Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to address this gap.ICGN was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered orally.Two and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were conducted.Fecal microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal function.Approximately 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both stages.Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was reduced.Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces.FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal function.These findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its pro-gression.MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.

Alzheimer′s disease (AD) is a neurodegenerative disorder. In the past few decades, the exact mechanisms underlying the onset of the disease have remained unclear, and treatment options are still lacking. Due to the inability of two-dimensional cell and animal models to fully simulate the pathogenesis of AD, there have been shortcomings in clinical trials of new drugs. The development of organoids and organ-on-a-chip technologies has improved the dilemma of AD research, providing reliable in vitro research models for studying pathogenic mechanisms and drug screening. This article elaborates on the applications and progress of organoids and organ-on-a-chip in AD modeling, pathogenesis, and drug development, and discusses the current limitations of organoids and organ-on-a-chip and their future perspectives.

Microcephaly is a common pediatric neurodevelopmental disorder with complex etiology. In recent years, with the development of brain organoid technology, there has been rapid progress in understanding the pathogenesis and treatment strategies of microcephaly using this technology. This article elucidates the advantages of brain organoids over traditional experimental models, reviews the research progress of brain organoid technology in disease modeling and drug screening for various causes of microcephaly, and discusses the limitations and future prospects of brain organoids.

Objective:To investigate the expression of soluble T cell immunoglobulin and mucin domain-3 (Tim-3) in peripheral blood of patients with pancreatic cancer and its diagnostic value in combination with serum Carbohydrate antigen 19-9 (CA19-9) .Methods:106 newly diagnosed pancreatic cancer patients and 65 age and sex matched healthy individuals were enrolled. Tim-3 concentration was quantitatively determined by enzyme-linked immunosorbent assay (ELISA). According to the expression levels of soluble Tim-3 and serum CA19-9, a binary logistic regression model of receiver operating characteristic (ROC) curve was established to compare the diagnostic effects of serum CA19-9 and soluble Tim-3 alone or combined with the two tests.Results:The levels of soluble Tim-3 in the pancreatic cancer group were significantly higher than those in the healthy control group ( P<0.001). The expression level of soluble Tim-3 was significantly higher in patients with stage III-IV pancreatic cancer than in patients with stage I-II ( P=0.003). The AUC of soluble Tim-3 diagnosis for stage I-II pancreatic cancer was 0.856 (95%CI: 0.765 to 0.992 P<0.001), Serum CA19-9 The AUC used for the stage I-II pancreatic cancer diagnosis was 0.862 (95%CI: 0.772 to 0.926 P<0.001), The AUC for the combined diagnosis was 0.949 (95%CI: 0.880 - 0.985 P<0.001) ; In a healthy population and in patients with stage III-IV pancreatic cancer, the AUC of soluble T I I-IV pancreatic cancer in stage III was 0.927 (95%CI: 0.873 to 0.963 P<0.001), the AUC of serum CA19-9 used for the diagnosis of stage III-IV pancreatic cancer was 0.933 (95%CI: 0.881 to 0.968 P<0.001), the AUC for the combined diagnosis was 0.989 (95%CI: 0.956 to 0.999 P<0.001) . Conclusions:The combination of soluble Tim-3 and serum CA19-9 can improve the diagnostic rate of pancreatic cancer patients.

Objective:To compare the efficacy and safety of Changsulin ? with Lantus ? in treating patients with type 2 diabetes mellitus (T2DM). Methods:This was a phase Ⅲ, multicenter, randomized, open-label, parallel-group, active-controlled clinical trial. A total of 578 participants with T2DM inadequately controlled on oral hypoglycemic agents were randomized 3∶1 to Changsulin ? or Lantus ? treatment for 24 weeks. The efficacy measures included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2h postprandial plasma glucose (2hPG), 8-point self-monitoring of blood glucose (SMBG) profiles from baseline, and proportions of subjects achieving targets of HbA1c and FPG. The safety outcomes included rates of hypoglycemia, adverse events (AEs) and anti-insulin glargine antibody. Results:After 24 weeks of treatment, mean HbAlc decreased 1.16% and 1.25%, FPG decreased 3.05 mmol/L and 2.90 mmol/L, 2hPG decreased 2.49 mmol/L and 2.38 mmol/L in Changsulin ? and in Lantus ?, respectively. No significant differences could be viewed in above parameters between the two groups (all P>0.05). There were also no significant differences between Changsulin ? and Lantus ? in 8-point SMBG profiles from baseline and proportions of subjects achieving the targets of HbA1c and FPG (all P>0.05). The rates of total hypoglycemia (38.00% and 39.01% for Changsulin ? and Lantus ?, respectively) and nocturnal hypoglycemia (17.25% and 16.31% for Changsulin ? and Lantus ?, respectively) were similar between the two groups (all P>0.05). Most of the hypoglycemia events were asymptomatic, and no severe hypoglycemia were found in both groups. No differences were observed in rates of AEs (61.77% vs.52.48%) and anti-insulin glargine antibody (after 24 weeks of treatment, 6.91% vs.3.65%) between the two groups (all P>0.05). Conclusions:Changsulin ? shows similar efficacy and safety profiles compared with Lantus ? and Changsulin ? treatment was well tolerated in patients with T2DM.

