Antiviral Effect of Extracellular Matrix Protein ABI3BP on Vesicular Stomatitis Virus and Its Mechanism: A Preliminary Study In Vitro.

Objective To explore the influence of extracellular matrix protein ABI-interactor 3-binding protein (ABI3BP) on vesicular stomatitis virus (VSV) genome replication and innate immune signaling pathway.Methods The small interfering RNA (siRNA) was transfected to knock down ABI3BP gene in human skin fibroblast BJ-5ta cells. VSV-green fluorescent protein (VSV-GFP)-infected cell model was established. The morphological changes and F-actin stress fiber formation were detected on ABI3BP knockdown cells by phalloidin immunofluorescence staining. The mRNA level of virus replication was detected by RT-qPCR in BJ-5ta cells after VSV-GFP infection; western blotting was performed to detect the changes in interferon regulatory factor 3 (IRF3) and TANK-binding kinase 1 (TBK1) phosphorylation levels.Results The VSV-GFP-infected BJ-5ta cell model was successfully established. Efficient knockdown of ABI3BP in BJ-5ta cells was achieved. Phalloidin immunofluorescence staining revealed structural rearrangement of intracellular F-actin after ABI3BP gene knockdown. Compared with the control group, the gene copy number of VSV-GFP in ABI3BP knockdown cells increased by 2.2 - 3.5 times (P<0.01) and 2.2 - 4.0 times (P<0.01) respectively when infected with VSV of multiplicity of infection 0.1 and 1. The expression of viral protein significantly increased in ABI3BP knockdown cells after virus infection. The activation of type-I interferon pathway, as determined by phosphorylated IRF3 and phosphorylated TBK1, was significantly decreased in ABI3BP knockdown cells after VSV-GFP infection.Conclusions Extracellular matrix protein ABI3BP plays an important role in maintaining the formation and rearrangement of actin structure. ABI3BP gene deletion promotes RNA virus replication, and ABI3BP is an important molecule that maintains the integrity of type I interferon pathway.

Manipulation of Conducting Polymer Hydrogels with Different Shapes and Related Multifunctionality.

Maneuver of conducting polymers (CPs) into lightweight hydrogels can improve their functional performances in energy devices, chemical sensing, pollutant removal, drug delivery, etc. Current approaches for the manipulation of CP hydrogels are limited, and they are mostly accompanied by harsh conditions, tedious processing, compositing with other constituents, or using unusual chemicals. Herein, a two-step route is introduced for the controllable fabrication of CP hydrogels in ambient conditions, where gelation of the shape-anisotropic nano-oxidants followed by in-situ oxidative polymerization leads to the formation of polyaniline (PANI) and polypyrrole hydrogels. The method is readily coupled with different approaches for materials processing of PANI hydrogels into varied shapes, including spherical beads, continuous wires, patterned films, and free-standing objects. In comparison with their bulky counterparts, lightweight PANI items exhibit improved properties when those with specific shapes are used as electrodes for supercapacitors, gas sensors, or dye adsorbents. The current study therefore provides a general and controllable approach for the implementation of CP into hydrogels of varied external shapes, which can pave the way for the integration of lightweight CP structures with emerging functional devices.

Overview of Research on Intervention Methods in the Mechanism of Acupuncture Treatment of Cocaine Addiction / 世界科学技术-中医药现代化

Cocaine,as a widely abused and highly addictive drug,has a serious impact on the physical and mental health of individuals and carries a certain degree of social harm and economic burden.Acupuncture can assist in the treatment of cocaine addiction with fewer side effects.However,a well-defined mode of stimulation is an important factor in elucidating the various mechanisms by which acupuncture treats disease.This paper summarizes the problems in the mechanism of cocaine addiction,such as different parameters of stimulation,unstable depth of acupuncture,different acupoint selection,and different lengths of acupuncture time.To standardize the intervention measures of acupuncture experiments,it is suggested that in future research,the stimulation method should explore the best parameters,the selection of acupoints should be based on clinical practice,the timing of acupuncture should be objective,and the treatment course should consider the effects of acupuncture.

