Objective:To explore the clinical, imaging, and genetic characteristics of an adult patient with sporadic Neuronal intranuclear inclusion disease (NIID).Methods:A patient who had visited the First People′s Hospital of Chenzhou on August 6, 2023 was selected as the study subject. Results of clinical examination, neuroimaging, and genetic testing were retrospectively analyzed along with a literature review. The number of GGC trinucleotide repeats in the 5′-untranslated region of the NOTCH2NLC gene was determined by GC-PCR. Results:The patient had presented with episodic encephalopathy, with enhanced magnetic resonance imaging showing enhancement features of the posterior cerebral cortex during the period of acute episode. Genetic testing revealed an increased number of GGC repeats ( n = 97) in the 5′- untranslated region of the NOTCH2NLC gene, which confirmed the diagnosis of NIID. Conclusion:Clinical attention should be paid to the enhanced MRI findings of patients with adult-onset NIID, for whom posterior cortical enhancement may be characteristic manifestation during the acute phase of encephalopathy-like episode.

Objective To evaluate the apparent diffusion coefficient(ADC)values of different bone marrow infiltration patterns in multiple myeloma(MM)patients with MR whole-body diffusion weighted imaging(WB-DWI)and to determine the ADC thresholds for different bone marrow infiltration patterns.Methods Nineteen MM patients diagnosed for the first time were selected.The lesions types of each site(cervical spine,ribs,sternum,humerus,scapula,sacral spine,ilium,femur,thoracic spine,and lumbar spine)after the WB-DWI images were visually evaluated,which were divided into focal group(including focal lesion in combined focal and diffuse infiltration)[region of interest(ROI)=141],pure diffuse infiltration group(ROI=150),diffuse lesion in combined focal and diffuse infiltration group(ROI=127),"salt-and-pepper"group(ROI=54),and normal appearance group(ROI=68).ADC values were measured and compared between each group and the receiver operating characteristic(ROC)curve was drawn to distinguish different patterns of bone marrow infiltration.Results There was no statistically significant difference in ADC values between the diffuse lesion in combined focal and diffuse infiltration group and the"salt-and-pepper"group(P＞0.99),and there was statistically significant difference in ADC values between the other groups(P＜0.05).The ROC curve showed that the area under the curve(AUC)for identifying focal group and the"salt-and-pepper"group was 0.889[95％confidence interval(CI)0.844-0.934],the AUC for identifying pure diffuse infiltration group and the normal appearance group was 0.968(95％CI 0.949-0.987).ADC values were able to accurately and visually differentiate between the different patterns of bone marrow infiltration.Conclusion The ADC values can be used as a quantitative tool to objectively distinguish different bone marrow infiltration patterns in MM patients.

Objective:To explore the gene microarray of patients with ankylosing spondylitis in GEO database by using various bioinformatics methods, and to explore the possible targets and mechanisms of action.Methods:The GEO database was searched with "ankylosing spondylitis" the keyword, and the expression profile of genes related to AS was selected as the research object. Standard difference analysis, weighted co-expression analysis and gene set enrichment analysis were conducted to construct the disease set. GO and KEGG enrichment analysis were performed on the disease sets. The NCC algorithm identifies the first five key genes. THP-1 cells were implanted into RPMI-1640 culture medium containing 10% fetal bovine serum to multiply and construct the cell model of AS in vitro. The expression levels of 5 key genes were detected by qRT-PCR and Western blot. The experimental measurement data were expressed as mean± standard deviation, and the t test was used in comparison between the two groups. Results:One thousand six hundred and sixty seven disease genes were analyzed, functional annotation was mainly concentrated in 689 molecular components of cytoplasmic ribosomes, ribosomal subunits, ribosomes, cytoplasmic large ribosomal subunits, the structural composition of ribosomal REDOX enzyme activity, 1 002 molecular functions of NADH dehydrogenase activity, NADH dehydrogenase activity, and 5 764 molecular processes of mRNA catabolism and RNA catabolism The physical process involved 1 002 signaling pathways involved in Alzheimer′s disease, Prion disease, Parkinson′s disease, and the first 5 key genes were identified as RPS11, RPL4, RPL37A, RPS23, and RPS9. The experimental results were obtained by t test. The results showed that TNF-α mRNA ( t=5.59, P=0.001) and protein ( t=20.14, P<0.001) were significantly increased, indicating that LPS had induced inflammatory response in THP-1 cells, while RPL37AmRNA ( t=5.87, P=0.001), RPS11 mRNA ( t=3.88, P=0.008), RPS23 mRNA ( t=2.64, P=0.038), RPL37A protein ( t=3.18, P=0.030), RPS11 protein ( t=11.26, P<0.001), RPS23 protein ( t=5.64, P<0.001), increased, while RPS9 mRNA ( t=3.16, P=0.020), RPL4 mRNA ( t=2.54, P=0.044), RPS9 protein ( t=5.85, P<0.001) and RPL4 ( t=2.93, P=0.040) protein expressions decreased. RPL23 stimulated the joint synovial tissue to produce effect-T lymphocytes and release a large number of IL-2 and other inflammatory cytokines. RPS9 acts on the early stages of ribosomogenesis, and knocking down RPS9 reduced overall protein synthesis. RPL4 interacted with TTC22 protein to enhance the binding of WTAP mRNA to RPL4, which was associated with immune diseases. The nucleoprotein OGFOD1 catalyzed the hydroxylation of RPS23 and participated in the inflammatory process. The chromosome conformation confirmed the single nucleotide polymorphism function of IL23R genomic locus in AS disease. Conclusion:Ribosomal protein may be an important target for exploring the mechanism of AS inflammation.

