The Intestinal Microbiota Composition in Early and Late Stages of Diabetic Kidney Disease.

Many studies have suggested that gut microbiota dysbiosis may be one of the pathogenesis factors of diabetes mellitus (DM), while it is not clear whether it is involved in the development of diabetic kidney diseases (DKD). The objective of this study was to determine bacterial taxa biomarkers during the progression of DKD by investigating bacterial compositional changes in early and late DKD. 16S rRNA gene sequencing was performed on fecal samples, including the diabetes mellitus (DM), DNa (early DKD), and DNb (late DKD) groups. Taxonomic annotation of microbial composition was performed. Samples were sequenced on the Illumina NovaSeq platform. At the genus level, we found counts of Fusobacterium, Parabacteroides, and Ruminococcus_gnavus were significantly elevated both in the DNa group (P = 0.0001, 0.0007, and 0.0174, respectively) and the DNb group (P < 0.0001, 0.0012, and 0.0003, respectively) compared with those in the DM group. Only the level of Agathobacter was significantly decreased in the DNa group than the DM group and in the DNb group than the DNa group. Counts of Prevotella_9, Roseburia were significantly decreased in the DNa group compared with those in the DM group (P = 0.001 and 0.006, respectively) and in the DNb group compared with those in the DM group (P < 0.0001 and 0.003, respectively). Levels of Agathobacter, Prevotella_9, Lachnospira, and Roseburia were positively correlated with an estimated glomerular filtration rate (eGFR), but negatively correlated with microalbuminuria (MAU), 24 h urinary protein quantity (24hUP), and serum creatinine (Scr). Moreover, the areas under the curve (AUCs) of Agathobacter and Fusobacteria were 83.33% and 80.77%, respectively, for the DM and DNa cohorts, respectively. Notably, the largest AUC for DNa and DNb cohorts was also that of Agathobacter at 83.60%. Gut microbiota dysbiosis was found in the early and late stages of DKD, especially in the early stage. Agathobacter may be the most promising intestinal bacteria biomarker that can help distinguish different stages of DKD. IMPORTANCE It is not clear as to whether gut microbiota dysbiosis is involved in the progression of DKD. This study may be the first to explore gut microbiota compositional changes in diabetes, early-DKD, and late DKD. We identify different gut microbial characteristics during different stages of DKD. Gut microbiota dysbiosis is found in the early and late stages of DKD. Agathobacter may be the most promising intestinal bacteria biomarker that can help distinguish different stages of DKD, although further studies are warranted to illustrate these mechanisms.

Solitary splenic tuberculosis: A case report.

BACKGROUND: Solitary splenic tuberculosis (TB) is unusual and rarely reported. Whether splenic TB is best treated surgically is still controversial. We describe a 73-year-old man with solitary splenic TB and no extrapulmonary TB. CASE SUMMARY: We report the case of a 73-year-old man with solitary splenic TB who complained of emaciation and fatigue. Abdominal computed tomography (CT) images suggested a splenic space-occupying lesion. We then performed a CT-guided splenic biopsy. The postoperative pathological examination revealed splenic TB. The patient took quadruple anti-TB medication. After 1 year, the patient recovered his normal weight and had no feeling of fatigue, and the splenic lesion had shrunk significantly. CONCLUSION: If patients receive combined, appropriate, regular, full-time anti-TB treatment, solitary splenic TB may be cured.

Retraction Notice to: ANXA3 Silencing Ameliorates Intracranial Aneurysm via Inhibition of the JNK Signaling Pathway.

[This retracts the article DOI: 10.1016/j.omtn.2019.06.005.].

Identification, diagnosis, and early intervention of children with developmental language disorder in Ningxia.