Effects of Rosa roxburghii Radix on ulcerative colitis in rats based on pyroptosis and neutrophil extracellular traps / 中成药

AIM To explore the effects of Rosa roxburghii Radix on ulcerative colitis(UC)in rats based on pyroptosis and neutrophil extracellular traps(NETs).METHODS Rats were randomly divided into the normal group and the model group.The successfully established UC rat models by trinitrobenzene sulfonic acid(TNBS)/ethanol enema were then randomly divided into the model group,the sulfasalazine group(0.3 g/kg)and the low,medium and high dose R.roxburghii Radix groups(2,4,8 g/kg),followed by dosing of corresponding drugs by gavage.21 days later,the rats had their disease activity index(DAI)score calculated;their pathological changes of colon tissue observed by HE staining;their levels of serum interleukin(IL)-18,IL-1β and myeloperoxidase(MPO)detected by ELISA;and their protein expressions of NE,MPO,NLRP3,caspase-1 and GSDMD in colon tissue detected by Western blot and immunohistochemistry.RESULTS Compared with the normal group,the model group displayed increased DAI score(P＜0.01),increased serum levels of IL-1β,IL-18 and MPO(P＜0.01),and increased protein expressions of NE,MPO,caspase-1,NLRP3 and GSDMD in colon tissue(P＜0.01).Compared with the model group,the groups intervened with sulfasalazine,or medium,or high dose R.roxburghii Radix demonstrated with decreased DAI scores(P＜0.05,P＜0.01),decreased serum levels of IL-1β,IL-18 and MPO(P＜0.01),and decreased protein expressions of NE,MPO,caspase-1,NLRP3 and GSDMD in colon tissue(P＜0.05,P＜0.01).CONCLUSION R.roxburghii Radix may alleviate the inflammatory reaction in a rat model of UC and improve its pathological injury of colon via regulating pyroptosis and NETs.

Magnifying endoscopy combined with narrow-band imaging,acetate-indigo rouge staining combined with multi-slice spiral CT in the diagnosis of early gastric cancer and precancerous lesions and clinical significance / 中国内镜杂志

Objective To analyze the diagnostic efficacy and clinical significance of magnifying endoscopy combined with narrow-band imaging(ME-NBI),acetate-indigo rouge staining and multi-slice spiral CT for early gastric cancer and precancerous lesions.Methods 202 patients with suspected early gastric cancer and precancerous lesions from February 2019 to March 2022 were regarded as the subjects of this study,all the patients underwent ME-NBI,acetate-indigo rouge staining,and multi-slice spiral CT examination;The diagnostic value of different examination methods for early gastric cancer and precancerous lesions was analyzed using the receiver operator characteristic curve(ROC curve),using the pathological results of gastric cancer as the gold standard,the diagnostic value of ME-NBI,acetate-indigo rouge staining combined with multi-slice spiral CT and their combination in early gastric cancer and precancerous lesions was analyzed using a four grid table.Results The image quality of ME-NBI and acetate-indigo rouge staining combined examinations was significantly higher than that of their respective independent examinations(P<0.05).There was significant difference in the degree of differentiation in the clinical features of patients with early gastric cancer and precancerous lesions(P<0.05).The area under the curve(AUC)of ME-NBI for the diagnosis of early gastric cancer and precancerous lesions was 0.853,the accuracy was 85.64%,the sensitivity was 88.37%,and the specificity was 83.62%.The AUC of acetate-indigo rouge staining for the diagnosis of early gastric cancer and precancerous lesions was 0.814,the accuracy was 81.68%,the sensitivity was 83.72%,and the specificity was 80.17%.The AUC of multi-slice spiral CT for the diagnosis of early gastric cancer and precancerous lesions was 0.804,with an accuracy of 80.69%,a sensitivity of 82.56%,and a specificity of 79.31%.And the AUC of the three methods combined to diagnose early gastric cancer and precancerous lesions was 0.893,with an accuracy of 89.60%,a sensitivity of 93.02%,and a specificity of 87.07%.Conclusion ME-NBI,acetate-indigo rouge staining combined with multi-slice spiral CT has high diagnostic efficacy in early gastric cancer and precancerous lesions,and can be used in clinical practice.

