Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer's disease (AD). The blood-brain barrier (BBB) is essential for keeping toxic substances from entering brain tissues. However, the effect of P. gingivalis bacteremia on BBB permeability and its underlying mechanism remains unclear. In the present study, rats were injected by tail vein with P. gingivalis three times a week for eight weeks to induce bacteremia. An in vitro BBB model infected with P. gingivalis was also established. We found that the infiltration of Evans blue dye and Albumin protein deposition in the rat brain tissues were increased in the rat brain tissues with P. gingivalis bacteremia and P. gingivalis could pass through the in vitro BBB model. Caveolae were detected after P. gingivalis infection in BMECs both in vivo and in vitro. Caveolin-1 (Cav-1) expression was enhanced after P. gingivalis infection. Downregulation of Cav-1 rescued P. gingivalis-enhanced BMECs permeability. We further found P. gingivalis-gingipain could be colocalized with Cav-1 and the strong hydrogen bonding between Cav-1 and arg-specific-gingipain (RgpA) were detected. Moreover, P. gingivalis significantly inhibited the major facilitator superfamily domain containing 2a (Mfsd2a) expression. Mfsd2a overexpression reversed P. gingivalis-increased BMECs permeability and Cav-1 expression. These results revealed that Mfsd2a/Cav-1 mediated transcytosis is a key pathway governing BBB BMECs permeability induced by P. gingivalis, which may contribute to P. gingivalis/virulence factors entrance and the subsequent neurological impairments.
Animals ; Rats ; Bacteremia/metabolism* ; Blood-Brain Barrier/microbiology* ; Caveolin 1/metabolism* ; Gingipain Cysteine Endopeptidases/metabolism* ; Permeability ; Porphyromonas gingivalis/pathogenicity* ; Transcytosis ; Virulence Factors/metabolism*

BACKGROUND: Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia. METHODS: This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years. RESULTS: A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group. CONCLUSIONS In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.
Child, Preschool ; Exchange Transfusion, Whole Blood/adverse effects* ; Humans ; Hyperbilirubinemia, Neonatal/therapy* ; Infant ; Infant, Newborn ; Kernicterus/therapy* ; Phototherapy/methods* ; Retrospective Studies

BACKGROUND: Scleroderma is a multisystem disease in which tissue fibrosis is caused by inflammation and vascular damage. The mortality of scleroderma has remained high due to a lack of effective treatments. However, exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs)-Ex have been regarded as potential treatments for various autoimmune diseases, and may also act as candidates for treating scleroderma. METHODS: Mice with scleroderma received a single 50 lg HUMSCs-Ex. HUMSCs-Ex was characterized using transmission electron microscopy, nanoparticle tracking analysis and nanoflow cytometry. The therapeutic efficacy was assessed using histopathology, immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay and western blot. RESULTS: HUMSCs-Ex ameliorated the deposition of extracellular matrix and suppressed the epithelial-mesenchymal transition process, and the effects lasted at least three weeks. In addition, HUMSCs-Ex promoted M1 macrophage polarization and inhibited M2 macrophage polarization, leading to the restoration of the balance of M1/M2 macrophages. CONCLUSION We investigated the potential antifibrotic and anti-inflammatory effects of HUMSCs-Ex in a bleomycininduced mouse model of scleroderma. So HUMSCs-Ex could be considered as a candidate therapy for scleroderma.

Objective:To evaluate any effect of transcranial pulsed current stimulation (tPCS) on the motor functioning of rats modelling stroke using the Catwalk gait analysis system.Methods:A stroke model was induced in 24 rats using middle cerebral artery embolization. They were then randomly divided into a sham operation group, a model group and a tPCS group, each of 8. Neurological deficit scores were assigned 1 day after the modeling. Beginning two days after the modeling the tPCS group was given 20 minutes of tPCS daily with an intensity of 0.2mA at 10Hz for 7 days. Gait data were collected using the Catwalk gait system 1 day before, as well as 1 and 9 days after the modeling.Results:Nine days after the modeling the average Bederson neuroethology score of the tPCS group was significantly lower than one day after the modelling and significantly lower than the model group′s average. One day after the modelling significant differences were observed in the model and tPCS groups in the average contact area of the affected limb′s paw prints, limb swing speed, stride length, limb speed, swing time, average running speed and standing time compared with before the operation. After nine days the average standing time on the affected fore and hind limbs, as well as the paw contact areas were significantly better in the tPCS group than in the model group.Conclusion:tPCS can promote improvements in gait after ischemia and reperfusion, at least in rats.

