OBJECTIVES: To investigate the effects of live combined Bacillus subtilis and Enterococcus faecium (LCBE) on glucose and lipid metabolism in mice with type 2 diabetes mellitus (T2DM) and circadian rhythm disorder (CRD) and explore the possible mechanisms. METHODS: KM mice were randomized into normal diet (ND) group (n=8), high-fat diet (HFD) group (n=8), and rhythm-intervention with HFD group (n=16). After 8 weeks of feeding, the mice were given an intraperitoneal injection of streptozotocin (100 mg/kg) to induce T2DM. The mice in CRD-T2DM group were further randomized into two equal groups for treatment with LCBE (225 mg/kg) or saline by gavage; the mice in ND and HFD groups also received saline gavage for 8 weeks. Blood glucose level of the mice was measured using a glucometer, and serum levels of Bmal1, PER2, insulin, C-peptide and lipids were determined with ELISA. Colon morphology and hepatic lipid metabolism of the mice were examined using HE staining and Oil Red O staining, respectively, and fecal short-chain fatty acids (SCFAs) was detected using LC-MS; GPR43 and GLP-1 expression levels were analyzed using RT-qPCR and Western blotting. RESULTS: Compared with those in CRD-T2DM group, the LCBE-treated mice exhibited significant body weight loss, lowered levels of PER2, insulin, C-peptide, total cholesterol (TC) and LDL-C, and increased levels of Bmal1 and HDL-C levels. LCBE treatment significantly increased SCFAs, upregulated GPR43 and GLP-1 expressions at both the mRNA and protein levels, and improved hepatic steatosis and colon histology. CONCLUSIONS LCBE ameliorates lipid metabolism disorder in CRD-T2DM mice by reducing body weight and improving lipid profiles and circadian regulators possibly via the SCFAs/GPR43/GLP-1 pathway.
Animals ; Mice ; Lipid Metabolism ; Diabetes Mellitus, Type 2/metabolism* ; Enterococcus faecium ; Glucagon-Like Peptide 1/metabolism* ; Bacillus subtilis ; Diabetes Mellitus, Experimental/metabolism* ; Circadian Rhythm ; Blood Glucose/metabolism* ; Receptors, G-Protein-Coupled/metabolism* ; Fatty Acids, Volatile/metabolism* ; Male ; Chronobiology Disorders/metabolism*

Objective To investigate the impact of total parathyroidectomy with autotransplantation (tPTx+AT)on bone mineral density and serum soluble Klotho (sKlotho)level in patients with secondary hyperparathyroidism (SHPT).Methods A total of 86 patients undergoing tPTx+AT in the Second Affiliated Hospital of Anhui Medical University from June 2019 to May 2022 were recruited in this study.Their demographic characteristics were collected before surgery,along with serum levels of corrected calcium,phosphorus,intact parathyroid hormone (iPTH),alkaline phosphatase (ALP),fibroblast growth factor 23 (FGF23),and sKlotho before and at 5 d,and 1,3,6,12 and 24 months after surgery.Dual energy X-ray absorptiometry was used to determine the BMD values of the lumbar spine L1-L4 before surgery and at 3,6,12 and 24 months after surgery.The changes in BMD and serum FGF23 and sKlotho levels before and after tPTx+AT were observed.Results Surgical treatment was successfully completed in all 86 patients,with their clinical symptoms such as bone pain and skin itching significantly improved postoperatively,and markedly decreased serum calcium,phosphorus,iPTH,ALP and FGF23 levels.The sKlotho level was significantly lower at 5 d postoperatively than that preoperatively,with that at 1 month after surgery increased by approximately 24.5％ than the preoperative level,and then the level was in a stable trend.The BMD values at the lumbar spine L1-L4 were increased postoperatively,and reached the highest levels at 12 months postoperatively.Further analyses showed that dialysis vintage,duration of SHPT,and ALP,iPTH and FGF23 levels were negatively correlated with the Z-scores of the lumbar spine L1-L4,while sKlotho level was positively correlated with the Z-scores.Conclusion tPTx+Atcan significantly improve the clinical symptoms of SHPT patients,regulate the balance of calcium and phosphorus metabolism,increase sKlotho level and reduce FGF23 level.It is an effective method to improve BMD.

