Objective To explore the application value of fractional anisotropy(FA)analysis of RGB component transformation in different directions of fibers in substantia nigra in Parkinson's disease(PD).Methods There were 35 cases of PD and 37 cases of normal control group.After being performed by brain diffusion tensor imaging(DTI)scanning,the sequence was imported into 3DSlicense 5.6.0,and the diffusion module was used to implement pseudo color mapping based on FA,locate and segment substantia nigra,and use the substantia nigra mask as the tracking starting point.After forming tracing,fibers were imported into DTIANALYSIS 1.51,converting the RGB components into FA values for analysis,and visualized the analysis result.At the same time,fiber length,fiber density,and segmented FA point cloud percentage were compared.Results Compared with the normal group,the length of substantia nigra fibers in the PD group was shorter[(95.14±19.85)mm vs(115.99±21.39)mm,P＜0.01],and there was a statistical difference between the two groups.There was no statistical difference in fiber density[(0.07±0.05)/mm3 vs(0.10±0.12)/mm3,P＞0.05]between control group and PD group.The percentage of FA segment point clouds in the PD group was lower than that in the normal group at 0.9-1,but the principal component characteristics of the point cloud ratios in each FA segment were not significant.Conclusion Based on the transformation of RGB components into FA analysis,the length,density,and FA values of substantia nigra nerve fibers in PD patients can be quantified and visualized,providing a basis for the study of PD neural pathways.

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

Lithium(Li)salts are commonly used as psychotropic medications for the treatment of major depressive disorders.However,long-term use of Li salts poses a high risk of toxicity,necessitating continuous monitoring of Li concentration in patient blood to ensure medication safety,which is crucial for clinical treatment.Laser-induced breakdown spectroscopy(LIBS),as a rapid analytical technique,has been widely applied in the elemental analysis of complex matrices in various practical scenarios.In this study,LIBS technology combined with partial least squares(PLS)was employed for quantitative analysis of Li elements in blood matrix.A total of 45 clinical blood samples were utilized,and the quantitative models for plasma and whole blood matrices were separately investigated.The number of latent variables in the PLS algorithm was optimized using a five-fold cross-validation method.Results revealed that the PLS quantitative model constructed on the basis of plasma matrix achieved a predictive determination coefficient(R2)of 0.992,a predictive root mean square error(RMSEP)of 0.204 μg/mL,and a relative standard error(RSD)of 2.14%.In contrast,for the PLS quantitative model constructed on the basis of whole blood matrix,the R2 was 0.984,the RMSEP was 0.728 μg/mL,and the RSD was 3.45%Consequently,the LIBS model constructed on the basis of plasma calibration values demonstrated superior performance in quantitative analysis of Li element in whole blood,and LIBS technology provided a new possibility for rapid assessment of blood Li levels in clinical practice,with promising prospects for application.

Objective To explore astrocyte activation's impact on cognitive deficits post-traumatic brain injury(TBI).Methods SPF male rats were divided into control,sham-operation and model groups with 10 rats per group.Control group did not receive the surgical intervention;sham-operation group underwent craniotomy without damaging the dura mater;model group was struck with brain injury instrument after craniotomy.The rats with knockout overexpressed glial fibrillary acidic protein(GF AP)gene were set as the knockout group and overexpression group,with 10 rats per group.The knockout and overexpression groups were treated as the model group.Neurological function was evaluated by modified neurological severity score(mNSS).Escape latency was assessed with the Morris water maze test.The expression levels of GFAP in astrocytes were measured quantitative real-time polymerase chain reaction.The positive expression of astrocytes was determined by immunohistochemistry.Results The mNSS of control,sham-operation,model,knockout and overexpression groups were 0,0,(9.60±1.17),(15.20±1.55)and(12.00±1.33)points;the escape latency period at day 7 was(16.15±2.48),(16.98±2.35),(40.72±5.42),(75.42±8.59)and(47.23±6.04)s;the number of positive astrocytes was(1 264.60±135.45),(1 289.20±132.29),(3 269.10±189.39),(103.90±11.09)and(5 301.50±236.29)cell·mm-2;the expression levels of GFAP gene in control,sham-operation,model and overexpression groups were 0.86±0.02,0.92±0.04,1.37±0.07 and 3.42±0.07.Compared with overexpression group,the differences of above indexes in control,sham-operation,model,knockout groups were statistically significant(all P＜0.05).Conclusion TBI causes cognitive impairment and affects cognition and memory in rats,and the GFAP gene is associated with the activation of astrocytes and helps repair nerve damage.

