Noninvasive Diagnostic Technique for Nonalcoholic Fatty Liver Disease Based on Features of Tongue Images / 中国结合医学杂志

OBJECTIVE@#To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease (NAFLD) based on features of tongue images.@*METHODS@#Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, after a series of corrections and data cleaning. The algorithm was trained on images using labels and several anthropometric indexes for inputs, utilizing machine learning technology. Finally, a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD.@*RESULTS@#A total of 720 subjects were enrolled in this study, including 432 patients with NAFLD and 288 healthy volunteers. Of them, 482 were randomly allocated into the training set and 238 into the validation set. The diagnostic model based on logistic regression exhibited excellent performance: in validation set, it achieved an accuracy of 86.98%, sensitivity of 91.43%, and specificity of 80.61%; with an area under the curve (AUC) of 0.93 [95% confidence interval (CI) 0.68-0.98]. The decision tree model achieved an accuracy of 81.09%, sensitivity of 91.43%, and specificity of 66.33%; with an AUC of 0.89 (95% CI 0.66-0.92) in validation set.@*CONCLUSIONS@#The features of tongue images were associated with NAFLD. Both the 2 diagnostic models, which would be convenient, noninvasive, lightweight, rapid, and inexpensive technical references for early screening, can accurately distinguish NAFLD and are worth further study.

Baihe Wuyaotang Ameliorates NAFLD by Enhancing mTOR-mediated Liver Autophagy / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10-3 g·kg-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β1/drosophila mothers against decapentaplegic protein2/3（TGF-β1/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β1 proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

Effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism / 环境与职业医学

Background Long-term exposure to noise during sleep may has adverse effects on metabolic system, and liver lipid metabolism is closely related to circadian clock genes. Objective To investigate the effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism in mice and its related mechanism. Methods Twenty C57BL/6J male mice were randomly divided into two groups: a noise exposure group and a control group with 10 mice in each group. The mice in the noise exposure group were exposed to white noise at 90 dB sound pressure level (SPL) for 30 consecutive days, 8 h a day, from 9:00 to 17:00. The mice in the control group were exposed to background noise ≤40 dB SPL. After noise exposure, the animals were neutralized at 14:00 (ZT6) and 2:00 (ZT18), 5 animals at each time spot, and the liver tissues were collected. Total cholesterol and triglyceride in liver were determined by cholesterol oxidase method and glycerol phosphate oxidase method respectively. The expressions of circadian clock genes (Clock, Bmal1, Rev-erbα, and Rev-erbβ) and lipid metabolism genes (Srebp1c, Hmgcr, Fasn, Lxrα, Acc1, and Chrebp) in liver were detected by quantitative real-time PCR. Results Compared with the control group, the content of total cholesterol in liver in the noise exposure group increased by 48% (P<0.05) and the content of liver triglyceride increased by 61% (P<0.05) at ZT18. The mRNA expression levels of circadian clock genes Clock and Bmal1 in the noise exposure group was significantly increased at ZT18 and decreased at ZT6 (P<0.05). The mRNA expression level of Rev-erbα decreased at both ZT6 and ZT18 (P<0.05). The mRNA expression level of Rev-erbβ had no significant change at ZT6 and ZT18. The mRNA expression levels of liver lipid metabolism related genes Srebp1c, Hmgcr, Chrebp, and Lxrα in the noise exposure group were higher than those in the control group at ZT18 (P<0.05). The mRNA expression levels of Acc1 and Fasn showed no significant change at ZT6, then an upward trend at ZT18, but no significant difference between the two time spots (P>0.05). Conclusion Long-term noise exposure during sleep can cause circadian clock and lipid metabolism disorders in mice. Among them, suppression of key circadian clock genes may be associated with Rev-erbα-mediated upregulation of the nuclear receptors Srebp1c and Chrebp for lipid synthesis and deposition in the liver, resulting in lipid metabolism disorder.

