Objective To investigate the influence of type 2 diabetes mellitus(T2DM)on cognitive function and the effective connectivity with in the default mode network(DMN)in the brain.Methods A total of 93 hospitalized patients diagnosed with T2DM were enrolled in this study as T2DM group from The First Affiliated Hospital of Guangzhou University of Chinese Medicine during September 2021 to December 2022.Simultaneously,108 healthy individuals were recruited from the community as normal control(NC)group.The cognitive functions were evaluated in the two groups.A random dynamic causal modeling approach was employed to analyze the effective connectivity within DMN in both groups.Additionally,Pearson correlation analysis was performed to examine the association between differential connectivity,clinical indicators,and cognitive scores in both groups.Results In comparison to the NC group,T2DM individuals exhibited statistically significant reductions in scores in the auditory verbal learning test(AVLT)for immediate recall and the digit symbol substitution test(DSST)(P＜0.05).Additionally,they displayed a notable decrease in effective connectivity from the left lateral parietal cortex(LLPC)to the posterior cingulate cortex(PCC),as well as from the LLPC to the right lateral parietal cortex(RLPC)within the DMN(P＜0.05).Pearson correlation analysis unveiled a negative association between HbA1c levels and the strength of effective connectivity from LLPC to PCC.Conversely,a positive correlation was observed between AVLT(immediate)scores and the strength of effective connectivity from LLPC to PCC and LLPC to RLPC.Additionally,DSST scores displayed a positive correlation with the strength of effective connectivity from LLPC to PCC(P＜0.05).Conclusion Patients with T2DM display compromised effective connectivity from LLPC to PCC and LLPC to RLPC within the DMN network,and this alteration may associated with cognitive impairment.

Ulcerative colitis （UC） is a chronic non-specific digestive disease with abdominal pain， diarrhea， and blood and mucus in stool as the main clinical manifestations and inflammatory injury of colorectal mucosa and submucosa as the main pathological changes. With the change in living habits and dietary structure of people， the incidence and cancer morbidity in UC are rising rapidly all over the world， which has seriously reduced the quality of life and caused a huge social burden. Till now， the pathogenesis has not been elucidated. In western medicine， aminosalicylates， corticosteroids， and immunosuppressors are commonly used to relieve symptoms. However， the long-term application will lead to problems such as decreased efficacy and increased adverse reactions. There are more studies of traditional Chinese medicine （TCM） in the treatment of UC by reducing the inflammatory response， alleviating oxidative stress， protecting the intestinal mucosal barrier， and regulating intestinal microecological imbalance by virtue of the advantages of integrated regulation based on multiple links， levels， and targets. In view of this， the present study reviewed the effect and mechanism of active ingredients of TCM， TCM extracts， TCM pairs， classic TCM compounds， and TCM combined with chemical agents in the treatment of UC based on relevant research articles in recent 10 years to provide references for seeking effective drugs.

Objective:To investigate the value of the 8-channel eye surface phased array coil in improving image quality and demonstrating ocular masses on 3.0 T MR scanner.Methods:From July 2018 to January 2020, the data of orbital MRI in 692 patients with ocular masses on 6 medical centers were prospectively collected. The patients were simple randomly assigned into 8-channel eye surface phased array coil group (413 patients) or 8-channel head phased array coil group (279 patients), with the same MRI sequences. The signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated in orbital anatomy structures and masses (eyelid mass, intraocular mass, lacrimal mass and orbital mass). The image quality scores including motion artifact, mass margin, the relationship between the mass and adjacent structures, and overall image quality were recorded. The differences of image quality between the two groups were compared by two independent sample t-test or Wilcoxon rank test. Results:The SNR and CNR were higher in eye surface coil group than those in head coil group ( P<0.05). The scores of ocular movement artifacts were higher in head coil group than those in surface coil group ( P<0.05). The scores of intraocular mass margin, the relationship between the mass and adjacent structures, and overall image quality were higher in surface coil group than those in head coil group ( P<0.001). There were no significant differences in mass margin, the relationship between the mass and adjacent structures, and overall image quality scores of eyelid, lacrimal gland, and orbital mass between the two groups ( P>0.05). Conclusion:3.0 T MR scanner combined with the 8-channel eye surface phased array coil can improve the SNR and CNR of orbital MR images, the demonstration of the intraocular mass margin and the relationship between the mass and adjacent structures.