Efficiency in pharmacodynamic study and evaluation is the critical issue in current drug research and development of non-alcoholic steatohepatitis(NASH).Resmetirom,the first marketed medicine for NASH,is approved by pathological surrogate endpoints,meanwhile several clinical trials suspended due to failure to achieve the liver histologic surrogate endpoints.The well-done non-clinical pharmacodynamic study basing on pathological features(ballooning degeneration,lobular inflammation,fibrosis)of NASH,is a great support to the whole research and development projects of new medicines for NASH.In this article,we discussed the necessity and feasibility of the NASH non-clinical pharmacodynamic study combining the clinical trials of NASH drug,the pathological features and the animal models of NASH,in order to facilitate the high-quality research and development of NASH drugs.

Objective:To study the clinical safety and validity of retrograde new endoscopic field of vision in miniature pigs.Methods:6 live miniature pigs were selected as study subjects,En-doscopic Retrograde New View(ERNV)was selected.The performance,image quality and intraoper-ative and postoperative complications were evaluated.To evaluate whether all the experimental ani-mals could complete the relevant endoscopy.Verify ERNV's operating performance,including whether the duodenoscope can enter the biliary tract smoothly,and made sure whether the injection,suction,and instrument channels were unobstructed.Choledochoscope image clarity,color resolu-tion,image deformation and distortion,accurate evaluation of lumen conditions and clear observation of mucosal surface conditions were analyzed.Whether there were operant injuries such as bleeding and perforation,as well as adverse events such as respiratory depression and cardiac arrest.The sur-vival status and adverse reactions of all pigs were observed.Results:The choledochoscope was successfully inserted into the bile duct of 6 miniature pigs.The product had good operation perfor-mance and could enter the bile duct through the duodenoscope smoothly.The injection,suction and instrument channels were relatively smooth.In addition,the endoscopic images are clear,with better color resolution,and without image deformation and distortion,which can realize accurate evaluation of the conditions in the lumen and observe the mucosal surface conditions more clearly.No bile duct stenosis or dilatation occurred in all miniature pigs,and the bile duct mucosa was smooth,without hyperemia and edema,and no abnormal thickening or bending of mucous vessels.During the exami-nation,there were no operational injuries such as bleeding and perforation,and no adverse events such as respiratory depression and cardiac arrest occurred.The vital signs of all miniature pigs tended to be stable after operation,and the survival state was good,and there were no complications such as cholangitis,bleeding and perforation.Conclusion:ERNV has good clinical safety and efficacy,ex-cellent operation performance and excellent image quality,and is worthy of clinical application.

Objective To investigate the application value of indobufen combined with clopidogrel in elderly patients with coronary heart disease after percutaneous coronary intervention(PCI)with aspirin contraindications.Methods Elderly patients with coronary heart disease with aspirin contraindications were selected as study subjects and divided into 2 groups by random number table method.The control group was given oral clopidogrel bisulfate tablet 75 mg,qd;the treatment group was additionally given oral indobufen tablet 200 mg,qd,and both groups were treated for 3 months.Cardiac function indexes,coagulation-fibrinolytic system indexes,platelet function indexes,vascular endothelial function indexes and microcirculation function indexes were compared between the two groups before and after treatment,and the incidence of MACE and adverse drug reactions were analyzed.Results In this trial,39 cases in both the treatment group and the control group were included in the statistical analysis.The total effective rate of treatment group and control group were 94.87％and 79.49％,respectively,and the total effective rate of treatment group were higher than that of control group(P＜0.05).After treatment,the left ventricular ejection fraction(LVEF)of treatment group and control group were(57.13±3.16)％and(55.65±3.01)％,and the left ventricular end-diastolic volume index(LVEDVI)were(61.29±3.46)and(63.78±3.12)mL·m-2,respectively;the cardiac index were(3.68±0.31)and(3.41±0.28)L·min-1·m-2,and the stroke output index(SVI)were(57.37±2.57)and(55.29±2.74)mL·m-2,respectively;plasminogen activator inhibitor-1(PAI-1)levels were(46.29±4.18)and(49.37±5.24)ng·mL-1;antithrombin Ⅲ(AT-Ⅲ)levels were(131.04±10.65)％and(120.95±9.73)％,respectively;tissue plasminogen activator(t-PA)levels were(0.54±0.09)and(0.46±0.10)U·mL-1;fibrinogen(FIB)levels were(3.52±0.61)and(4.03±0.59)g·L-1,respectively;PT were(15.43±0.65)and(14.92±0.57)s,respectively.Compared with control group,the above indexes in treatment group were statistically significant(all P＜0.05).In the treatment group,there were 1 case of malignant arrhythmia in the cardiovascular adverse event(MACE),and in the control group,there were 2 cases of acute myocardial infarction,3 cases of malignant arrhythmia,2 cases of target vessel revascularization,and 1 case of acute thrombus in the stent.The incidence of MACE in the treatment group and the control group were 2.56％and 20.51％,respectively;the difference were statistically significant(P＜0.05).Conclusion In elderly patients with coronary heart disease contraindicated with aspirin after PCI,indobufen combined with clopidogrel can improve the cardiac function and microcirculation function,improve coagulation and fibrinolysis function,reduce vascular endothelial function injury,and reduce the incidence of MACE.