Polarization-insensitive phase-modulated metasurface using single thermally stimulated vanadium dioxide chip.

Considering that typically more than two pin diodes or other tunable elements are required in the unit cell of polarization-insensitive reconfigurable metasurfaces (RMs), this paper proposes a new approach to design a polarization-insensitive RM unit using only one VO2 chip. A polarization-insensitive phase-modulated metasurface (PMM) using single VO2 chip is presented. The surface layer is composed of an outer ring and an inner cross, with a VO2 chip loaded at the connection of the cross. As the VO2 chip can be connected with the metal patch on all sides, only one VO2 chip is used in this polarization-insensitive design. By thermally controlling VO2 chips switch between low-resistance and high-resistance states, the PMM achieves a 1-bit phase shift within 180° ± 37° from 7.85 to 15 GHz. A prototype is fabricated and measured, and the measured results have verified the correction of the design and analysis of the designed PMM.

Regulation mechanism of human insulin fibrillation by L-lysine carbon dots: low concentration accelerates but high concentration inhibits the fibrillation process.

The fibrillation process of human insulin (HI) is closely related to the therapy for type II diabetes (T2D). Due to changes in the spatial structure of HI, the fibrillation process of HI takes place in the body, which leads to a significant decrease in normal insulin levels. L-Lysine CDs with a size of around 5 nm were synthesized and used to adjust and control the fibrillation process of HI. ThT fluorescence analysis and transmission electron microscopy (TEM) characterization of the CDs showed the role of HI fibrillation from the perspective of the kinetics of HI fibrillation and regulation. Isothermal titration calorimetry (ITC) was used to explore the regulatory mechanism of CDs at all stages of HI fibrillation from the perspective of thermodynamics. Contrary to common sense, when the concentration of CDs is less than 1/50 of the HI, CDs will promote the growth of fibres, while a high concentration of CDs will inhibit the growth of fibres. The experimental results of ITC clearly prove that different concentrations of CDs will correspond to different pathways of the combination between CDs and HI. CDs have a strong ability to combine with HI during the lag time, and the degree of combination has become the main factor influencing the fibrillation process.

Inhibition mechanism of human insulin fibrillation by Bodipy carbon polymer dots and photothermal defibrillation effect of Bodipy carbon polymer dots modified by ThT.

Fibrillation process of human insulin (HI) is closely related to type 2 diabetes (T2D). In the present work, Carbon Polymer Dots (CPDs) was synthesized by Bodipy to control the process of insulin fibrillation. The inhibition process of insulin fibrillation with the existence of CPDs was completed investigated. The hydrophobic interaction of CPDs and insulin was used to inhibit the change of insulin's secondary structure in the lag phase and growth period. ThT fluorescence analysis and transmission electron microscopy (TEM) characterization of the CPDs were used to explore the kinetics of insulin fibrillation and regulation process by CPDs. Isothermal titration calorimetry (ITC) was applied to explore the regulatory mechanism by CPDs at all stages of the insulin fibrillation process. ThT was used to complete the chemical modification of CPDs by Friedel-Crafts alkylation, which made the CPDs maintain the characteristics of photothermal effect and also obtain the ability to bind specifically to the fibers. Finally, the process of defibrillation of human insulin fibers under the Near-infrared light's irradiation was realized. In this work, we clarified the mechanism of the regulation process by Bodipy CPDs and made CPDs able to defibrillate the insulin fibers by chemical modification.

Flexible and Robust Triboelectric Nanogenerators with Chemically Prepared Metal Electrodes and a Plastic Contact Interface Based on Low-Cost Pressure-Sensitive Adhesive.

