combined with Z-flap for skin wound repair, 1 was treated with lectus dorsi flap for wound repair, 3 were treated with the fourth lumbar artery perforator flap for wound repair. The wound was repaired with local rotating flap in 1 case and gluteus maximus musculocutaneous flap in 1 case. Among the 16 patients, 7 cases were positive for wound culture, including 3 cases of Staphylococcus aureus, 1 case of Pseudomonas aeruginosa, 1 case of Staphylococcus epidermidis, 1 case of Escherichia coli, 1 case of Klebsiella pneumoniae, and the other 9 cases were negative. After surgery, there were 7 patients with different degrees of poor wound healing, including 3 patients undergoing dressing change, 2 patients undergoing secondary debridement and suture, 1 patient undergoing free scalp skin graft, and 1 patient undergoing local effusion suction treatment. All the above 7 patients were discharged from hospital after improvement, and the remaining 9 patients had good first-stage wound hea-ling after surgery. None of the 16 patients underwent internal fixation.@*CONCLUSION@#Multiple factors could lead to poor wound healing after posterior spinal internal fixation. Early intervention, thorough debridement, removal of necrotic/infected tissue, and selection of suitable skin flap for effective wound fil-ling and covering were important means to ensure wound healing after spinal surgery and reduce removal of internal fixation.

The impact of amygdala glutamate receptors on cardiovascular function in rats with post-traumatic stress disorder / 生理学报

Post-traumatic stress disorder (PTSD) has been reported to be associated with a higher risk of cardiovascular disease. The amygdala may have an important role in regulating cardiovascular function. This study aims to explore the effect of amygdala glutamate receptors (GluRs) on cardiovascular activity in a rat model of PTSD. A compound stress method combining electrical stimulation and single prolonged stress was used to prepare the PTSD model, and the difference of weight gain before and after modeling and the elevated plus maze were used to assess the PTSD model. In addition, the distribution of retrogradely labeled neurons was observed using the FluoroGold (FG) retrograde tracking technique. Western blot was used to analyze the changes of amygdala GluRs content. To further investigate the effects, artificial cerebrospinal fluid (ACSF), non-selective GluR blocker kynurenic acid (KYN) and AMPA receptor blocker CNQX were microinjected into the central nucleus of the amygdala (CeA) in the PTSD rats, respectively. The changes in various indices following the injection were observed using in vivo multi-channel synchronous recording technology. The results indicated that, compared with the control group, the PTSD group exhibited significantly lower weight gain (P < 0.01) and significantly decreased ratio of open arm time (OT%) (P < 0.05). Retrograde labeling of neurons was observed in the CeA after microinjection of 0.5 µL FG in the rostral ventrolateral medulla (RVLM). The content of AMPA receptor in the PTSD group was lower than that in the control group (P < 0.05), while there was no significant differences in RVLM neuron firing frequency and heart rate (P > 0.05) following ACSF injection. However, increases in RVLM neuron firing frequency and heart rate were observed after the injection of KYN or CNQX into the CeA (P < 0.05) in the PTSD group. These findings suggest that AMPA receptors in the amygdala are engaged in the regulation of cardiovascular activity in PTSD rats, possibly by acting on inhibitory pathways.

Multi-component content determination of Dracocephalum tanguticum by quantitative analysis of multi-components by single-marker / 中国中药杂志

This study aims to establish a method for the simultaneous determination of 7 active components in Dracocephalum tanguticum and to evaluate the quality of medicinal materials from different habitats. The method was established with high performance liquid chromatography(HPLC) and the gradient elution was performed with the mobile phase of acetonitrile-methanol-0.2% phosphoric acid solution at a column temperature of 35 ℃, an injection volume of 15 μL, and a flow rate of 0.6 mL·min~(-1). The detection wavelength was set as 215 nm. With rosmarinic acid as the internal reference, the relative correction factors and the content of other 6 components were calculated. The results were compared with those obtained with the external standard method. The results showed that the samples from Huangzhong county, Qinghai province had the best quality, with the highest content of p-hydroxybenzoic acid, cosmosiin, rosmarinic acid, oleanolic acid, and ursolic acid(9.29, 12.14, 6.02, 3.11, 17.67 mg·g~(-1) respectively). The samples from Chaya county, Tibet autonomous region ranked the second, with the highest content of betulin and betulinic acid(15.53, 7.17 mg·g~(-1), respectively). The method is accurate, reliable, and repeatable and suitable for the simultaneous determination of multiple components in D. tanguticum. The content of functional components varied in the samples from different producing areas and can be used as the indicator for the quality evaluation of medicinal materials.