Objective To investigate the high-frequency ultrasonic anatomical features of the adjacent C7 transverse process and its clinical value in stellate ganglion block(SGB).Methods High-frequency ultrasound was applied to obtain ultrasonographic anatomical sonogram features in the plane of bilateral C7 transverse processes in 52 cases(104 sides in total)of healthy adults and then stored for the operator to learn and correctly label each tissue structure.Fifty patients who underwent ultrasound-guided SGB were selected and divided into the BC7 group(25 cases before study)and AC7 group(25 cases after study).The operation time,SGB success rate,number of adjusted needle tips,dosage of anaesthetic and adverse reaction of patients in both group were recorded.Results The main muscles observed in the C7 plane were the longissimus and anterior scalene muscles,the ultrasonographic anatomical relationships of the vagus nerve located in the carotid sheath,the pleura located posterior to the subclavian artery,and the recurrent laryngeal nerve located in the vicinity of the branches of the inferior thyroid artery are described,and the stellate ganglion was illustrated as a flattened hypoechogenic structure visible on the deep surface of the prevertebral fascia in the region of the external cervical longissimus muscle,vertebral artery and vein,and the medial aspect of the anterior oblique muscle,and emanated the sonographic features of several hypoechoic nerve bundles.Ultrasound guided SGB was completed uneventfully in patients of both groups,and all patients developed Horner syndrome,with the SGB success rate of 100%.The operation time[(5.36±1.11)minutes]of patients in the BC7 group was longer than that in the AC7 group[(3.08±0.86)minutes],the number of adjusted needle tips[(4.20±1.00)times]of patients in the BC7 group was more than that in the AC7 group[(2.24±0.87)times],and the dosage of anaesthetic[(1.82±0.28)mL]of patients in the BC7 group was more than that in the AC7 group[(1.64±0.22)mL],all the differences were statistically significant(P<0.05).There was no significant difference in the incidence of adverse reaction between the two groups(P>0.05).Conclusion After ultrasonic learning of adjacent structures through C7 transverse process,SGB is safe and easy to perform.

Lithocarpus litseifolius is rich in the chalcones phloridzin and trilobatin, the biosynthesis pathways of which have not been fully demonstrated. Chalcone synthase(CHS) is the first key rate-limiting enzyme in the biosynthesis of flavonoids in plants. To explore the functions of CHS gene family in chalcone synthesis of L. litseifolius, this study screened out two CHS genes(LlCHS1 and LlCHS2) from the transcriptome data of this plant, and then bioinformatics analysis and functional characterization were performed for the two genes. The bioinformatics analysis showed that LlCHS1 and LlCHS2 were acidic hydrophilic stable proteins with no transmembrane domain, composed of 395 and 390 amino acid residues, respectively. Both of them contained the characteristic amino acid sequence "WGVLFGFGPGL" and highly conserved active sites(Cys-164, Phe-215, His-303, and Asn-336) of the CHS family. The phylogenetic tree showed that LlCHS1 shared the same clade with similar genes in Aquilaria sinensis, and LlCHS2 was closely related to similar genes in Malus domestica. Under exogenous addition of phloretic acid, co-expression of LlCHS1 or LlCHS2 with Aa4CL from Aromatoleum aromaticum in Escherichia coli catalyzed the production of phloretin from phloretic acid. This study laid a theoretical foundation for revealing the functions of CHS in plants and provided new enzymatic modules for producing phloretin by synthetic biology.
Acyltransferases/chemistry* ; Phylogeny ; Plant Proteins/chemistry* ; Cloning, Molecular ; Amino Acid Sequence