Microvesicles from Mesenchymal Stem Cells Overexpressing MiR-34a Ameliorate Renal Fibrosis In Vivo.

INTRODUCTION: We recently discovered that microvesicles (MVs)  derived from mesenchymal stem cells (MSCs) overexpressing  miRNA-34a can alleviate experimental kidney injury in mice. In  this study, we further explored the effects of miR34a-MV on renal  fibrosis in the unilateral ureteral obstruction (UUO) models.  Methods. Bone marrow MSCs were modified by lentiviruses  overexpressing miR-34a, and MVs were collected from the  supernatants of MSCs. C57BL6/J mice were divided into control,  unilateral ureteral obstruction (UUO), UUO + MV, UUO + miR-34aMV and UUO + miR-34a-inhibitor-MV groups. MVs were injected  to mice after surgery. The mice were then euthanized on day 7  and 14 of modeling, and renal tissues were collected for further  analyses by Hematoxylin and eosin, Masson's trichrome,  and Immunohistochemical (IHC) staining.  Results. The UUO + MV group exhibited a significantly reduced  degree of renal interstitial fibrosis with inflammatory cell infiltration,  tubular epithelial cell atrophy, and vacuole degeneration compared  with the UUO group. Surprisingly, overexpressing miR-34a enhanced  these effects of MSC-MV on the UUO mice.  Conclusion. Our study demonstrates that miR34a further enhances  the effects of MSC-MV on renal fibrosis in mice through the  regulation of epithelial-to-mesenchymal transition (EMT) and  Notch pathway. miR-34a may be a candidate molecular therapeutic  target for the treatment of renal fibrosis. DOI: 10.52547/ijkd.7673.

A new active bone-conduction implant: surgical experiences and audiological outcomes in patients with bilateral congenital microtia.

PURPOSE: First-generation bone bridges (BBs) have demonstrated favorable safety and audiological benefits in patients with conductive hearing loss. However, studies on the effects of second-generation BBs are limited, especially among children. In this study, we aimed to explore the surgical and audiological effects of second-generation BBs in patients with bilateral congenital microtia. METHODS: This single-center prospective study included nine Mandarin-speaking patients with bilateral microtia. All the patients underwent BCI Generation 602 (BCI602; MED-EL, Innsbruck, Austria) implant surgery between September 2021 and June 2023. Audiological and sound localization tests were performed under unaided and BB-aided conditions. RESULTS: The transmastoid and retrosigmoid sinus approaches were implemented in three and six patients, respectively. No patient underwent preoperative planning, lifts were unnecessary, and no sigmoid sinus or dural compression occurred. The mean function gain at 0.5-4.0 kHz was 28.06 ± 4.55-dB HL. The word recognition scores improved significantly in quiet under the BB aided condition. Signal-to-noise ratio reduction by 10.56 ± 2.30 dB improved the speech reception threshold in noise. Patients fitted with a unilateral BB demonstrated inferior sound source localization after the initial activation. CONCLUSIONS: Second-generation BBs are safe and effective for patients with bilateral congenital microtia and may be suitable for children with mastoid hypoplasia without preoperative three-dimensional reconstruction.

A 3-Year Follow-Up and Radiological Analysis of Cochlear Implantation Patients with Cochlear Nerve Deficiency and Modiolar Deficiency-Type Malformations.

OBJECTIVE: Cochlear nerve deficiency (CND) is often combined with modiolar deficiency-type inner ear malformations, which cause variable cochlear implantation (CI) outcomes. We aimed to assess the postoperative development of auditory and speech perception in CND patients with modiolar deficiency-type malformations after 3 years of follow-up to determine the factors correlated with CI outcomes. METHODS: Sixty-seven CND patients with modiolar deficiency-type malformations who underwent CI surgery were retrospectively reviewed. Modiolar deficiency-type malformations included common cavity (CC), cochlear hypoplasia (CH) (including CH-I and CH-II) and incomplete partition-I (IP-I). Categorical auditory performance (CAP) and the infant-toddler meaningful auditory integration scale (MAIS) were used to assess auditory ability. The speech intelligibility rating (SIR) and meaningful use of speech scale (MUSS) were used to assess the speech intelligibility of these CI patients. The CI outcomes were evaluated at 0, 12, 24 and 36 months after implant activation. RESULTS: All patients demonstrated improvements in auditory ability and speech intelligibility after CI. There were no significant differences in CI outcomes at any time point according to the malformation type. The number of nerve bundles within the internal auditory canal (IAC) showed significant differences at 12, 24 and 36 months after CI ( p < 0.05). Patients with one nerve bundle had relatively poor CI outcomes. CONCLUSIONS: CND patients with modiolar deficiency-type malformations showed continuous improvement in auditory and speech abilities after CI. Compared with malformations, the number of nerve bundles should be given more attention when selecting the side for CI.