Objective:To investigate the effect of Chinese reading aloud training (c-RAT) on cognitive function and activities of daily living in patients with vascular cognitive impairment no dementia (VCIND).Methods:From January 2018 to January 2019, totally 80 patients with VCIND in the General Hospital of Xingtai Mining Group were enrolled.Subjects were randomized grouped into c-RAT group ( n=43) and control group ( n=37). The c-RAT group was asked to read aloud the Chinese paper for 5 days a week for 12 weeks.At the time of enrollment and 12 weeks after the intervention, the Montreal cognitive assessment (MoCA), trail making test (TMT), auditory verb learn test (AVLT), digit symbol substitution test (DSST) and modified Barthel index (MBI) were filled out. Results:Compared with control group, the difference of D-value in c-RAT group was statistically significant in MoCA total scores(4.00(2.00), 1.50(0.50), Z=3.012, P=0.003), scores of MoCA-Visual space execution (2.00(1.00), 0.00(2.00), Z=2.787, P=0.008), MoCA-attention (1.00(1.00), 0.00(0.50), Z=2.369, P=0.022), MoCA-language (1.00(1.00), 0.00(0.75), Z=3.049, P=0.000)and MoCA-delayed recall(2.00(2.00), 0.00(1.00), Z=2.043, P=0.014), TMT-A scores (-8.00(23.00), 10.50(30.25), Z=2.120, P=0.039), AVLT scores (1earning)(3.00(2.00), 0.50(0.75), Z=2.266, P=0.039) , AVLT scores (recall)(2.00(1.00), 0.00(1.00), Z=2.974, P=0.003)、AVLT scores (recognition) (2.00(0.00), 0.50(1.50), Z=3.054, P=0.000)and DSST scores ((4.96±0.71), (2.39±0.78), t=2.572, P=0.014), while there were no significant differences in the rest parts of MoCA, TMT-B and MBI( P>0.05). The increased scores in DSST were positively correlated ( r=0.205, P=0.006) with the number of reading aloud tasks finished. Conclusion:C-RAT can improve general cognition, especially in information processing speed, executive function, attention and auditory memory.

Nasal high flow oxygen therapy (HFNC), an open nasal catheter system conveying heated and humidified air or oxygen, has been used to treat hypoxemic respiratory failure. At present, some researches indicated that HFNC can be applied for chronic obstructive pulmonary disease (COPD) with hypercapnia, which attenuates the retention of carbon dioxide by positive end-expiratory pressure effect, washing out anatomical dead space and reducing work of breath. HFNC is proved to decrease respiratory frequency, increase alveolar ventilation and end-expiratory lung volume, and its therapeutic effect is similar to non-invasive ventilation. Application of HFNC managed to be optimized in a way of increasing the flow rate in a single prong and mouth-closed breathing. This article summarizes the application of HFNC in COPD with hypercapnia.