Objective: To analyze the clinical phenotype of a Chinese pedigree affected with Tuberous sclerosis complex(TSC) and explore pathogenic mutations of TSC1 and TSC2 gene. Methods: Unique clinical phenotypes, the results of imaging, examination of the proband and special family history, collectively, made the constellation of features of TSC.Genomic DNA was obtained from six affected and eight unaffected members of the family and potential mutations of the TSC1 and TSC2 genes were detected by PCR-amplification of the exons and exon-intron boundaries and direct sequencing.A total of 150 normal unrelated individuals were used as controls. Results: Genetic analysis documented the presence of a heterozygous mutation, c. 1781_1782delTG (p.Val594GlyfsX11), in the exon 15 of TSC1 gene within all the patients of the family. This mutation was not observed in the eight unaffected family members or in the 150 unrelated control subjects from the same population , or the Human Gene Mutation Database(HGMD)and had completely co-segregated with the disease phenotype in the family. Conclusions The c. 1781_1782delTG mutation of TSC1 gene may be responsible for the tuberous sclerosis complex in this family. The data presented in the present study are of significance to clinicians, as well as genetic counselors, and may provide new clues for molecular diagnosis of this disease.

OBJECTIVE: To analyze the clinical phenotype of a Chinese pedigree affected with Tuberous sclerosis complex (TSC) and explore pathogenic mutations of TSC1 and TSC2 gene. METHODS: Unique clinical phenotypes，the results of imaging, examination of the proband and special family history, collectively, made the constellation of features of TSC. Genomic DNA was obtained from six affected and eight unaffected members of the family and potential mutations of the TSC1 and TSC2 genes were detected by PCR-amplification of the exons and exon-intron boundaries and direct sequencing. A total of 150 normal unrelated individuals were used as controls. RESULTS: Genetic analysis documented the presence of a heterozygous mutation, c.1781_1782delTG (p.Val594GlyfsX11), in the exon 15 of TSC1 gene within all the patients of the family. This mutation was not observed in the eight unaffected family members or in the 150 unrelated control subjects from the same population , or the Human Gene Mutation Database (HGMD) and had completely co-segregated with the disease phenotype in the family. CONCLUSION The c.1781_1782delTG mutation of TSC1 gene may be responsible for the tuberous sclerosis complex in this family. The data presented in the present study are of significance to clinicians, as well as genetic counselors, and may provide new clues for molecular diagnosis of this disease．.
DNA Mutational Analysis ; Humans ; Mutation ; Pedigree ; Tuberous Sclerosis ; genetics ; Tuberous Sclerosis Complex 1 Protein ; genetics ; Tuberous Sclerosis Complex 2 Protein

Objective To investigate the impact of deep machine learning Pixel Shine (PS) algorithm on image quality of abdominal low-dose plain CT scanning in BMI≥25 kg/m2 patients.Methods A total of 59 patients (BMI≥25 kg/m2) who underwent abdominal CT scan were collected.The patients were divided into group A (100 kVp,n=30) and B (120 kVp,n=29) according to the tube voltage.According to different reconstruction algorithms and treatment methods,patients in group A were divided into A1 (FBP),A2 (FBP+PS),A3 (50％ASiR-V) and A4 (50％ASiR-V+PS) subgroups,while in group B were divided into B1 (FBP) and B2 (50％ASiR-V) subgroups.CT and SD values of right hepatic lobe and right erector spinae were measured,then SNR and CNR of liver and CT dose index of volume (CTDIvol) were calculated.The consistency of parameters measured by two observers was evaluated.Results The consistency of parameters measured by two observers was good (all ICC＞0.80).There was no statistical difference of CT values of liver and erector among A1-A4 subgroups (all P＞0.05),whereas statistical differences of SD values of liver and erector spinae,also of SNR and CNR of liver were found (all P＜0.001).Among A1-A4 subgroups,SDA4 ＜SDA2 ＜SDA3 ＜SDA1,SNRA4 ＞SNRA2 ＞SNRA3 ＞ SNRA1 (all P＜0.001) was observed.There was no significant difference of CNR between A1 and A3 subgroup (P=0.078),while CNRA4＞ CNRA2＞ CNRA3 or CNRA1 (P＜0.001) was noticed.SD values of the liver in subgroup A2 was lower than subgroup B1,and A4 was lower than B2 subgroup (all P＜0.001),and SNR and CNR increased significantly in A2 and A4 subgroups (all P＜0.001).CTDIvol of group A was lower than that of group B (P＜0.001).Conclusion Deep machine learning PS algorithm can improve image quality of abdominal low-dose plain CT scanning in high-BMI patients.