Objective:To discuss the medication law in prescriptions of Professor Shao Nianfang in the treatment of kidney deficiency and bone marrow loss in senile dementia based on data mining.Methods:Medical cases of kidney deficiency and bone marrow loss in senile dementia in the Geriatric Hospital of Shandong University of Traditional Chinese Medicine from 1st Jan. 2014 to 31st Oct, 2019 were collected. Through hospital electronic medical records system prescription statistics, using ancient and modern medical case cloud platform (V1.2.4), medication frequency, property ans taste, efficacy analysis, correlation rule analysis, clustering analysis and complex network analysis were performed.Results:Totally 110 cases were included in medical cases, involving 238 kinds of Chinese materia medica. The top 10 Chinese materia medica with use frequency were Poria, Acori Tatarinowii Rhizoma, Corni Fructus, Dioscoreae Rhizoma, Rehmanniae Radix Praeparata, Alpiniae Oxyphyllae Fructus, Rehmanniae Radix, Astragali Radix, Chuanxiong Rhizoma, Atractylodis Macrocephalae Rhizoma; the properties were mainly mild, warm slight cold, and cold; the tastes were mainly sweet, bitter, pungent, and light; the meridians were mainly spleen, liver, lung and kidney meridians; the efficacy was clearing dampness and promoting diuresis, clearing heat and promoting blood circulation, calming mind, clearing heat and detoxification, reducing dampness and promote appetizing, tonifying spleen; the association analysis found 15 groups of drug combinations used more than 25 times, they were: Corni Fructus and Poria, Corni Fructus and Dioscoreae Rhizoma, Dioscoreae Rhizoma and Corni Fructus, Rehmanniae Radix Praeparata and Corni Fructus, Dioscoreae Rhizoma and Poria, Astragali Radix and Poria, Alismatis Rhizoma and Poria, Moutan Cortex and Poria, Rehmanniae Radix Praeparata and Poria, Rehmanniae Radix and Poria, Polygalae Radix and Acori Tatarinowii Rhizoma, Moutan Cortex and Corni Fructus, Moutan Cortex and Dioscoreae Rhizoma, Alismatis Rhizoma and Corni Fructus, Alismatis Rhizoma and Dioscoreae Rhizoma; clustering analysis identified four groups of new prescriptions, the first group: Poria, Rehmanniae Radix, Rehmanniae Radix Praeparata, Alismatis Rhizoma, Moutan Cortex, Corni Fructus, Dioscoreae Rhizoma; the second group: Acori Tatarinowii Rhizoma, Cistanches Herba, Morindae Officinalis Radix; the third group: Alpiniae Oxyphyllae Fructus, Chuanxiong Rhizoma, Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle; the fourth group: Atractylodis Macrocephalae Rhizoma, Codonopsis Radix, Astragali Radix, Angelicae Sinensis Radix; the results of complex network analysis showed that the core prescription was modified Liuwei Dihuang Pills. Conclusion:This study found that in view of kidney deficiency and bone marrow loss in senile dementia, Professor Shao pays attention to strengthening the healthy qi, and focuses on tonifying deficiency, taking into account the methods of clearing dampness, clearing heat, detoxification, removing blood stasis and restoring consciousness. The four new prescriptions found in the study can provide a reference for modified medication for syndrome differentiation.