Objective:To summarize the clinical phenotype and genetic characteristics of a case of autosomal dominant mental retardation-42 (MRD42) caused by GNB1 gene mutation. Methods:The clinical and genetic data of a case of MRD42 caused by a GNB1 gene missense mutation diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University in March 2023 were retrospectively analyzed. The child was followed-up, the child′s data were summarized, and related literature was reviewed. Results:The patient is a 6-month-old female infant, who was admitted to hospital because of "developmental delay for 3 months, intermittent convulsions for 1 month". The clinical manifestations included generalized tonic-clonic seizures, focal seizures, intellectual disability, delayed language and motor development. Long-term video electroencephalogram showed slightly slower background activity, bilateral occipital spike and wave discharges, multispike and wave complexes during sleep. Three focal onset seizures were captured. Cranial magnetic resonance imaging suggested that the subarachnoid space of the bilateral frontotemporal areas was slightly wide. Chromosome karyotype and copy number variation analysis showed no abnormality. The results of whole exon sequencing showed a de novo heterozygous missense mutation in the GNB1 gene [NM_002074:c.155(exon5)G>A;p.Arg52Gln], which had not been reported. The seizure was effectively controlled by function rehabilitation training and anti-epileptic drug therapy. Conclusions:MRD42 is a rare autosomal dominant disorder caused by mutation in the GNB1 gene. The clinical manifestations include infantile-onset seizures, mental retardation, speech and motor development delay, etc. The de novo heterozygous missense mutation in the GNB1 gene c.155G>A(p.Arg52Gln) is the genetic cause of the proband.

Objective To investigate the correlations of serum cell division cycle 42 (CDC-42), β₂-microglobulin (β₂-MG) and fibulin 1 (FBLN1) levels with abdominal aortic calcification (AAC) in patients with maintenance hemodialysis (MHD). Methods General information and biochemical indicators of 74 MHD patients were collected, and they were divided into no to mild AAC group (n=36) and moderate to severe AAC group (n=38) based on the Abdominal Aortic Calcification Score (AACs). Serum levels of CDC-42, β₂-MG and FBLN1 were compared between the two groups, and multivariate Logistic regression analysis was used to explore the risk factors for AAC in MHD patients. Results The dialysis vintage, serum phosphorus, intact parathyroid hormone (iPTH), CDC-42, β₂-MG and FBLN1 levels in the moderate to severe AAC group were significantly higher than those in the no to mild AAC group (P < 0.05). AAC in MHD patients was positively correlated with serum phosphorus, iPTH, CDC-42, β₂-MG, FBLN1, and dialysis vintage (P < 0.05). High levels of CDC-42, β₂-MG and FBLN1 as well as long dialysis vintage were independent risk factors for AAC in MHD patients (P < 0.05). Conclusion Serum CDC-42, β₂-MG and FBLN1 levels are positively correlated with AAC in MHD patients. High levels of CDC-42, β₂-MG and FBLN1 as well as long dialysis vintage are independent risk factors for AAC in MHD patients.