Background: It is reported that the incidence of language development disorder in children at the age of 2 is as high as 17.0%. Timely discovery of the high-risk factors of language development disorder in children and early intervention can greatly reduce the incidence of language development disorder and shorten the course and condition of the patients with language development disorder. Therefore, in order to facilitate prompt diagnosis and early interventions for children with language development disorder (DLD) and improve their language ability, this study explored the influence of perinatal factors on the language development of children in Ningxia and identified the unfavorable and favorable factors that influenced language development. Methods: Children diagnosed in the General Hospital of Ningxia Medical University during 2018-2021 who met the screening criteria for DLD and practical pediatric diagnostic criteria for DLD were enrolled in this study. Perinatal factors (gestational age, weight, sex, delivery mode, maternal age, presence of intrauterine infection, asphyxia) were retrospectively analyzed. The perinatal factors affecting language development were assessed using a one-way analysis of variance (ANOVA). Results: Among 1,500 children aged 0-3, 240 cases (16.00%) had language delay. Of these, 122 were male and 118 were female. There were 115 cases of comprehension and expression disorder, 30 cases of articulation disorder, and 90 cases of mixed manifestation. And there were 194 cases with definite intrauterine and perinatal high-risk factors or neonatal diseases, accounting for 80.83% of the total number of children with language delay. Conclusions: In Ningxia, factors in the neonatal period are the main cause of DLD, followed by fetal and maternal factors. Ischemic encephalopathy is the most common factor.

The Role of Circulating RBP4 in the Type 2 Diabetes Patients with Kidney Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND: Diabetic nephropathy is a common and serious complication of diabetes mellitus (DM) and is one of the leading causes of end-stage renal disease worldwide. Although there have been many investigations on biomarkers for DN, there is no consistent conclusion about reliable biomarkers. The purpose of this study was to perform a systematic review and meta-analysis of the role of circulating retinol-binding protein 4 (RBP4) in the type 2 diabetes mellitus (T2DM) patients with kidney diseases. MATERIALS AND METHODS: We searched the PubMed, MEDLINE, EMBASE, and Web of Science databases for publications. For the 12 cross-sectional studies that we included in the review, we calculated standard mean differences (SMD) with 95% confidence intervals (CI) for continuous data when the applied scales were different. Risk of bias of included trials was assessed by using the Newcastle-Ottawa Scale. RESULTS: RBP4 concentrations in the micro-, macro-, or micro+macroalbuminuria groups were significantly higher than those in the normal albuminuria group of T2DM patients [P = 0.001, SMD 1.07, 95% CI (0.41, 1.73)]. The estimated glomerular filtration rate (eGFR) was negatively associated with circulating RBP4 concentrations in patients with T2DM [summary Fisher's Z = -0.48, 95% CI (-0.69, -0.26), P < 0.0001]. The albumin-to-creatinine ratio (ACR) was positively associated with circulating RBP4 concentrations in patients with T2DM [summary Fisher's Z = 0.20, 95% CI (0.08, 0.32), P = 0.001]. CONCLUSION: The levels of circulating RBP4 were significantly higher both in T2DM subjects with micro/macroalbuminuria and in T2DM subjects with declined eGFR. The levels of circulating RBP4 were positively correlated with ACR but negatively correlated with eGFR. Circulating RBP4 could be a reliable biomarker for kidney diseases in T2DM.

Prevalence of multiple anxiety disorder and associated factors among adolescents three years after Ya’an Earthqhake / 中国学校卫生