Objective:To investigate the feasibility of echocardiography-guided transcatheter closure of atrial septal defect (ASD) during pregnancy and summarize the multidisciplinary treatment experience for such women.Methods:A retrospective analysis was performed on three women receiving echocardiography-guided secondum ASD closure during pregnancy in Guangdong Provincial People's Hospital from January 2018 to October 2021. Perioperative and perinatal multidisciplinary treatment and prognosis were described.Results:All three patients underwent cardiac ultrasonography due to abnormal electrocardiogram during routine prenatal examination and were diagnosed with secondum ASD. Progressive cardiac dysfunction was found during close follow-ups and all cases met the criteria for ASD closure during pregnancy after multidisciplinary evaluation. Echocardiography-guided ASD closure was successfully performed in all patients. Pulmonary arterial pressure was significantly reduced and the cardiac function was stable after the operation. All patients delivered vaginally at term without complications such as miscarriage, premature birth, postpartum hemorrhage or fetal growth restriction and had their cardiac function recovered during postpartum follow-up.Conclusions:Echocardiography-guided ASD closure during pregnancy is technically feasible. Good maternal and fetal outcomes can be obtained through multidisciplinary and close monitoring and treatment during perioperative and perinatal periods.

Predicting the protein binding rate of drugs in plasma is helpful to us in understanding the pharmacokinetic characteristics of drugs, with much value of reference for early research on drug discovery. In this study, plasma protein binding rate information of 2 452 clinical drugs were collected.Two pieces of software, Molecular Operating Environment (MOE) and Mordred, were used to calculate molecular descriptors, which were used as input features of the model.Extreme gradient boosting (XGBoost) algorithm and random forest (RF) algorithm were then used to build a machine learning model.The results showed that, compared with MOE, the prediction performance of the constructed model was better using the molecular descriptor calculated by Mordred as the input of the model.The prediction performance results of the model constructed using the XGBoost algorithm and the RF algorithm were similar, and the R2 of the optimal model were both 0.715.According to the research results, it can be concluded that the drug plasma protein binding rate is closely related to some physical and chemical properties of the drug molecule, such as water solubility, octanol/water partition coefficient and conjugated double bonds.Using these parameters to predict the plasma protein binding rate of drugs has the advantages of convenience and efficiency, which can provide reference for related pharmacokinetic studies.

[摘 要] 目的：探讨敲减中心体相关激酶2（never in mitosis A-related kinase 2，NEK2）对结直肠癌细胞5-FU化疗敏感性的影响及其可能的机制。方法：采用qPCR和Western blotting检测结直肠癌细胞中NEK2 mRNA及蛋白的表达水平。构建针对NEK2基因的小干扰RNA（siRNA）并转染至结直肠癌细胞HCT116及SW620，实验分为阳性干扰组1（转染NEK2 siRNA1）、阳性干扰组2（转染NEK2 siRNA2）和阴性对照组（转染si-NC），均用5-FU处理。采用CCK-8实验、V-FICT/PI Annexin双染色流式细胞术实验观察敲减NEK2基因对5-FU作用下结肠癌细胞的增殖、周期分布及凋亡的影响，采用Western blotting检测敲减NEK2基因对5-FU作用下结直肠癌细胞内Wnt/β-catenin信号通路相关蛋白表达的影响。结果：NEK2蛋白及mRNA在结直肠癌细胞HCT116、SW620中均呈高表达（P<0.05或P<0.01），转染NEK2 siRNA可高效抑制HCT116、SW620细胞中NEK2蛋白及mRNA表达（均P<0.01）。经不同浓度5-FU作用后，阳性干扰组1和阳性干扰组2的细胞存活率和IC50均显著低于阴性对照组（均P<0.01），细胞发生G0/G1期阻滞且凋亡率显著升高（均P<0.01），胞核β-catenin、c-myc和cyclin D1表达水平显著下降而胞质β-catenin表达水平升高（均P<0.01）。结论：敲减NEK2基因可有效提高人结直肠癌细胞对5-FU的化疗敏感性，该作用可能是通过调控Wnt/β-catenin信号通路相关蛋白表达来实现的。