Exploring the mechanism of Xihuang Pill's anti-hyperplasia of mammary glands effect based on UPLC-Q-orbitrap-MS technology / 药学学报

Based on UPLC-Q-orbitrap-MS and biological network analysis tools, the mechanism of Xihuang Pill in improving hyperplasia of mammary glands was systematically analyzed. The rat model of hyperplasia of mammary glands was established by intramuscular injection of estradiol benzoate and progesterone. LC-MS tissue metabolomics was used to explore the key metabolites and metabolic pathways of Xihuang Pill in improving hyperplasia of mammary glands in rat. The network analysis of the key metabolites regulated by Xihuang Pill was carried out by integrating biological network analysis tools, focusing on the key metabolic pathways, and exploring the potential targets of Xihuang Pill to improve hyperplasia of mammary glands. Compared with the control group, there were significant differences in the content of 49 differential metabolites in the tissues of the model group (P < 0.05). Xihuang Pills could significantly call back 17 metabolites such as L-alanine, threonine, indole-3-carboxylic aldehyde, lysine, arginine, alanylleucine, glycyltyrosine, γ-glutamyl leucine, vitamin B3, serine leucine, threonine leucine, isoleucine glutamic acid, γ-glutamyl tyrosine, decanoyl-L-carnitine, uric acid, leucylleucine, S-adenosyl-methionine. Further network analysis and literature research on the key metabolites regulated by Xihuang Pills showed that the AGE-RAGE signaling pathway may be one of the important pathways for Xihuang Pills to improve hyperplasia of mammary glands. STAT3, MAPK1, EGFR, CASP3, CASP8, PRKCA and JUN in the AGE-RAGE signaling pathway may be potential targets for Xihuang Pills to improve hyperplasia of mammary glands. The animal experiment operations involved in this paper follow the provisions of the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine and pass the ethical review of animal experiments (approval number: 2022-705).

Lung transplantation after paraquat poisoning in an adolescent: one case report and literature review / 器官移植

Objective To summarize the effect of the timing of lung transplantation and related treatment measures on clinical prognosis of patients with paraquat poisoning. Methods Clinical data of a patient with paraquat poisoning undergoing bilateral lung transplantation were retrospectively analyzed. Clinical manifestations, auxiliary examination, diagnosis and treatment of this patient were summarized and analyzed. Results A 17-year-old adolescent was admitted to hospital due to nausea, vomiting, cough and systemic fatigue after oral intake of 20-30 mL of 25% paraquat. After symptomatic support treatment, the oxygen saturation was not improved, and pulmonary fibrosis continued to progress. Therefore, sequential bilateral lung transplantation was performed under extracorporeal membrane oxygenation (ECMO). After postoperative rehabilitation and active prevention and treatment for postoperative complications, the patient was discharged at postoperative 50 d. Conclusions The timing of lung transplantation after paraquat poisoning may be selected when the liver and kidney function start to recover. Active and targeted prevention of potential pathogen infection in perioperative period and early rehabilitation training contribute to improving clinical prognosis of lung transplant recipients.

Effect and Mechanism of Total Saponins from Panax Japonicus on White Adipose Tissue Browning/Brown Adipose Tissue Activation in High-fat Diet-induced Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of total saponins from Panax japonicus （TSPJ） on white adipose tissue （WAT） browning/brown adipose tissue （BAT） activation in C57BL6/J male mice fed on a high-fat diet （HFD）. MethodThirty-two C57BL6/J male mice （8-week-old） were randomly divided into a normal group， a model group， a low-dose TSPJ group， and a high-dose TSPJ group. The mice in the low-dose and high-dose TSPJ groups were given TSPJ for four months by gavage at 25， 75 mg·kg-1·d-1， respectively， and those in the other groups were given 0.5% sodium carboxymethyl cellulose （CMC-Na） accordingly. After four months of feeding， all mice were placed at 4 ℃ for acute cold exposure， and the core body temperature was monitored. Subsequently， all mice were sacrificed， and BAT and inguinal WAT （iWAT） were separated rapidly to detect the corresponding indexes. Hematoxylin-eosin （HE） staining was used to observe the morphological changes in each group. The effect of TSPJ on the mRNA expression of uncoupling protein 1 （UCP1）， fatty acid-binding protein 4 （FABP4）， cytochrome C （CytC）， PR domain-containing protein 16 （PRDM16）， elongation of very long chain fatty acids protein 3 （ELOVL3）， peroxisome proliferator-activated receptor γ （PPARγ）， and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） in iWAT and BAT was detected by Real-time polymerase chain reaction （Real-time PCR）. Western blot was also used to detect the protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in BAT and iWAT of each group. The effect of TSPJ on UCP1 expression in BAT and iWAT was detected by immunohistochemistry. Result① Compared with the model group， TSPJ could decrease the body weight and proportions of iWAT and BAT in the HFD-induced mice （P<0.05， P<0.01）. ② The body temperature of mice in the model group decreased compared with that in the normal group in the acute cold exposure tolerance test （P<0.05）. The body temperature in the high-dose TSPJ group increased compared with that in the model group （P<0.01）. ③ Compared with the normal group， the model group showed increased adipocyte diameter in iWAT and BAT and decreased number of adipocytes per unit area. Compared with the model group， the TSPJ groups showed significantly reduced cell diameter and increased number of cells per unit area， especially in the high-dose TSPJ group. ④ Compared with the normal group， the model group showed decreased mRNA expression of FABP4， UCP1， CytC， PRDM16， ELOVL3， PGC-1α， and PPARγ in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the mRNA expression was significantly up-regulated （P<0.05， P<0.01）. ⑤ Compared with the normal group， the model group showed decreased protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the protein expression increased significantly （P<0.05， P<0.01）. ConclusionTSPJ could induce the browning of iWAT/BAT activation and enhance adaptive thermogenesis in obese mice induced by HFD. The underlying mechanism may be attributed to the activation of the PPARγ/PGC-1α signaling pathway.