Triboelectric nanogenerators (TENGs) are devices that can harvest energy from mechanical motions; such devices can be used to power wearable sensors and various low-power electronics. To increase the lifetime of the device, scientists mainly use the method of making TENG in a hard skeleton to simplify the complex possible relative movements between two triboelectric parts. However, the hard skeletons cannot be embedded in soft and lightweight clothing. To make matters worse, the materials used in the garments must be able to withstand high mechanical forces when worn, such as the pressure of more than 100 KPa exerted by body pressure or everyday knocks. Notably, the TENGs are usually made of fragile materials, such as vacuum-evaporated metal electrodes and nano-sized coatings, on the contact interface; these electrodes and coatings often chip or wear off under the action of external loads. In this work, we succeeded in creating a thin, light-weight, but extremely robust garment-integrated triboelectric nanogenerator (G-TENG) that can be embedded in clothing and pass the water wash test. First, we chemically deposited a durable electrode with flexible properties for G-TENG using a novel technique called polymer-assisted metal deposition (PAMD). The as-formed metal electrodes are firmly bonded to the plastic substrate by a sub-10 nm adhesive polymer brush and can withstand a pressure of 22.5 MPa and a tear force of 0.7 MPa. We then removed the traditionally used fragile nanoparticle materials and the non-durable poly-dimethylsiloxane (PDMS) layer at the triboelectric interface, and then used a cost-effective, durable and slightly flowable pressure-sensitive adhesive to form a plastic contact interface. Such a soft plastic interface can ensure full contact of the triboelectric materials, which is excellent in complex environments and ultimately improves the power generation efficiency of the devices. The as-formed low-cost energy harvesting device could become an industry standard for future smart clothing.

Clinical characteristics and genetic analysis of a case with adult neuronal ceroid lipofuscinosis type 7 due to variant of MFSD8 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic variants in a patient with adult ceroid lipofuscinosis neuronal type 7 (ACLN7).@*METHODS@#A female patient diagnosed with ACLN7 in Henan Provincial People's Hospital in June 2021 was selected as the study subject. Clinical data, auxiliary examination and result of genetic testing were retrospectively analyzed.@*RESULTS@#The patient, a 39-year-old female, has mainly presented progressive visual loss, epilepsy, cerebellar ataxia and mild cognitive decline. Neuroimaging analysis has revealed generalized brain atrophy, prominently cerebellum. Fundus photography has revealed retinitis pigmentosa. Ultrastructural skin examination has revealed granular lipofuscin deposits in the periglandular interstitial cells. Whole exome sequencing revealed that she has harbored compound heterozygous variants of the MSFD8 gene, namely c.1444C>T (p.R482*) and c.104G>A (p.R35Q). Among these, c.1444C>T (p.R482*) was a well established pathogenic variant, while c.104G>A (p.R35Q) was a missense variant unreported previously. Sanger sequencing confirmed that the daughter, son and elder brother of the proband have respectively carried heterozygous c.1444C>T (p.R482*), c.104G>A (p.R35Q), and c.104G>A (p.R35Q) variants of the same gene. The family has therefore fit with the autosomal recessive inheritance pattern of the CLN7.@*CONCLUSION@#Compared with previously reported cases, this patient has the latest onset of the disease with a non-lethal phenotype. Her clinical features have involved multiple systems. Cerebellar atrophy and fundus photography may be indicative of the diagnosis. The c.1444C>T (p.R482*) and c.104G>A (p.R35Q) compound heterozygous variants of the MFSD8 gene probably underlay the pathogenesis in this patient.

Differences in clinicopathological features, gene mutations, and prognosis between primary gastric and intestinal gastrointestinal stromal tumors in 1061 patients / 中华胃肠外科杂志

Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm2), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.