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 investigate the clinical characteristics and gene mutation of seven cases of CDKL5 gene related early-onset epileptic encephalopathy diagnosed by next-generation sequencing.Methods:The clinical data of children with early-onset epileptic encephalopathy from February 2018 to December 2019 in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University were retrospectively analyzed. The whole exome sequencing method was used to analyze the entire exome of the proband, and seven cases of CDKL5 gene mutation positive were screened out, and Sanger sequencing verification on family members was performed to identify the source and the characteristics of gene mutations were analyzed.Results:Among the seven children diagnosed with CDKL5 gene related early-onset epileptic encephalopathy, the ratio of male to female was 2∶5, and the age of onset was 15 days to five months of birth. The clinical phenotypes all included different degrees of developmental delay and repeated seizures, which were manifested as general seizures, myoclonic seizures, convulsive seizures or focal seizures; the outcome of use of antiepileptic drugs to control seizures was poor, and some applications of ketogenic diet had better effects. CDKL5 gene mutation sites were all denovo mutations, including NM_003159: c.772_776del (p.K258Efs *10) frameshift mutation, NM_003159.2 (exon: 9-15) heterozygous deletion, CDKL5 hemizygous deletion, NM_003159: c.268 (exon5) G>T (p.E90 *, 941) and NM_003159: c.2578C>T (p.Q860 *, 171) nonsense mutation, NM_003159: c.211A>G (p.Asn71Asp) and NM_001323289: c.545T>C (p.L182P) missense mutation. Among them, c.772_776del (p.K258Efs *10), c.268 (exon5)G>T and c.2578C>T (p.Q860 *, 171) have not been reported. Conclusions:CDKL5 gene related early-onset epileptic encephalopathy is an early onset epilepsy, which is more common in women, and has different forms of seizures. The early electroencephalogram is characterized as severe abnormal brain discharge, and the disease progresses in various forms. There are no specific changes in head magnetic resonance imaging. Different gene mutation sites may lead to different phenotypes and prognostic differences. Many anti-epileptic treatments are ineffective, and ketogenic diets are effective for some patients.

Objective: To investigate the association between mental sub-health and physical fitness of Chinese adolescents, to provide a reference for promoting the physical and mental health of Chinese adolescents. Methods: A total of 16 545 adolescents (13-22 years) were selected by random cluster sampling in six major administrative regions in China. The psychological part of the Multidimensional Sub-health Questionnaire of Adolescents (MSQA) and the physical fitness index test were used to assess mental sub-health and physical fitness, respectively. The chi-square test and Logistic regression analysis were used to analyze and compare the relationships between different levels of physical fitness and mental sub-health. Results: The overall detection rate of mental sub-health status among high-grade physical fitness index adolescents was 11.9%, and the detection rate among low-grade physical fitness index youths was 26.0%, and the difference was statistically significant (χ2=970.73，P<0.05). The overall detection rate among high-grade physical fitness index boys was 11.1%, and that of low-grade physical fitness index boys was 24.4%. The difference was statistically significant (χ2=566.12，P<0.05). The overall detection rate of mental sub-health status among high-level physical fitness index girls was 12.8%, and that among low-level physical fitness index girls was 27.6%, and the difference was statistically significant (χ2=412.25，P<0.05). After adjusting for gender, age, BMI, and region in the Logistic regression model, the detection rate of mental sub-health status of adolescents with low-grade physical fitness index was 2.35 times higher than that of high-grade physical fitness index adolescents(95%CI=2.12-2.61). Conclusion Adolescents with poor physical fitness have a higher risk of mental sub-health.Attention should be paid to adolescent physical fitness development to comprehensively improve physical and mental health development.