Security analysis of sports competition under the influence of covid-19 / Análise de segurança da competição esportiva sob a influência da covid-19 / Análisis de seguridad de la competición deportiva bajo la influencia del covid-19

ABSTRACT Introduction The continuous growth of COVID-19 has harmed sports competitions. Although the existing method of non-opening to spectators is very effective for preventing and controlling COVID-19, it will also seriously blow the sports economy's development. Objective Explore the safety of sports competition under the influence of COVID-19 to realize sports practice in a safe and regulated condition. Methods Firstly, the current public's willingness to participate in the competition was analyzed by questionnaire survey. Then, using the literature search method, this paper discusses the safety needs of sports competitions under the normalization of the prevention and control of COVID-19 in the research area at the present stage. Results By completely controlling the crowd shift rule and skillfully controlling the crowd pace, the transmission risk in the competition process can be effectively reduced. Conclusion The relevant departments and stadium managers should fully analyze the current epidemic prevention and control needs and strengthen spectator safety management in the study area in combination with regional characteristics and the actual spectator situation. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução O crescimento contínuo da COVID-19 tem tido um impacto negativo sobre as competições esportivas. Embora o método existente de não-abertura aos espectadores seja muito eficaz para a prevenção e controle da COVID-19, ele também trará um sério golpe ao desenvolvimento da economia esportiva. Objetivo Explorar a segurança da competição esportiva sob a influência da COVID-19, de forma a realizar a prática esportiva em uma condição segura e regulamentada. Métodos Primeiramente, a disposição do público atual para participar da competição foi analisada por meio de pesquisa por questionário. Em seguida, utilizando o método de pesquisa bibliográfica, este trabalho discute as necessidades de segurança das competições esportivas sob a normalização da prevenção e controle da COVID-19 na área de pesquisa na presente fase. Resultados Controlando completamente a regra do deslocamento da multidão e controlando habilmente o ritmo da multidão, o risco de transmissão no processo de competição pode ser efetivamente reduzido. Conclusão Os departamentos e gerentes de estádios pertinentes devem analisar plenamente as necessidades atuais de prevenção e controle de epidemias e fortalecer a gestão da segurança dos espectadores na área de estudo em combinação com as características regionais e a situação real dos espectadores. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El continuo crecimiento del COVID-19 ha tenido un impacto negativo en las competiciones deportivas. Aunque el método actual de no abrir para los espectadores es muy eficaz para la prevención y el control del COVID-19, también supondrá un duro golpe para el desarrollo de la economía deportiva. Objetivo Explorar la seguridad de la competición deportiva bajo la influencia del COVID-19, para llevar a cabo la práctica deportiva en condiciones seguras y reguladas. Métodos En primer lugar, se analizó la disposición del público actual a participar en el concurso mediante una encuesta por cuestionario. A continuación, utilizando el método de búsqueda bibliográfica, este trabajo analiza las necesidades de seguridad de las competiciones deportivas en el marco de la normalización de la prevención y el control del COVID-19 en el ámbito de la investigación en la etapa actual. Resultados Si se controla completamente la regla de desplazamiento de la multitud y se controla hábilmente el ritmo de la multitud, se puede reducir eficazmente el riesgo de transmisión en el proceso de competición. Conclusión Los departamentos competentes y los gestores de los estadios deben analizar a fondo las necesidades actuales de prevención y control de epidemias y reforzar la gestión de la seguridad de los espectadores en la zona de estudio en combinación con las características regionales y la situación real de los espectadores. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Cytotoxicity of 4 Wild Mushrooms in a Case of Yunnan Sudden Unexplained Death / 法医学杂志