Genetic analysis of neonates with abnormal isovaleryl carnitine metabolism / 中华实用儿科临床杂志

Objective:To explore the genetic causes of abnormal isovaleryl carnitine (C5) metabolism in newborns.Methods:Retrospective study.The screening and clinical follow-up data of 34 neonates with elevated C5 levels shown by the tandem mass spectrometry test in Children′s Hospital, Zhejiang University School of Medicine from January 2018 to December 2021 were collected.Afterwards, their ethylenediaminetetraacetic acid (EDTA) anticoagulant venous blood was collected to extract genomic DNA.A total of 79 genes related to genetic metabolic diseases, such as ACADSB, IVD and ACADM, were captured by liquid-phase capture technology.High-throughput sequencing and bioinformatics analysis were used to acquire gene variation information and the genes were categorized by American College of Medical Genetics and Genomics classification standard.According to the results of genetic analysis, the newborns with C5 elevation were divided into 3 groups: non-mutation group(11 cases), ACADSB mutation group(16 cases) and IVD mutation group(7 cases). Wilcoxon rank sum test was performed to analyze the difference between these groups. Results:Among 34 neonates, 6 ACADSB variants were detected in 16 cases, and 2 of them [c.461G>A (p.G154E), c.746delC(p.P249Lfs*15)] were novel variants.Eleven IVD variants were detected in 7 cases, and 7 of them [c.118A>G(p.N40D), c.296-10C>G, c.302A>G(p.Y101C), c.537G>A(p.M179I), c.667C>T(p.R223W), c.983A>G(p.K328R), c.1147+ 5G>A] were never reported before.There was no significant difference in the C5 concentration in initial screening among the three groups ( P>0.05). Conclusions:Mutations in ACADSB and IVD genes are the main causes of augmented C5 levels in neonatal screening.For newly discovered genetic variants, functional prediction by multiple bioinformatics analysis software is recommended.And it is also important to carry out clinical follow-up and evaluation.

Research progress on the mechanism of Hippo signaling pathway in organ regeneration / 药学实践与服务

Hippo signal pathway is one of the main signal pathways regulating cell proliferation and apoptosis in multicellular animals, which plays a vital role in the maintenance of tissue homeostasis and the regulation of organ growth. Most mammals have limited regenerative potential, and recent studies have shown that Hippo signal pathway is critical in the regeneration of various tissues and organs. The role of Hippo signaling pathway in organ regeneration and the research progress of related targets were introduced, the mechanism of Hippo signaling pathway promoting regeneration analyzes were aralyzed in this review, which provide theoretical reference for the treatment of diseases related to organ regeneration.

Basic research on toxin of Solenopsis invicta / 药学实践与服务

Solenopsis invicta is a kind of invasive pest that causes serious damage to local agriculture, environment, and human health. They attack mainly with venom within stingers. Those who are allergic to the venom would suffer a systemic anaphylaxis, even fatal shock, after being stinged by these ants. Many studies reveal that their venom is mainly composed by water, insoluble alkaloids and trace proteins, within which alkaloids are the main cause of burning sensation and blisters, while allergic reactions are caused by proteins or peptides. The research progress of toxic substances in the venom of Solenopsis invicta as well as the roles and functions of each component were reviewed in this paper.

Clinical analysis of middle-aged cases of macroencephalic leukoencephalopathy with subcortical cysts / 中华神经科杂志

Megalencephalic leukoencephalopathy with subcortical cysts (MLC, OMIN: 604004) caused by mutations in the MLC1 gene, is an rare autosomal recessive disorder. More patients are with infancy and young children onset, whereas adult cases are rare. Only 2 patients from 1 family have been reported in domestic adult cases. Now a 58-year-old female MLC patient is reported. The clinical manifestations of the patient included large head circumference, slow responses, walking difficulties, seizures and paroxysmal loss of consciousness. The result of whole exome sequencing revealed a homozygous insertion mutation c.920_943dup in the MLC1 gene. The mutation in this patient has not been reported in the Human Gene Mutation Database.