Objective To evaluate the impact of carvedilol and metoprolol on left ventricular (LV)dyssynchrony in idiopathic dilated cardiomyopathy(IDC).Methods In this study,we randomly assigned 65 IDC patients from January 2009 to June 2011 to re-ceive carvedilol or metoprolol succinate.All patieats were divided in to carvedilol group(n=33)and metoprolol group(n=32)Echo-cardiographic measurements and N-terminal pro-brain natriuretic peptide levels were obtained at baseline and 6 month after thera-py.Then long-term follow up the survival rate of patients were observed.Results In carvedilol group,reduction in LVEDS and in-crease in LVEF was higher compared to metoprolol group.Also improvement in LV dyssynchrony achieved and survival rate with carvedilol was higher than metoprolol.However,Improvements in LV mechanical dyssynchrony was similar in two groups.Im-provements in LV mechanical dyssynchrony achived with both drugs were accompanied by reduction in NT-pro-BNP levels in both carvedilol and metoprolol groups(P >0.05).Conclusion Carvedilol is an effective drug improves the intraventricular dyssynchro-nyfor for IDC patients with left ventricular dyssynchrony,and could increasea the survival rate.

Objective To investigate the effects of alcohol extract of Kunmu decoction on proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). Methods Synovial tissues were obtained from patients with active RA received joint replacement or arthroscopy. The surface antigen and the amount of apoptotic cells were determined by flow cytometry. The inhibitive effect was detected by MTT assay. Results The CD90+surface antigen of synoviocytes was (94.78 ± 0.98)%. The inhibitive effect on the proliferation in all treatment groups were in a time-and dose-dependent manner. The apoptosis rate was increased in a dose-dependent manner among all dosage alcohol extract groups. Conclusion Kunmu decoction might inhibit proliferation and induce apoptosis of RA-FLS.

Objectives To screen the high-risk population of stroke in China using color Doppler flow imaging (CDFI)and to establish a stroke risk prediction model in Chinese population in order to prevent and treat stroke early. Methods Forty-one base hospitals and 715 286 people in the project areas of the first 6 provinces of China conducted routine physical examinations and investigated the related risk factors for cardiocerebrovascular diseases from July 2011 to April 2012 using a cross-sectional study,among them 61 860 patients underwent carotid CDFI screening,and 49 386 of them were high-risk population (exposed to≥3 risk factors). The bilateral common carotid interma-media thickness (IMT),the number of plaques and the degree of carotid stenosis were screened and documented. And whether carotid IMT thickening or not,with or without carotid plaques,and degree of carotid artery stenotic rate 0-49% and≥50% were performed by multivariate logistic regression analysis with the risk factors for stroke,respectively. Results (1)Logistic regression analysis showed that hypertension,atrial fibrillation,smoking,and lack of physical exercise were the independent risk factors for carotid IMT thickening (hypertension:OR,1. 17;95%CI 1. 12-1. 22;atrial fibrillation:OR,1. 15;95%CI 1. 09-1. 21;smoking:OR,1. 13;95%CI 1. 08-1. 17;and lack of physical exercise:OR,1. 12;95%CI 1.08-1. 16). (2)Hypertension,atrial fibrillation, smoking,and diabetes were the independent risk factors for carotid plaque and carotid artery stenosis rate≥50%(carotid plaque,hypertension:OR,1. 55;95%CI 1. 47-1. 62;atrial fibrillation:OR,1. 13;95%CI 1.06-1. 21;smoking:OR,1. 16;95%CI 1. 11-1. 22;and diabetes:OR,1. 30;95%CI 1. 24-1. 37). Carotid stenosis rate≥50%,hypertension:OR,1. 78;95%CI 1.55-2. 03;atrial fibrillation:OR,1. 59;95%CI 1. 39-1. 81;smoking:OR,1. 33;95%CI 1. 20-1. 48;and diabetes:OR,1. 30;95%CI 1. 17-1. 45. Simple obesity did not increase the incidences of carotid atherosclerotic plaque and carotid artery stenosis ≥50%(OR,0. 78, 0.83;95%CI 0. 75-0. 82 ,0. 75-0. 92,respectively). Conclusions Neck vascular ultrasound can be used as a valuable means for screening high-risk population and detecting risk factors of stroke. It has an important clinical significance for the early diagnosis and treatment of carotid atherosclerosis disease.