Objective@#To examine the prevalence of multiple anxiety disorder of adolescents in Lushan, Sichuan and to provide the scientific reference for a long-term psychological intervention and rehabilitation for adolescents after earthquake.@*Methods@#In May 2016, 3 741 students were sampled in two middle schools and two high schools in Lushan county. Self-report questionnaice regarding exposure to earthquake, Screen for Child Anxiety Related Emotional Disorders (SCARED), and negative life events questionnaire (ASLES) were administered to the subjects.@*Results@#The prevalence of anxiety symptoms of adolescents in Lushan, Sichuan was 42.3%, among which panic disorder was 36.3%; generalized anxiety was 29.5%, separation anxiety was 40.3%, social anxiety was 26.1%, school fear was 32.4%. Junior school students resported more symptoms of separation anxiety than high school students (χ2=33.09, P<0.01). The results of Logistic regression showed that girls (OR=2.34, 95%CI=2.00-2.74, P<0.01), high negative life events (OR=2.87, 95%CI=2.60-3.17, P<0.01), trapped in earthqnakes (OR=1.77, 95%CI=1.18-2.67, P<0.01), parents injured (OR=1.22, 95%CI=1.03-1.43, P=0.02), experienced extreme fear (OR=1.78, 95%CI=1.52-2.08, P<0.01) were associated with higher risk of anxiety disorder.@*Conclusion@#High prevalence of anxiety disorder among adolescent following disaster need to be alerted. Adolescents among female victim or those experienced extreme fear emotion or high frequencies of negative life events, need specific intervention.

ANXA3 Silencing Ameliorates Intracranial Aneurysm via Inhibition of the JNK Signaling Pathway.

Intracranial aneurysm (IA) rupture is a major cause of stroke death. Alteration of vascular smooth muscle cell (VSMC) function and phenotypic modulation plays a role in aneurysm progression. In the present study, we investigated the role of Annexin A3 (ANXA3) silencing in IA with the interaction of the c-Jun N-terminal kinase (JNK) signaling pathway. In IA and VSMCs of IA, the relationship between ANXA3 and the JNK signaling pathway was verified. To investigate the specific mechanism of ANXA3 silencing in IA, we transfected VSMCs with the overexpressed or small interfering RNA (siRNA) of ANXA3, or treated them with an inhibitor of the JNK signaling (SP600125). Cell counting kit-8 (CCK-8) assay was conducted to detect cell viability, and flow cytometry was conducted to assess cell cycle and apoptosis so as to evaluate the gain- and loss-of-function of ANXA3 and investigate the involvement of the JNK signaling pathway. The aneurysm wall of IA cells demonstrated an elevated level of ANXA3 expression and an activated JNK signaling pathway. VSMCs treated with siRNA-ANXA3 or SP600125 showed decreased expression of JNK, caspase-3, osteopontin (OPN), Bax, and matrix metalloproteinase-9 (MMP-9), as well as phosphate (p)-JNK, but increased the expression of α smooth muscle actin (α-SMA), ß-tubulin, and Bcl-2. ANXA3 silencing or inactivation of the JNK signaling pathway also enhanced proliferation and repressed apoptosis of VSMCs. Collectively, this study shows that the silencing of ANXA3 can rescue VSMC function in IAs by inhibiting the phosphorylation and activation of the JNK signaling pathway. These findings may provide a potential therapy for the molecular treatment of IAs.

MicroRNA-143-5p targeting eEF2 gene mediates intervertebral disc degeneration through the AMPK signaling pathway.

BACKGROUND: Intervertebral disc degeneration (IDD) is a major contributor to back, neck, and radicular pain, and the treatment of IDD is costly and relatively ineffective. Dysregulation of microRNAs (miRNAs) has been reported to be involved in IDD. The purpose of our study is to illustrate the potential that miR-143-5p targeting eEF2 gene mediates IDD. METHODS: Following the establishment of the IDD rat models, expression of miR-143-5p, eEF2, Bcl-2, Bax, AMPK, mTOR, cyclinD, COL2, ACAN, and DCN was detected. The NP cells isolated from degenerative intervertebral disc (IVD) were introduced with a series of mimic, inhibitor, or AICAR to explore the functional role of miR-143-5p in IDD and to characterize the relationship between miR-143-5p and eEF2. Cell viability, cell cycle, apoptosis, and senescence were also evaluated. RESULTS: A reduction in eEF2, an increase in miR-143-5p, and activation of the AMPK signaling pathway were observed in degenerative IVD. Moreover, increased senescent NP cells were observed in degenerative IVD. eEF2 was confirmed as a target gene of miR-143-5p. miR-143-5p was found to activate the AMPK signaling pathway. The restoration of miR-143-5p or the activation of AMPK signaling pathway decreased COL2, ACAN, and DCN expression, coupled with the inhibition of NP cell proliferation and differentiation, and promotion of NP apoptosis and senescence. On the contrary, the inhibition of miR-143-5p led to the reversed results. CONCLUSION: The results demonstrated that the inhibition of miR-143-5p may act as a suppressor for the progression of IDD.