Objective:To investigate the value of periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) in improving ability of demonstrating ocular masses on 3.0 T MR scanner.Methods:This study was a multi-center prospective study involving 6 centers. From July 2018 to January 2020, totally 413 patients with ocular masses from 6 centers were prospectively enrolled, and all of them underwent T 1WI and T 2WI, PROPELLER T 1 FLAIR and T 2WI, and contrast-enhanced scans. The signal intensity of eyelid, vitreous body, lacrimal gland, intraorbital segment of optic nerve, and orbital masses of eyelid, intraocular, lacrimal gland and retrobulbar were measured by two radiologists, and the signal to noise ratio (SNR) and contrast noise ratio (CNR) were calculated. The 5-point scoring method was used to evaluate the motion artefacts, tumor edges and the relationship between the tumor and adjacent structures, and the overall score of image quality was calculated. Paired t-test or Wilcoxon signed rank test was used to compare the image quality between PROPELLER and non-PROPELLER images. Results:The SNR and CNR of PROPELLER T 2WI were higher than those of non-PROPELLER T 2WI (all P<0.001). The SNR and CNR of PROPELLER T 1 FLAIR were lower than those of non-PROPELLER T 1WI (all P<0.05). The scores of artefacts and overall image quality in PROPELLER images were higher than those in non-PROPELLER images (all P<0.001). The tumor edge and the relationship between the tumor and adjacent structures scores of eyelid, intraocular, and lacrimal gland masses in PROPELLER images were higher than those in non-PROPELLER images (all P<0.001),while compared to non-PROPELLER images, retro-global masses in PROPELLER images showed no significant differences (all P>0.05). Conclusion:PROPELLER can reduce ocular motion artefacts, effectively improve image quality and ability of demonstrating anterior (eyelid, intraocular, and lacrimal gland) masses.

Objective To explore the value of axis shift between the baseline normal sinus rhythm (NSR) and WCT in diagnosis of wide QRS-complex tachycardia (WCT). Methods 390 surface ECGs of 186 patients with WCT were obtained from April 2012 to April 2018 at Ningbo Medical Center Lihuili Hospital at which the arrhythmia diagnosis was proven by intracardiac electrophysiological study. The axis shift between the baseline NSR and WCT was calculated by table lookup method. Then we analyzed the role of axis shift in diagnosis of WCT. Results Among the 186 patients with WCT, 147 (79.03％) were ventricular tachycardia (VT) , and 39 (20.97％) were supraventricual tachycardia (SVT) with conduction abnormalities. In the 95％ confidence interval, the axis shift showed an outstanding discrimination performance. The area under the ROC curve is 0.708 (0.579-0.817, P =0.007). Compared with left axis deviation, right axis deviation, the right axis deviation of LBBB morphology, the axis shift> 68 degree is more sensitive (53.06％) , and the specificity (91.43％) is also more desirable. Moreover, if the axis shift set> 130 degree, the specificity can reach 100％, and the sensitivity (12.24％) is equivalent to northwestern axis. Conclusion A significant axis shift between the baseline NRS and WCT can distinguish WCT accurately. Given the ease of grasping, it can probably be feasible to popularize as a routine diagnosis method for WCT in primary hospitals.

Objective:To explore the macroporous resin adsorption and the membrane separation technologies for the purification of saponins water extract of Anemarrhena asphodeloides. Methods:Ten-fold amount of water was used to extract twice for 120 min each time to extract saponins from Anemarrhena asphodeloides. The macroporous resin adsorption(HP-20,HPD-600,D101,AB-8) and the membrane separation technologies (ceramic microfiltration membranes 0.8 μm and 0.05 μm, and hollow fiber ultrafiltration mem-branes 50,10 and 6 kDa) were adopted to purify the saponins water extract liquid. The physicochemical parameters including electri-cal conductivity,viscosity and turbidity were measured,as well as the contents of total saponins,proteins and polysaccharides were de-termined. Results:The viscosity and turbidity decreased,the value of pH increased and the electrical conductivity of the saponins puri-fication liquid changed irregularly after the membrane filtration. The microfiltration membrane was more advantageous than the ultrafil-tration membrane in removing macromolecular substances. The smaller the pore diameter of microfiltration membrane, the smaller the intercepted molecular weigh,the higher the removal ratio of proteins and the higher the penetration rate of the total saponins,while the polysaccharides content was stable, which was consistent with the results of physicochemical parameters. The ceramic microfiltration membrane could obtain clearer extract,while the ultrafiltration membrane was more suitable for the enrichment of saponins when the in-tercepted molecular weight was 6 kDa. The macroporous resin HPD-600 was the best for the purification of timosaponin water extraction liquid.Conclusion:The selection of membrane for the separation and purification of different substances is particularly important. The change of physicochemical parameters and the content decrease of macromolecular substances have obvious corresponding relationship. Ultrafiltration membrane is better than microfiltration membrane for the purification of timosaponin water extract liquid.