OBJECTIVES@#To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD.@*METHODS@#Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope.@*RESULTS@#Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts.@*CONCLUSIONS@#The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

Correlation between spinous process deviation and lumbar disc herniation in young patients / 中国骨伤

OBJECTIVE@#To explore the relationship between spinous process deviation and lumbar disc herniation in young patients.@*METHODS@#From March 2015 to January 2022, 30 treated young (under the age of 30) patients with lumbar disc herniation were included as the young group. In addition 30 middle-aged patients (quinquagenarian group) with lumbar disc herniation and 30 patients with non-degenerative spinal diseases (young non-degenerative group) were selected as control groups. The angle of the spinous process deviation was measured on CT and statistically analyzed by various groups. All the data were measured twice and the average value was taken and recorded.@*RESULTS@#The average angle of spinous process deviation in the degenerative lumbar vertebra of young patients were (3.89±3.77) degrees, similar to the (3.72±2.98) degrees of quinquagenarian patients(P=0.851). The average angle of s spinous process deviation young non-degenerative group were (2.20±2.28) degrees, significantly less than young group(P=0.040). The spinous process deviation angle of the superior vertebral of the degenerative lumbar in the young group was (4.10±3.44) degrees, which similar to the (3.47±2.87) degrees in the quinquagenarian group (P=0.447). A total of 19 young patients had the opposite deviation direction of the spinous process of the degenerative lumbar vertebra and upper vertebra, while only 7 quinquagenarian patients had this condition(P=0.02). The type of lumbar disc herniation in young patients had no significant relationship with the direction of spinous process deflection of the degenerative or upper lumbar vertebra (P>0.05).@*CONCLUSION@#Spinous process deviation is a risk factor of young lumbar disc herniation patients. If the deviation directions of adjacent lumbar spinous processes are opposite, it will increase the incidence of lumbar disc herniation in young patients. There was no significant correlation between the type of disc herniation and the deviation direction of the spinous process of the degenerative or upper lumbar vertebra. People with such anatomical variation can strengthen the stability of spine and prevent lumbar disc herniation through reasonable exercise.

Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope / 中国中药杂志

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.

Genetic and Phenotypic Variation of Campylobacter jejuni NCTC11168 Caused by flhA Mutation during Laboratory Passage / 生物医学与环境科学（英文）

OBJECTIVE@#Campylobacter jejuni NCTC11168 is commonly used as a standard strain for flagellar biosynthesis research. In this report, two distinguished phenotypic isolates (CJ1Z, flhA mutant strain, lawn; CJ2S, flhA complemented strain, normal colony) appeared during laboratory passages for NCTC11168.@*METHODS@#Phenotypic assessments, including motility plates, transmission electron microscopy, biofilm formation assay, autoagglutination assay, and genome re-sequencing for these two isolates (CJ1Z, flhA mutant strain; CJ2S, flhA complemented strain) were carried out in this study.@*RESULTS@#Transmission electron microscopy revealed that the flagellum was lost in CJ1Z. Phenotypic assessments and genome sequencing of the two isolates were performed in this study. The capacity for biofilm formation, colony auto-agglutination, and isolate motility was reduced in the mutant CJ1Z. Comparative genomic analysis indicated a unique native nucleotide insertion in flhA (nt, 2154) that caused the I719Y and I720Y mutations and early truncation in flhA.@*CONCLUSION@#FlhA has been found to influence the expression of flagella in C. jejuni. To the best of our knowledge, this is the first study to describe the function of the C-terminal of this protein.