Heixiaoyao Powder interferes with microglia polarization in AD model mice by regulating NOX2/ROS/NF-κB signaling pathway / 中国中药杂志

The effect and mechanism of Heixiaoyao Powder on the polarization of microglia(MG) in APP/PS1 double transgenic mice were explored based on NADPH oxidase 2(NOX2)/reactive oxygen species(ROS)/nuclear factor kappaB(NF-κB) signaling pathway. Fifty 4-month-old male APP/PS1 mice were randomly divided into a model group, an MCC950 group(10 mg·kg~(-1)), and low-, medium-, and high-dose Heixiaoyao Powder groups(6.45, 12.89, and 25.78 g·kg~(-1)). Thirty male C57BL/6J mice of the same age and strain were randomly divided into a blank group, a blank + intragastric intervention group, and a blank + intraperitoneal injection group. Drug intervention lasted 90 days. Morris water maze test was used to detect learning and cognitive ability. Nissl staining and transmission electron microscopy were used to observe the pathological morphology and ultrastructure of hippocampal neurons. Immunofluorescence was used to detect the positive expression of M1-type marker CD16/32~+/Iba-1~+, M2-type marker CD206~+/Iba-1~+ of MG and the expression of hippocampal ROS. The colorimetric method was used to detect the content of malondialdehyde(MDA) and superoxide dismutase(SOD) in the hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory factors, including interleukin-6(IL-6), interleukin-8(IL-8), and tumor necrosis factor-α(TNF-α), in the hippocampus. Western blot was used to detect the protein expression of β-amyloid protein(Aβ), Iba-1, CD16/32, CD206, NOX2, NF-κB, p-NF-κB, NF-κB inhibitor alpha(IκBα), and p-IKBα in the hippocampus. The results showed that as compared with the blank group, the model group showed prolonged target quadrant movement distance and escape latency(P<0.01), shortened target quadrant retention time and percentage(P<0.01), disorganized neuronal cells with swelling, nuclear disappearance or bias, reduced number of cells, dissolved or absent Nissl bodies, and a clear area in the cytoplasm, damaged and shrunk cell membrane with abnormal cell morphology, few organelles in the cytoplasm, reduced and swollen mitochondria, increased MG M1-type marker CD16/32~+/Iba-1~+(P<0.01), decreased M2-type marker CD206~+/Iba-1~+(P<0.01), increased ROS activity and MDA content(P<0.01), decreased SOD level(P<0.01), elevated inflammatory factors IL-6, IL-8, and TNF-α(P<0.01), up-regulated protein expression and phosphorylation of Aβ, CD16/32, Iba-1, NOX2, NF-κB, and IKBα(P<0.01), and down-regulated CD206(P<0.01). There was no statistically significant difference between the blank group, the blank + intragastric intervention group, and the blank + intraperitoneal injection group. After the intervention of Heixiaoyao Powder, the Heixiaoyao Powder groups showed shortened target quadrant movement distance and escape latency(P<0.01), prolonged target quadrant retention time and percentage(P<0.01), increased and neatly arranged cells with relieved swelling, increased Nissl bodies, regular cell morphology, and intact cell membrane, relieved swelling of mitochondria, slightly expanded endoplasmic reticulum, decreased CD16/32~+/Iba-1~+(P<0.05 or P<0.01), increased CD206~+/Iba-1~+(P<0.01), decreased ROS activity and MDA content(P<0.01), increased SOD level(P<0.01), decreased content of inflammatory factors IL-6, IL-8, and TNF-α(P<0.01), down-regulated protein expression and phosphorylation of Aβ, CD16/32, Iba-1, NOX2, NF-κB, and IKBα(P<0.01), and up-regulated CD206(P<0.01). In conclusion, Heixiaoyao Powder can alleviate neuronal damage and improve the learning and memory abilities of APP/PS1 mice. The mechanism of action may be related to the inhibition of NOX2/ROS/NF-κB signaling pathway, regulating the polarization of MG, increasing the expression of M2 type, inhibiting the expression of M1 type, and reducing the release of inflammatory factor.