Objective:To investigate the CT and MRI features of sinonasal lymphoepithelial carcinoma (LEC) and to compare functional MRI index of LEC with olfactory neuroblastoma (ONB) in this area.Methods:The clinical data, CT and MRI conventional findings of 7 patients were retrospectively reviewed . All of the patients, 5 males and 2 females, with age of 35-58 (45±9) years old, were histologically diagnosed as LEC of sinonasal tract at Beijing Tongren Hospital, Capital Medical University from February 2014 to November 2019. The semi-quantitative DCE-MRI parameters and ADC value were measured and compared with 18 cases of ONB which were collected during the same period. Independent sample t test or corrected t test, Fisher′s exact test were performed to compare the differences between the two groups. Results:In all of the 7 LEC patients, 6 lesions were located in naso-ethmoid area, 1 lesion was located in naso-orbital area. Six lesions were on the left side, and another one was sitted on both sides. All tumors manifested irregular soft tissue density with bony destruction, 3 of them showed bony sclerosis. All lesions showed homogeneous density or signal and obvious enhancement in solid portion accompanied with varying degrees of local invasion. Morphologically, two forms were observed: localized soft tissue mass and diffuse infiltration along mucosa. There were polypoid strips ( n=3), spherical masses ( n=3), and diffuse thickening of nasal cavity and turbinate mucosa ( n=1). DCE-MRI examinations were performed in six LEC patients. Maximum contrast enhancement index (CI max) was 1.51±0.46, wash out ratio (WR) was 14.26%±6.24%. Time intensity curve (TIC) showed a plateau pattern (type Ⅱ) in 4 cases and a washout pattern (type Ⅲ) in 2 cases. Time to peak (T peak) were (40.09±4.59)s, showing a rapid peak performance. Diffusion weighted imaging was performed in six LEC patients, and the ADC value was (0.80±0.14)×10 -3 mm 2/s. There were statistical differences in WR and ADC values between sinonasal LEC and ONB ( t=4.873, P=0.020 and t=3.255, P=0.025). Conclusion:The radiological manifestations of LEC have certain characteristics. The characteristics of conventional imaging findings and functional MRI index combined with clinical data are helpful in making differential diagnosis between LEC and other sinonasal malignant tumors.

Objective:To explore the relationship between respiratory mechanics and right heart function during ARDS mechanical ventilation through the establishment of Beagle dogs acute respiratory distress syndrome (ARDS) animal model and the application of different levels of mechanical ventilation, which will provide theoretical basis for right heart protective ventilation strategy of ARDS.Methods:Beagle dogs were anesthetized successfully and then pulmonary artery floating catheter, esophageal manometric catheter and femoral artery catheter were inserted. Under the pressure control mode, the driving pressure was fixed. After adjustment, PEEP gradually increased from 2 cmH 2O to 14 cmH 2O. The changes of respiratory mechanics, hemodynamics and right heart function were observed. ARDS model was established by injecting oleic acid into central vein, and mechanical ventilation with the same parameters was given after the model was established successfully. In contrast to itself, the changes of respiratory mechanics, hemodynamics and right heart function indexes of experimental dogs before and after modeling were analyzed. In the group, the indexes of different PEEP were compared by ANOVA, and then compared by Student-Newman-Keuls. The difference was statistically significant at a P value <0.05. Results:Before modeling, the peak airway pressure (P peak) and plateau pressure (P plat) increased with the increase of PEEP ( F=232.733,196.33, P<0.05). However, P trans-I, P trans-E, C stat and Vt decreased significantly ( F=4.524, 6.499, 64.803, 2.31, P<0.05). The area of change of right ventricle (FAC) became smaller ( F=3.09, P<0.05); SV first increased and then decreased ( F=3.24, P<0.05), and CVP and MPAP increased ( F=19.07,14.81, P<0.05). There was no significant difference in TAPSE, MAP, HR and SpO 2 ( P>0.05). After modeling, as PEEP increased, P peak, P plat, P ES-I and P ES-E increased significantly ( F=24.829, 41.95, 9.78, 87.86, P<0.05). Vt, P trans-I, P trans-E, C stat and Vt first increased and then decreased ( F=2.91, 4.29, 5.84, 48.890, P<0.05). TAPSE and SV first increased and then decreased ( F=6.22,6.54, P<0.05). CVP and MPAP increased ( F=5.23, 19.24, P<0.05). MAP increased first and then decreased ( F=5.02, P<0.05). SpO 2 increased ( F=2.77, P<0.05). FAC and HR had no statistical significance ( P>0.05). Conclusions:Trans pulmonary pressure and lung compliance can reflect the effectiveness of ARDS lung recruitment, and have good synergy; with the increase of PEEP, the right ventricular systolic function TAPSE is first affected, and SV compensatory increase, but with the increase of PEEP, TAPSE and SV decrease; pulmonary blood flow distribution is more important in improving alveolar oxygenation. Therefore, real-time monitoring of trans pulmonary pressure, TAPSE and intrapulmonary blood flow should be performed in ARDS treatment.