OBJECTIVETo analyze the hematological and genetic characteristics of unstable hemoglobin Rush (Hb Rush) and compound heterozygote of Hb Rush and thalassemia.

METHODSPeripheral blood samples and genomic DNA from three patients (including two ethnic Dai and one Han Chinese) with anemia of undetermined origin were collected. Hematological phenotypes of these patients were determined through red blood cell analysis and hemoglobin electrophoresis. Genotypes of alpha- and beta-globin genes, -158 XmnⅠ polymorphic site ofγ promoter region, and haplotypes of 7 polymorphic restriction sites in the beta-globin gene cluster were determined using PCR-based methods and DNA sequencing.

RESULTSAll patients have presented hypochromic microcytic anemia and hemoglobin fraction with significant increased measurement (30.5%-59.2%) in the region of fetal hemoglobin during alkaline medium electrophoresis. DNA analysis suggested that all patients have carried mutations leading to the unstable hemoglobin Rush (HBB codon 101, GAG>CAG, Glu>Gln). Two of them were compound heterozygotes of Hb Rush and thalassemia mutations of -α,CD17 and Hb E, respectively. Hb Rush mutation was associated with various haplotypes of the β-globin gene cluster. No significant association was found between increased abnormal hemoglobin fraction in the region of Hb F and the polymorphism ofγ promoter or large deletion of the beta-globin gene cluster.

CONCLUSIONThis study has confirmed the distribution of Hb Rush among various Chinese populations and is the third report of its kind. Hb Rush can result in increased measurement of hemoglobin fraction in the region of fetal hemoglobin (Hb F) during routine hemoglobin electrophoresis under alkaline condition. Hb Rush heterozygote alone can lead to hypochromic microcytic anemia and thalassemia-like phenotype. Prenatal diagnosis of Hb Rush is necessary for carriers.

Adult ; Base Sequence ; Blood Protein Electrophoresis ; methods ; Female ; Fetal Hemoglobin ; genetics ; metabolism ; Genotype ; Haplotypes ; Hemoglobins, Abnormal ; genetics ; metabolism ; Heterozygote ; Humans ; Infant ; Mutation ; Phenotype ; Polymorphism, Genetic ; Sequence Analysis, DNA ; methods ; Thalassemia ; blood ; diagnosis ; genetics ; Young Adult ; alpha-Globins ; genetics ; metabolism ; beta-Globins ; genetics ; metabolism

AIM:We investigated how AT 1-R stimulated by mechanical stresses induces cardiac fibrosis .METHODS:We produced in vivo cardiac pressure overload model in angiotensinogen knockout ( ATG-/-) mice and in vitro mechanically-stretched cell model in cultured neonatal cardiac cells of ATG-/-mice both lack the participation of Ang II .RESULTS: Pressure overload for 4 weeks in ATG-/-mice induced myocardial hypertrophy accompanied by the significant interstitial fibrosis , however , the TGF-β, a key regulatory factor of fibrosis, was not significantly increased in these ATG-/-mice.Meanwhile, the inhibitor for AT1-R significantly inhibited mechani-cal stress-induced cardiac fibrosis in these ATG-/-models whereas inhibition of TGF-βdid not.CONCLUSION:The results showed that mechanical stress-induced fibrotic responses through AT 1-R required the phosphorylation of Smad 2 but not the involvement of TGF-β.