Research progress of exosome drug loading system / 中国药房

Exosome is a kind of vesicle secreted by a variety of cells with lipid bilayer membrane structure， which has good biocompatibility， high targeting and high stability， and is a natural nanoscale drug carrier with great development potential in drug delivery system. In this paper， exosomes and their properties， exosome drug delivery pathways and methods， the design strategy of engineered exosome drug delivery systems for targeted disease therapy， and the application of exosome drug delivery systems in the treatment of a variety of diseases were reviewed. Exosome drug delivery pathways could be divided into two categories： exogenous and endogenous. Common exosome drug delivery methods included electroporation， co-incubation， and ultrasound. Engineered exosome drug delivery system can further improve drug loading and enhance drug targeting. The main way of engineering is to modify exosome surface through genetic engineering technology， physical modification， chemical modification， etc. Exosome drug delivery system provides a new idea for targeted therapy of arthritis， tumor， brain and other diseases.

Study on quality control method of Qiguiling mixture / 中国药房

OBJECTIVE To establish the fingerprint of Qiguiling mixture and the method for the content determination of 4 kinds of active components such as calycosin-7-glucoside， so as to control the quality of Qiguiling mixture. METHODS The fingerprints of 12 batches of Qiguiling mixture were established by HPLC. SPSS 25.0 software was used for cluster analysis and principal component analysis， and SIMCA 14.1 software was used for orthogonal partial least squares-discriminant analysis. The variable importance in projection （VIP） value greater than 1.0 was used as the index to screen the differential components. The contents of calycosin-7-glucoside， glycyrrhizin and glycyrrhizic acid were calculated by the quantitative analysis of multi- components by single marker （QAMS） with hesperidin as the internal reference， and the results were compared with external standard method. RESULTS In the fingerprints of 12 batches of samples， 17 common peaks were identified， and the similarities were more than 0.940. A total of 4 common peaks were identified， which were calycosin-7-glucoside （peak 6）， glycyrrhizin （peak 8）， hesperidin （peak 12）， and glycyrrhizic acid （peak 17）. The 12 batches of samples could be clustered into two categories， S4， S7-S9 and S11-S12 were clustered into one category， and the other batches of samples were clustered into one category. The cumulative variance contribution rate of the six principal components was 85.840%， and VIP values of peaks 15， 14， 4， 8 （glycyrrhizin） and 9 were all greater than 1.0. The relative error between the results of QAMS and external standard method was less than 5% （n＝3） for the contents of calycosin-7-glucoside， glycyrrhizin and glycyrrhizic acid. CONCLUSIONS Established HPLC fingerprint and content determination method in this study can be used for quality control of Qigiling mixture. Five components such as glycyrrhizin are the differential components.

Characteristics and influencing factors of cognitive impairment in patients with multiple sclerosis / 公共卫生与预防医学

Objective To observe the characteristics of cognitive impairment in patients with multiple sclerosis (MS) and analyze its influencing factors. Methods A total of 105 patients with MS admitted to the West China Hospital from April 2019 to April 2022 were selected as the MS group, and 30 healthy individuals who received physical examination during the same period were selected as the control group. Both groups were examined with brain magnetic resonance imaging (MRI). The Wechsler Adult Intelligence Scale (WAIS) and Wisconsin Card Sorting Test (WSCT) system were used to evaluate the patients' overall cognitive function. Patients in the MS group were additionally evaluated with the Expanded Disability Status Scale (EDSS). Results On the WAIS scale, the verbal IQ, operational IQ and total IQ of the MS group were lower than those of the control group (P<0.05). The scores for the total number of tests, false responses, persistent errors, and non-persistent errors in the WSCT of the MS group were higher than those in the control group, while the scores for classification, correct responses, and percentage of correct responses were lower than those in the control group (P<0.05). The operation IQ (r= -0.695) and SDS score (r= -0.420) were negatively correlated with EDSS score in the MS group (P<0.05). Conclusion Patients with MS have cognitive impairment, which manifests as the reduction of summary abstraction, comprehension and expression, thinking and observation, structural synthesis of memory ability, abstract spatial skills and executive function. The more severe the physical dysfunction, the lower the operational IQ score.