Roles of 12-Lipoxygenase and Its Interaction with Angiotensin II on p21 and p27 Expression in Diabetic Nephropathy.

BACKGROUND: 12-Lipoxygenase (12-LO) and angiotensin II (Ang II) are involved in the development of diabetic renal hypertrophy, in which cyclin-kinase inhibitors, p21 and p27 play pivotal roles. Here, we study the effects of 12-LO and its interaction with Ang II on glomerular p21 and p27 expression in diabetic conditions. METHODS: Models used in the current study include glomerular mesangial cells (MCs); and glomeruli from (1) type 2 diabetic db/db mice; (2) type 2 diabetic rats induced by high-fat diet feeding followed by streptozotocin injection; (3) 12-LO knockout (12-LOKO) mice; and (4) normal rats infused with Ang II or 12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE, arachidonic acid metabolite of 12-LO). RESULTS: The protein expression levels of p21 and p27 were increased in high glucose-stimulated MCs and in glomeruli isolated from db/db mice. In type 2 diabetic rats, cinnamyl-3,4-dihydroxy-α-cynanocinnamate (inhibitor of 12-LO) attenuated the increases in glomerular p21 and p27 protein expression, while in normal rats, 12(S)-HETE injection increased glomerular p21 and p27 expression. 12(S)-HETE and Ang II were mutually stimulated in glomeruli. Glomerular p21 and p27 expression were decreased in 12-LOKO mice compared to levels in control mice, and Ang II stimulation increased the protein expression of p27 in control but not 12-LOKO mice. Ang II stimulation had no effect on p21 protein expression in 12-LOKO mice. CONCLUSION: 12-LO is involved in diabetic renal hypertrophy via the induction of p21 and p27 protein expression and interacts with Ang II to induce p27 upregulation in diabetes. The current results suggest a potential amplifying loop in the pathogenesis of diabetic nephropathy.

Effect of oral polyethylene glycol at different time for painless colonoscopy preparation / 中国内镜杂志

Objective To compare the efficacy and comfort of oral polyethylene glycol at different time for painless colonoscopy preparation. Methods According to time of oral compound polyethylene glycol electrolyte powder, 173 painless colonoscopy patients were divided into group A, group B and group C. Patients in group A took 4 boxes of compound polyethylene glycol electrolyte powder for colonic preparation at 22:00 on day 1 before the check, the time of painless colonoscopy is 8:30 ~ 10:30. Group B patients took 1 box of compound polyethylene glycol electrolyte powder for colonic preparation at 20:00 on day 1 before the check and took 3 boxes at 5:00 am on check day, the time of painless colonoscopy is 10:30 ~ 12:30. Group C patients took 1 box of compound polyethylene glycol electrolyte powder for colonic preparation at 20:00 on day 1 before the check and took 3 boxes at 7:00 am on check day, the time of painless colonoscopy is 13:30 ~ 15:30. At last, we compare the colon cleanliness and comfort of patients among the three groups. Results There was no significant difference in instetinal cleanliness among the 3 groups (P > 0.05), but there was greatly significant difference in subjective tolerance among 3 groups (P < 0.05). Conclusion The 3 methods of having boxes of compound polyethylene glycol electrolyte power all have the satisfying effect for colonic preparation, but fractionated dose polyethylene glycol electrolyte power provides a better tolerance for bowel preparation of painless colonscopy.