9α-hydroxy-4-androstene-3,17-dione (9-OH-AD) is an important intermediate in the steroidal drugs production. 3-ketosteroid-9α-hydroxylase (KSH), a two protein system of KshA and KshB, is a key-enzyme in the microbial steroid ring B-opening pathway. KSH catalyzes the transformation of 4-androstene-3,17-dione (AD) into 9-OH-AD specifically. In the present study, the putative KshA and KshB genes were cloned from Mycobacterium smegmatis mc(2)155 and Gordonia neofelifaecis NRRL B-59395 respectively, and were inserted into the expression vector pNIT, the co-expression plasmids of kshA-kshB were obtained and electroporated into Mycobacterium sp. NRRL B-3805 cells. The recombinants were used to transform steroids, the main product was characterized as 9α-hydroxy-4-androstene-3,17-dione (9-OH-AD), showing that kshA and kshB were expressed successfully. Different from the original strain Mycobacterium sp. NRRL B-3805 that accumulates 4-androstene-3,17-dione, the recombinants accumulates 9α-hydroxy-4-androstene-3,17-dione as the main product. This results indicates that the putative genes kshA, kshB encode active KshA and KshB, respectively. The process of biotransformation was investigated and the results show that phytosterol is the most suitable substrate for biotransformation, kshA and kshB from M. smegmatis mc(2)155 seemed to exhibit high activity, because the resultant recombinant of them catalyzed the biotransformation of phytosterol to 9-OH-AD in a percent conversion of 90%, which was much higher than that of G. neofelifaecis NRRL B-59395. This study on the manipulation of the ksh genes in Mycobacterium sp. NRRL B-3805 provides a new pathway for producing steroid medicines.
Androstenedione ; analogs & derivatives ; biosynthesis ; Bacterial Proteins ; genetics ; metabolism ; Biotransformation ; Ketosteroids ; Mixed Function Oxygenases ; genetics ; metabolism ; Mycobacterium ; metabolism ; Mycobacterium smegmatis ; enzymology ; Plasmids

OBJECTIVETo analyze the clinical manifestations and intervention against fulminant scrub typhus-associated hemophagocytic syndrome.

METHODThe medical records for the onset time of hemophagocytic syndrome, the clinical course, the chest radiographic findings, laboratory data, antibiotic therapy, clinical outcome and its prognosis were retrospectively reviewed.

RESULT(1) Four patients were diagnosed as scrub typhus based on clinical manifestations only, while 15 patients met the criteria of laboratory diagnosis. All 19 patients with scrub typhus had hemophagocytic syndrome. Eschar lesion was identified in 12 patients, 7 patients were described as an ulcer. A seasonal pattern (78.9% from June through September in 15 patients) was observed. Clinical misdiagnosis was common (all 19 cases). There were 9 patients with admitting diagnosis of scrub typhus, 10 patients were not diagnosed as scrub typhus after admission. In 5 cases within 3 days after admission diagnosis was corrected as scrub typhus. Until discharge from the hospital, 5 cases were not diagnosed with scrub typhus. In this study, the length of time from the illness onset (beginning of fever) to the occurrence of clinical symptoms was (9 ± 4) days. (2) All 19 patients had changed AST levels (149 ± 37) U/L, albumin levels (23 ± 4) g/L, C-reactive protein levels (103 ± 51) mg/L, and platelet count (48 ± 41) × 10⁹/L; bone marrow aspiration revealed in 16 patients marked hemophagocytosis. Weil-Felix agglutination test revealed positive results in 6 of 15 cases. Diagnostic IFA results were positive for 14 patients; 19 patients had interstitial pneumonitis and 17 patients had pleural effusion. (3) Five cases with failure to diagnose the disease had ineffective antibiotics treatment (imipenem or β-lactam-based regimens). These patients did not receive appropriate treatment with antibiotics against scrub typhus. Fourteen patients with admitting diagnosis of scrub typhus were successfully treated with appropriate antibiotics, 8 cases with chloramphenicol, 3 cases with azithromycin, and in 3 patients (2 cases of azithromycin and one case of erythromycin), therapy was then switched to chloramphenicol. Four patients were treated with methylprednisolone and 10 patients with dexamethasone. (4) During their hospitalization, the clinical course in five cases with failure to diagnose the disease rapidly developed and progressed to the life-threatening MODS, four of five cases died. However, the course in 14 patients were relieved and did not progress to MODS.

CONCLUSIONThe diagnosis of scrub typhus was frequently delayed, the early course of scrub typhus could be associated with hemophagocytic syndrome. Serious complications of MODS generally occur without antibiotic treatment. Scrub typhus-associated hemophagocytic syndrome should be taken into consideration among patients with acute systemic febrile illness, significant increases in levels of CRP, hypoalbuminemia, thrombocytopenia, splenomegaly, pneumonitis with pleural effusion, especially those with suspected exposure history. It was not easily recognized without careful observation and was present for a few days in each patient.

Anti-Bacterial Agents ; therapeutic use ; Azithromycin ; therapeutic use ; C-Reactive Protein ; analysis ; Clinical Laboratory Techniques ; Diagnosis, Differential ; Erythromycin ; therapeutic use ; Humans ; Imipenem ; therapeutic use ; Lymphohistiocytosis, Hemophagocytic ; epidemiology ; Pneumonia ; Retrospective Studies ; Scrub Typhus ; diagnosis ; drug therapy ; epidemiology