Anti-inflammatory Effect and Mechanism of Duhuo Jishengtang on Rheumatoid Arthritis Rats Based on TLR2/p38 MAPK/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the anti-inflammatory effect of Duhuo Jishengtang （DHJST） on collagen-induced arthritis （CIA） model rats and its effect on the Toll-like receptor 2 （TLR2）/p38 mitogen-activated protein kinase （MAPK）/nuclear factor-κB （NF-κB） signaling pathway. MethodForty-eight male SD rats were randomly divided into the following six groups （n=8）： normal group， model group， methotrexate （MTX） group， low-dose DHJST （DHJST-L） group， medium-dose DHJST （DHJST-M） group， and high-dose DHJST （DHJST-H） group. The CIA model was established by injecting bovine type Ⅱ collagen into the rat tail root with the collagen antibody induction method. After model induction， rats were treated with drugs by gavage. The rats in the MTX group received MTX at 2.0 mg·kg-1， three times a week， and those in the DHJST groups received DHJST at 3.8， 7.6， 15.2 g·kg-1·d-1 for 28 days. The rats in the normal group and the model group were given the same dose of normal saline. The weight of the rats was recorded， and the paw swelling degree was observed. The arthritis index and immune organ index were measured， and the changes in the microcirculation indexes of the rats were detected with a microcirculation detector. Hematoxylin-eosin （HE） staining was used to detect the pathological morphologic changes in rat synovial tissues and the apoptosis rate of synovial cells was detected by flow cytometry to determine the therapeutic effect of DHJST on rheumatoid arthritis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the changes in serum levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-17A， and interferon-γ （IFN-γ）. The protein expression of TLR2， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， p38 MAPK， and p-p38 MAPK was detected by Western blot. ResultCompared with the normal group， the model group showed reduced body weight （P<0.01）， increased paw swelling degree， arthritis index， and immune organ index （P<0.01）， increased comprehensive microvascular score and vascular resistance （P<0.01）， significant hyperplasia of synovial tissues and massive infiltration of inflammatory cells as revealed by pathological sections， and up-regulated expression levels of TNF-α， IL-1β， IL-17A， and IFN-γ in serum， and TLR2， p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in synovial tissues （P<0.01）. Compared with the model group， the DHJST groups showed increased body weight of rats （P<0.01）， decreased paw swelling degree， arthritis index， and immune organ index （P<0.05， P<0.01）， reduced comprehensive microvascular score and vascular resistance （P<0.05， P<0.01）， improved synovial histopathological injury， increased apoptosis rate of synovial cells （P<0.01）， and down-regulated levels of TNF-α， IL-1β， IL-17A， and IFN-γ in serum （P<0.05， P<0.01） and TLR2， p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in synovial tissues （P<0.05， P<0.01）. ConclusionDHJST may alleviate the inflammatory reaction in CIA rats by regulating the TLR2/p38 MAPK/NF-κB signaling pathway， thus exerting its anti-rheumatoid arthritis effect.

A novel and low-toxic peptide DR3penA alleviates pulmonary fibrosis by regulating the MAPK/miR-23b-5p/AQP5 signaling axis

Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH2) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH2) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.

Synergistic activation of AMPK by AdipoR1/2 agonist and inhibitor of EDPs-EBP interaction recover NAFLD through enhancing mitochondrial function in mice

Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), is a common hepatic manifestation of metabolic syndrome. However, there are no effective therapy to treat this devastating disease. Accumulating evidence suggests that the generation of elastin-derived peptides (EDPs) and the inhibition of adiponectin receptors (AdipoR)1/2 plays essential roles in hepatic lipid metabolism and liver fibrosis. We recently reported that the AdipoR1/2 dual agonist JT003 significantly degraded the extracellular matrix (ECM) and ameliorated liver fibrosis. However, the degradation of the ECM lead to the generation of EDPs, which could further alter liver homeostasis negatively. Thus, in this study, we successfully combined AdipoR1/2 agonist JT003 with V14, which acted as an inhibitor of EDPs-EBP interaction to overcome the defect of ECM degradation. We found that combination of JT003 and V14 possessed excellent synergistic benefits on ameliorating NASH and liver fibrosis than either alone since they compensate the shortage of each other. These effects are induced by the enhancement of the mitochondrial antioxidant capacity, mitophagy, and mitochondrial biogenesis via AMPK pathway. Furthermore, specific suppression of AMPK could block the effects of the combination of JT003 and V14 on reduced oxidative stress, increased mitophagy and mitochondrial biogenesis. These positive results suggested that this administration of combination of AdipoR1/2 dual agonist and inhibitor of EDPs-EBP interaction can be recommended alternatively for an effective and promising therapeutic strategy for the treatment of NAFLD and NASH related fibrosis.