Objective: To analyze and compare the changes of cardiac structure and function in patients with borderline pulmonary hypertension. Methods: Echocardiographic data of 617 outpatients from February to October 2018 in Peking University People′s Hospital were retrospectively analyzed. According to the estimated mean pulmonary artery pressure (mPAP), the patients were divided into normal group (mPAP<19 mmHg), borderline group (19 mmHg≤mPAP<25 mmHg) and elevated group (mPAP≥25 mmHg). Results: ①Compared with normal group，the patients were older in borderline group and elevated group[(39.2±10.1)years old vs (46.5±13.5)years old vs (51.8±14.2)years old，all P<0.001] and the proportions of male were relatively lower (69.9% vs 58.9% vs 54.4%，all P<0.01). The incidences of smoking，drinking and cardiovascular complications increased significantly. ②Compared with normal group，the left atrium[(30.2±8.2)ml/m² vs (34.5±9.7)ml/m²，P<0.001]，left ventricle[(57.4±11.6)ml/m² vs (60.6±12.5)ml/m²，P<0.01]and right atrium[(19.5±5.9)ml/m² vs (22.6±7.0)ml/m²，P<0.001] were enlarged in borderline group.Left ventricular global long-axis strain (GLS_LV) increased[(-20.1±2.5)% vs (-21.1±3.1)%，P<0.001]，but the long-axis strain in the middle segment of right ventricular free wall (GLS_RVFWmid) decreased[(-31.4±6.6)%对(-27.2±8.8)%，P<0.001] in borderline group.Meanwhile，left ventricular diastolic function was impaired. ③Age，sex，right atrial volume，right ventricular area，RV-S′，GLS_LV，GLS_RVFWmid and mitral valve E/e′ were independent risk factors for mPAP elevation. Conclusions Early changes of cardiac structure and function exist in the patients with borderline pulmonary hypertension. Echocardiography is critical for the early diagnosis and follow-up monitoring of pulmonary hypertension.

Objective: To examine the Quality of life among school-aged children with dyslexia in target city and to provide scientific evidence for improving the quality of life of children with dyslexia. Methods: By using cluster sampling,students from grade 3 to grade 6 from 6 primary schools in a middle-sized were selected and administered with questionnaire survey. According to the criteria of dyslexia, dyslexic children and non-dyslexic children were identified and the difference of the Quality of Life was compared. Results: Totally 3 673 children were collected, and 119 of them were identified as dyslexia(3.24%).The prevalence of dyslexia differed by gender,grades,educational level of parents(χ2=24.77,11.75,18.50,9.79,P<0.05). The Quality of Life which below the average proportion accounted for 30.3% of dyslexic children and 16.7% of normal children. Quality of life scored signiticantly different between dyslexic children and non-dyslexia children, including psychosocial functioning domain(134.54±30.88)(143.49±32.53), physical and mental health domain(2.71±0.84)(2.92±0.81) vs (2.83±0.90)(3.06±0.87), the living satisfaction domain(2.95±0.87)(3.14±0.87)(t=-6.09，-5.48，-5.44，-4.50，P<0.01),with dyslexic group significantly lower than that of non-dyslexic group. Conclusion The Quality of Life of Dyslexic children was in a poor condition.

Objective To analyze and compare the classification of left atrial size by different echocardiographic measurements based on the latest large sample of normal Chinese adults'echocardiographic data . Methods The echocardiography data of 1067 unselected adult outpatients were retrospectively analyzed . The outpatients were divided into normal or enlarged groups according to the left atrialantero-posteriordiameter(LAD)andleftatrialvolume(LAV),respectively.Results ①LADand LAV enlargement were found in 299 (28 .0％ ) patients and 449 (42 .1％ ) patients of the total population , respectively . ②There was a good positive linear correlation between LAD and LAV ( r = 0 .642 , P =0 .000) ,but the agreement for the classification of left atrial size by LAD and LAV was not ideal ( Kappa =0 .392 , P = 0 .000) . The majority of the patients ( 74 .6％ ) with abnormal LAD had abnormal LAV . Conversely ,among the patients with abnormal LAV ( 50 .3％ ) had normal LAD . ③ The sensitivity and specificity of judging left atrial enlargement were 76 .8％ and 66 .8％ for LAD>3 .7 cm in male ,and 74 .9％and 70 .6％ for LAD>3 .4 cm in female ,respectively . The sensitivity and specificity of judging severely left atrial enlargement were 75 .5％ and 78 .7％ for LAD>4 .0 cm in male ,and 84 .2％ and 75 .8％ for LAD>3 .7 cm in female ,respectively . Conclusions The agreement of the classification of left atrial size by LAD and LAV is limited . LAD-based assessment may result in an underestimation of left atrial size . When LAD is larger than 4 .0 cm for male or 3 .7 cm for female ,the accuracy of LAD in the diagnosis of left atrial enlargement is better .