Role of plasma neurofilament protein light chain in diagnosing and differentiating PD and multisystem atrophy-Parkinson subtypes / 中华神经医学杂志

Objective:To investigate the role of plasma neurofilament light chain (NfL) in diagnosing and differentiating Parkinson's disease (PD) and multiple system atrophy-Parkinsonian subtype (MSA-P).Methods:Forty PD patients and 23 MSA-P patients admitted to Department of Neurology, Henan Provincial People's Hospital from June 2019 to December 2021 were recruited; 27 healthy subjects accepted physical examination during the same period were selected as controls. Ultrasensitive Simoa technology was used to measure the plasma NfL. Differences in clinical data and plasma NfL were compared among all subjects. Correlations of plasma NfL with clinical characteristics, such as disease course, Hoehn-Year (H-Y) staging, Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT) and levodopa equivalent daily dosage (LEDD), were analyzed with Pearson correlations. Receiver operating characteristic (ROC) curve was used to analyze the value of plasma NfL in diagnosing and differentiating PD and MSA-P.Results:Compared with MSA-P group, PD group had significantly longer disease course and statistically lower scores of UPDRS-II and SCOPA-AUT ( P<0.05). The plasma NfL in MSA-P group, PD group and healthy control group was decreased successively ([37.69±10.47] pg/mL, [17.85±4.23] pg/mL, [12.86±3.14] pg/mL, respectively), with statistical differences ( P<0.05). In MSA-P patients, Pearson correlations showed positive correlation between plasma NfL and age ( r=0.442, P=0.035); and Partial correlations showed positive correlations between plasma NfL and scores of UPDRS-I and UPDRS-III ( P<0.05), and plasma NfL showed no significant correlation with H-Y staging, UPDRS-III, MoCA, LEDD or SCOPA-AUT scores ( P>0.05). In PD patients, Pearson correlations showed that plasma NfL was positively correlated with age ( r=0.342, P=0.031); partial correlations showed that plasma NfL was positively correlated with H-Y staging and UPDRS-III, and negatively correlated with MoCA scores ( P<0.05); plasma NfL showed no significant correlation with disease course, scores of UPDRS-I and UPDRS-II, LEDD, and SCOPA-AUT scores ( P>0.05). ROC curve showed that the area under the curve (AUC) of plasma NfL in diagnosing PD was 0.814 (95% CI: 0.712-0.920, P<0.001); AUC of plasma NfL in differentiating and diagnosing PD and MSA-P was 0.980 (95% CI: 0.954-1.000, P<0.001); AUC of plasma NfL in diagnosing MSA-P was 0.998 (95% CI: 0.993-1.000, P<0.001). Conclusions:Plasma NfL is correlated with severity of motor symptoms in MSA-P patients; plasma NfL is correlated with cognitive function and disease course in PD patients. Besides, plasma NfL has high sensitivity and specificity in differentiating PD and MSA-P, therefore, plasma NfL could serve as a biomarker to diagnosis and differentiate PD.

Intervention effects and mechanism of Toddalia asiatica on cardiovascular damage in rats with collagen-induced arthritis / 中国药房

OBJECTIVE To investigate the intervention effects and potential mechanism of Miao medicine Toddalia asiatica on cardiovascular damage in rats with collagen-induced arthritis （CIA） based on vitamin D （VD） and neutrophil extracellular traps （NETs）. METHODS SD rats were randomly divided into the normal group （9 rats） and the modeling group （61 rats）. CIA model was prepared by multi-point injection of type Ⅱ bovine collagen+Fisher’s incomplete adjuvant； the model rats were randomly divided into the model group， methotrexate group （positive control， 1.5 mg/kg， twice a week）， vitamin D group [pathway validation， 1 000 IU/（kg·d）， once a day]， T. asiatica low-dose， medium-dose and high-dose groups [0.54， 1.08， 2.16 g/（kg·d）， calculated by crude drug， once a day]， with 9 rats in each group； they were given relevant medicine intragastrically for 4 consecutive weeks. Arthritis index scoring was performed after modeling and before administration， and plantar thickness was measured before and after the last administration； the histopathological changes of ankle joint， heart and abdominal aorta were observed in rats； the serum contents of myeloperoxidase （MPO）， interleukin-6 （IL-6） and 25-hydroxyvitamin D3 [25（OH）D3] were detected； the expressions of peptidylarginine deiminase 4 （PAD4）， NETs markers [citrullinated histone H3（CitH3）， MPO]， VD-related indicators [vitamin D receptor （VDR）， 25-hydroxyvitamin D-1α-hydroxylase （CYP27B1）] and IL-6 were determined in cardiac tissue. RESULTS Compared with the normal group， the plantar thickness of the arthritis index increased significantly in the model group （P＜0.01）. The obvious inflammatory cell infiltration and fibrous tissue hyperplasia were found in the ankle joint， the obvious myocardial fiber （No.2019YFC171250101） vacuoles and thickening of some surrounding blood vessel walls were found in the heart tissue， and the endothelial detachment was found in the abdominal aorta. The contents of MPO and IL-6 in serum increased significantly（P＜0.01），while the level of 25（OH）D3 decreased significantly （P＜0.01）； the protein expressions of PAD4， CitH3， MPO and IL-6 in myocardial tissue up-regulated significantly （P＜0.01）， while protein expression of VDR and CYP27B1 changed to acertain extent without significance （P＞0.05）. Compared with the model group， the pathological changes of ankle joints and cardiac tissue in rats were significantly improved in administration groups， and the above indicators were generally reversed （P＜0.05 or P＜0.01）. CONCLUSIONS T. asiatica can improve rheumatoid arthritis symptoms and cardiovascular damage by inhibiting the formation of NETs and inflammatory response， the mechanism of which may be associated with the regulation of VD expression.

Expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances / 肿瘤研究与临床

Objective:To explore the expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances.Methods:The clinical data of 57 patients diagnosed as pancreatic ductal carcinoma (PDAC) at the Affiliated Cancer Hospital of Xiangya Medical College of Central South University from January 2014 to December 2018 were retrospectively analyzed. The relative expressions of LINC00673 in pancreatic cancer tissues and paracancerous normal tissues (within 3 cm from the edge of cancer tissues) were examined by using quantificational reverse transcription-polymerase chain reaction (qRT-PCR). The ISG15 protein expressions in pancreatic cancer tissues and paracancerous normal tissues were examined by using immunohistochemistry. The difference in LINC00673 expression between ISG15 protein positive and negative patients was compared. The correlation between LINC00673 and ISG15 protein expressions in pancreatic cancer was analyzed by Spearman rank correlation analysis. Moreover, the correlations of LINC00673 and ISG15 protein expressions with clinical stage and pathological classification of pancreatic cancer patients were analyzed.Results:The positive expression of ISG15 protein in pancreatic cancer tissues was 40.4% (23/57), which was higher than that in paracancerous normal tissues [15.8% (9/57)] ( χ2 = 7.90, P = 0.004), and the relative expression of LINC00673 in pancreatic cancer tissues was 0.99±0.36, which was lower than that in paracancerous normal tissues (1.26±0.41) ( t = 4.80, P < 0.001). For 23 (40.4%) ISG15-positive patients and 34 (59.7%) ISG15-negative patients, the relative expression of LINC00673 was 0.77±0.46 and 0.45±0.27 ( P < 0.001). Spearman analysis showed that there was a correlation between LINC00673 and ISG15 protein expressions ( ρ = -0.429, P = 0.001). The relative expression of LINC00673 decreased in patients with low differentiated or undifferentiated tumor, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between LINC00673 expression and patients' age, tumor site, preoperative CA199 level, and TNM stage (all P > 0.05); ISG15 protein expression increased in patients with low differentiated or undifferentiated tumor, TNM stage Ⅲ-Ⅳ, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between ISG15 protein expression and patients' gender, age, tumor site, and preoperative CA199 level (all P > 0.05). Conclusions:The expression of LINC00673 in pancreatic cancer is related to vascular invasion, tumor differentiation degree and lymph node metastasis, and the expression of ISG15 in pancreatic cancer is related to vascular invasion, tumor differentiation degree, lymph node metastasis and TNM stage. The combined detection of LINC00673 and ISG15 protein could be a valuable prognostic indicator for pancreatic cancer. The therapies targeting LINC00673 and ISG15 protein signaling pathways are expected to be a potential option for immunotherapy of pancreatic cancer.