Association of Glial Activation and α-Synuclein Pathology in Parkinson's Disease / 神经科学通报·英文版

The accumulation of pathological α-synuclein (α-syn) in the central nervous system and the progressive loss of dopaminergic neurons in the substantia nigra pars compacta are the neuropathological features of Parkinson's disease (PD). Recently, the findings of prion-like transmission of α-syn pathology have expanded our understanding of the region-specific distribution of α-syn in PD patients. Accumulating evidence suggests that α-syn aggregates are released from neurons and endocytosed by glial cells, which contributes to the clearance of α-syn. However, the activation of glial cells by α-syn species produces pro-inflammatory factors that decrease the uptake of α-syn aggregates by glial cells and promote the transmission of α-syn between neurons, which promotes the spread of α-syn pathology. In this article, we provide an overview of current knowledge on the role of glia and α-syn pathology in PD pathogenesis, highlighting the relationships between glial responses and the spread of α-syn pathology.

Research progress in pH-responsive antibacterial nanomaterials for inhibiting oral plaque biofilms / 中华口腔医学杂志

pH-responsive antibacterial nanomaterials are a new type of nanomaterials that can selectively undergo structural changes and trigger drug release according to significant pH differences produced by the body under physiological and pathological conditions. The formation of acidic microenvironment in plaque is the key to the pathogenicity of oral plaque biofilm, which also creates conditions for the oral application of pH-responsive antibacterial nanomaterials. pH-responsive antibacterial nanomaterials can respond to changes in pH of plaque microenvironment and accurately control the release of antibacterial drugs, providing a new direction for improving drug efficacy and targeted antibacterial. The present article reviews the classification, mechanism and application of pH-responsive antibacterial nanomaterials in oral plaque inhibition.

The role of Keap1/Nrf2/HO-1 signal pathway in liver injury induced by rare earth neodymium oxide in mice / 中华劳动卫生职业病杂志

Objective: To investigate the role of Keap1/Nrf2/HO-1 signaling pathway in liver injury induced by neodymium oxide (Nd(2)O(3)) in mice. Methods: In March 2021, forty-eight SPF grade healthy male C57BL/6J mice were randomly divided into control group (0.9% NaCl), low dose group (62.5 mg/ml Nd(2)O(3)), medium dose group (125.0 mg/ml Nd(2)O(3)), and high dose group (250.0 mg/ml Nd(2)O(3)), each group consisted of 12 animals. The infected groups were treated with Nd(2)O(3) suspension by non-exposed tracheal drip and were killed 35 days after dust exposure. The liver weight of each group was weighed and the organ coefficient was calculated. The content of Nd(3+) in liver tissue was detected by inductively coupled plasma mass spectrometry (ICP-MS). HE staining and immunofluorescence was used to observe the changes of inflammation and nuclear entry. The mRNA expression levels of Keap1, Nrf2 and HO-1 in mice liver tissue were detected by qRT-PCR. Western blotting was used to detect the protein expression levels of Keap1 and HO-1. The contents of catalase (CAT), glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) were detected by colorimetric method. The contents of interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were determined by ELISA. The data was expressed in Mean±SD. Two-independent sample t-test was used for inter-group comparison, and one-way analysis of variance was used for multi-group comparison. Results: Compared with the control group, the liver organ coefficient of mice in medium and high dose groups were increased, and the Nd(3+) accumulation in liver of mice in all dose groups were significantly increased (P<0.05). Pathology showed that the structure of liver lobules in the high dose group was slightly disordered, the liver cells showed balloon-like lesions, the arrangement of liver cell cords was disordered, and the inflammatory exudation was obvious. Compared with the control group, the levels of IL-1β and IL-6 in liver tissue of mice in all dose groups were increased, and the levels of TNF-α in liver tissue of mice in high dose group were increased (P<0.05). Compared with the control group, the mRNA and protein expression levels of Keap1 in high dose group were significantly decreased, while the mRNA expression level of Nrf2, the mRNA and protein expression levels of HO-1 were significantly increased (P<0.05), and Nrf2 was successfully activated into the nucleus. Compared with the control group, the activities of CAT, GSH-Px and T-SOD in high dose group were significantly decreased (P<0.05) . Conclusion: A large amount of Nd(2)O(3) accumulates in the liver of male mice, which may lead to oxidative stress and inflammatory response through activation of Keap1/Nrf2/HO-1 signal pathway. It is suggested that Keap1/Nrf2/HO-1 signal pathway may be one of the mechanisms of Nd(2)O(3) expose-induced liver injury in mice.