With the increasing number of immunocompromised hosts, the epidemiological characteristics of fungal infections have undergone enormous changes worldwide, including in China. In this paper, we reviewed the existing data on mycosis across China to summarize available epidemiological profiles. We found that the general incidence of superficial fungal infections in China has been stable, but the incidence of tinea capitis has decreased and the transmission route has changed. By contrast, the overall incidence of invasive fungal infections has continued to rise. The occurrence of candidemia caused by Candida species other than C. albicans and including some uncommon Candida species has increased recently in China. Infections caused by Aspergillus have also propagated in recent years, particularly with the emergence of azole-resistant Aspergillus fumigatus. An increasing trend of cryptococcosis has been noted in China, with Cryptococcus neoformans var. grubii ST 5 genotype isolates as the predominant pathogen. Retrospective studies have suggested that the epidemiological characteristics of Pneumocystis pneumonia in China may be similar to those in other developing countries. Endemic fungal infections, such as sporotrichosis in Northeastern China, must arouse research, diagnostic, and treatment vigilance. Currently, the epidemiological data on mycosis in China are variable and fragmentary. Thus, a nationwide epidemiological research on fungal infections in China is an important need for improving the country's health.
Animals ; China ; epidemiology ; Fungi ; genetics ; pathogenicity ; Genotype ; Humans ; Incidence ; Mycoses ; epidemiology ; transmission

OBJECTIVETo observe and evaluate the clinical efficacy of transcutaneous vagus nerve stimulation (taVNS) at auricular concha for primary insomnia (PI) and affective disorder.

METHODSA total of 35 patients who met the diagnosis standard of PI in(5th edition) were included. The self-developed auricular vagus nerve stimulator (TENS-200A) was applied at auricular concha, 30 min per treatment, twice a day, 5 days a week for consecutive 4 weeks. The follow-up visit was conducted at the end of 6th week. The Pittsburg sleep quality index scale (PSQI), 17-items Hamilton depression scale (17HAMD) and Hamilton anxiety scale (HAMA) were applied for evaluation. The PSQI, HAMA and 17HAMD were observed before and after treatment; the safety was also observed.

RESULTSCompared before treatment, the PSQI was significantly decreased to (13.20±3.61) at the end of 2nd week (<0.05); compared before treatment, the 17HAMD and HAMA were significantly decreased at the end of 4th week and 6th week (all<0.05). No adverse reaction was observed.

CONCLUSIONSThe taVNS could not only relieve PI symptoms, but also improve the depressive and anxiety symptoms, in addition, it may have positive long-term efficacy and safety.

Objective To present our initial experience with modified branched stent gratis in endovacular repair of common iliac artery aneurysms.Methods In 5 patients,3 were aortobiiliac aneurysms and 2 were single common iliac aneurysms,receiving endovascular repair by a novel modified branched stent graft to keep at least one internal iliac artery patency.Results All cases were successfully completed with patent external and internal iliac artery on the target side.There were no inhospital mortality nor major complications after graft stenting.During a follow-up period of 27.6 months (21 to 33 months),there have been no stenting related endoleak and branch occlusion.Conclusions Modified branched stent graft is safe and efficient,providing an effective way to protect internal iliac artery in endovascular treatment of common iliac aneurysms.