Serotype and drug resistance of 815 Salmonella isolates in Hunan Province / 预防医学

Objective@#To investigate the serotype and drug resistance of 815 Salmonella isolates from Hunan Province, so as to provide insights into management of Salmonella infections.@*Methods@#Salmonella isolates were collected from stool samples of foodborne diarrheal patients and food samples in Hunan Province from 2020 to 2021, and serotyped. Antimicrobial susceptibility test was performed using the broth microdilution method.@*Results@#A total of 10 groups and 39 serotypes were characterized in 815 Salmonella isolates. Among the 646 Salmonella isolates of human sources, 388 isolates were identified as serogroup B (60.06%), with S. typhimurium and its variants aspredominant serotypes (364 isolates, 56.35%), and among 169 foodborne isolates, 61 isolates were characterized as serogroup B (36.09%) with S. london as the predominant serotype (26 isolates, 15.38%). There were 597 antimicrobial resistant Salmonella isolates of human sources, with a drug resistance rate of 92.41%, and the percentage of ampicillin resistance was 81.58%. There were 140 foodborne antimicrobial resistant isolates, with a drug resistance rate of 82.84%, and the proportion of tetracycline resistance was 72.78%. However, Salmonella isolates from both humans and foods were sensitive to imipenem. In addition, there were 577 multidrug resistant Salmonella isolates, including 490 multidrug resistant isolates of human sources and 87 foodborne multidrug resistant isolates.@*Conclusions@#S. typhimurium and its variants and S. london were predominant serotypes of Salmonella isolates from 815 foodborne diarrheal patients and food samples in Hunan Province from 2020 to 2021, and a high rate of multidrug resistance was detected.

Effect of Yinchenhao decoction on renal oxidative stress injury in rats with obstructive jaundice and its mechanism of action based on the nuclear factor erythroid 2-related factor 2 signaling pathway / 临床肝胆病杂志

Objective To investigate the effect of Yinchenhao decoction on renal oxidative stress injury in rats with obstructive jaundice and its association with the regulation of the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear translocation. Methods A total of 32 male Sprague-Dawley rats were randomly divided into sham-operation group (S group), model group (O group), low-dose Yinchenhao decoction group (LY group), and high-dose Yinchenhao decoction group (HY group), with 8 rats in each group. For the rats in the S group, the upper common bile duct was isolated without ligation, and for those in the other groups, double ligation of the middle and upper 1/3 of the common bile duct was performed to establish a model of obstructive jaundice. After 7 days, the rats in the LY group and the HY group were given Yinchenhao decoction by gavage at a dose of 6.3 and 18.9 mL/kg, respectively, while those in the S and O groups were given an equal volume of distilled water by gavage every day for 7 consecutive days, and the rats were treated on day 14. ELISA was used to measure the serum levels of total bilirubin (TBil), direct bilirubin (DBil), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), blood urea nitrogen (BUN), and creatinine (Cr); spectrophotometry was used to measure the activity of the oxidative stress factors superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissue; quantitative real- time PCR and Western blotting were used to measure the mRNA and protein expression levels of Nrf2, Kelch-like ECH-associated protein 1 (Keap1), and NAD(P)H quinone dehydrogenase 1 (NQO1) in renal tissue; immunohistochemistry was used to measure observe the nuclear translocation of Nrf2 protein in renal tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further pairwise comparison within groups. Results Compared with the S group, the O group had significant increases in the levels of TBil, DBil, ALT、GGT, BUN, and Cr, a significant reduction in the activity of SOD, and a significant increase in the level of MDA (all P 0.05). Compared with the S group, the O group had a significant reduction in the positive rate of Nrf2 in cell nucleus in renal tissue ( P < 0.05), and compared with the O group, the LY group and the HY group had a significant increase in the positive rate of Nrf2 in cell nucleus ( P < 0.05). Conclusion Yinchenhao decoction can effectively alleviate renal injury caused by obstructive jaundice, possibly by upregulating the protein expression of Nrf2 in renal tissue and regulating the nuclear translocation of Nrf2 protein, so as to mediate the protein expression of downstream NQO1, regulate oxidative stress response caused by obstructive jaundice, and thereby alleviate renal injury in rats.