Antimicrobial resistance and plasmid-mediated colistin resistance mechanism of diarrheagenic Escherichia coli recovered from foods in parts of China in 2020 / 中华预防医学杂志

Objective: To investigate the antimicrobial resistance of food-borne diarrheagenic Escherichia coli (DEC) and the prevalence of mcr genes that mediates mobile colistin resistance in parts of China, 2020. Methods: For 91 DEC isolates recovered from food sources collected from Fujian province, Hebei province, Inner Mongolia Autonomous Region and Shanghai city in 2020, Vitek2 Compact biochemical identification and antimicrobial susceptibility testing platform was used for the detection of antimicrobial susceptibility testing (AST) against to 18 kinds of antimicrobial compounds belonging to 9 categories, and multi-polymerase chain reaction (mPCR) was used to detect the mcr-1-mcr-9 genes, then a further AST, whole genome sequencing (WGS) and bioinformatics analysis were platformed for these DEC isolates which were PCR positive for mcr genes. Results: Seventy in 91 isolates showed different antimicrobial resistance levels to the drugs tested with a resistance rate of 76.92%. The isolates showed the highest antimicrobial resistance rates to ampicillin (69.23%, 63/91) and trimethoprim-sulfamethoxazole (59.34%, 54/91), respectively. The multiple drug-resistant rate was 47.25% (43/91). Two mcr-1 gene and ESBL (extended-spectrum beta-lactamase) positive EAEC (enteroaggregative Escherichia coli) strains were detected. One of them was identified as serotype of O11:H6, which showed a resistance profile to 25 tested drugs referring to 10 classes, and 38 drug resistance genes were predicted by genome analysis. The other one was O16:H48 serotype, which was resistant to 21 tested drugs belonging to 7 classes and carried a new variant of mcr-1 gene (mcr-1.35). Conclusion: An overall high-level antimicrobial resistance was found among foodborne DEC isolates recovered from parts of China in 2020, and so was the MDR (multi-drug resistance) condition. MDR strains carrying multiple resistance genes such as mcr-1 gene were detected, and a new variant of mcr-1 gene was also found. It is necessary to continue with a dynamic monitoring on DEC contamination and an ongoing research into antimicrobial resistance mechanisms.

Construction of folate receptors and mitochondria targeting celastrol-loaded PAMAM nano-drug delivery system and its in vitro anti-inflammatory effect / 药学学报

Pro-inflammatory macrophages play key regulatory role in the occurrence and development of rheumatoid arthritis (RA). In this study, we constructed a celastrol (Cel)-loaded polyamide-amine dendrimer (PAMAM) drug delivery system, which could target folate receptor and mitochondria. It could target inflammatory macrophages and realize chemo-photothermal synergistic therapy. Using PAMAM as the nano-carrier, folate receptor-targeting group folic acid (FA) and mitochondria-targeting group IR808 (also known as the photothermal agent) were conjugated with PAMAM through amide reaction, and then complexed with anti-inflammatory drug Cel to prepare the FA-PAMAM-IR808/Cel nanocomplex. In vitro characterization results showed that the drug loading efficiency of the nanocomplex was 50.90%, particle size was between 130 and 160 nm, average potential was between 1.0 and 3.5 mV, the drug release showed pH sensitivity, temperature reached to 42.5 ℃ after near-infrared (NIR) light irradiation for 10 min. In vitro cellular uptake experiments showed that the nanocomplex had obvious folate receptor-targeting and mitochondria-targeting ability. Following irradiation with NIR light, the cytotoxicity and cellular apoptosis enhanced. The secretion of pro-inflammatory factors tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and nitric oxide (NO) decreased in a concentration-dependent manner. This study provided insights for the development of novel anti-RA nanomedicines.