Berberine ameliorates pulmonary inflammation in mice with influenza viral pneumonia by inhibiting NLRP3 inflammasome activation and gasdermin D-mediated pyroptosis.

Viral pneumonia is a common complication caused by Influenza A virus infection and is characterized by severe pulmonary inflammation. A previous study showed that berberine (BBR) significantly ameliorated the pulmonary inflammation in mice with influenza viral pneumonia but its underlying mechanism is not entirely understood. In this study, we reproduced the mouse model of influenza viral pneumonia through intranasal infection of A/Puerto Rico/8/34 (H1N1), to further investigate the anti-inflammatory mechanism of BBR based on nucleotide-binding oligomerization domain-like receptor protein (NLRP) 3 inflammasome activation and Gasdermin D (GSDMD)-mediated pyroptosis. Consistent with MCC950 (10 mg/kg, a specific NLRP3 inflammasome inhibitor), BBR (10 mg/kg) obviously improved the weight loss and survival rate of infected mice, alleviated their pulmonary inflammation, and suppressed the accumulation of tumor necrosis factor and interleukin (IL)-6 in lungs without obvious inhibition on viral multiplication (hemagglutinin titer and nucleoprotein messenger RNA). Moreover, BBR (10 mg/kg) reduced the expressions of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and cysteinyl aspartate-specific proteinase (Caspase)1 (Caspase1 precursor [Pro-caspase1] + Caspase1p20 subunit) and the ratio of Caspase1p20 subunit to Caspase1, thus inhibiting the NLRP3 inflammasome activation and resulting in the decreased contents of mature IL-1ß and IL-18 in lungs. The GSDMD expression (GSDMD precursor [Pro-GSDMD] + GSDMD-N terminal [NT]) and the ratio of GSDMD-NT to GSDMD were also declined by BBR (10 mg/kg). These evidence indicate that BBR may ameliorate pulmonary inflammation in mice with influenza viral pneumonia through inhibiting NLRP3 inflammasome activation, as well as depressing GSDMD-mediated pyroptosis via declining GSDMD expression and restraining NLRP3 inflammasome-mediated GSDMD activation.

Expansion of Escherichia-Shigella in Gut Is Associated with the Onset and Response to Immunosuppressive Therapy of IgA Nephropathy.

BACKGROUND: Gut dysbiosis is postulated to participate in the pathogenesis of IgA nephropathy (IgAN). However, the key bacterial taxa closely associated with IgAN onset and treatment response have not been identified. METHODS: We recruited 127 patients with IgAN who were treatment naive and 127 matched healthy controls (HCs) who were randomly divided into discovery and validation cohorts to investigate the characteristics of their gut microbiota and establish a bacterial diagnosis model for IgAN. A separate cohort of 56 patients and HCs was investigated to assess crossregional validation. A further 40 patients with primary membranous nephropathy (MN) were enrolled to probe disease-specific validation. A subgroup of 77 patients was prospectively followed to further dissect the association between alterations in gut microbiota and treatment response after 6 months of immunosuppressive therapy. Fecal microbiota samples were collected from all participants and analyzed using 16S ribosomal RNA sequencing. RESULTS: Decreased α-diversity (Shannon, P=0.03), altered microbial composition (Adonis, P=0.0001), and a striking expansion of the taxonomic chain Proteobacteria-Gammaproteobacteria-Enterobacteriales-Enterobacteriaceae-Escherichia-Shigella (all P<0.001) were observed in patients with IgAN who were treatment naive, which reversed only in patients who achieved clinical remission after 6 months of immunosuppressive therapy. Importantly, seven operational taxa units, of which Escherichia-Shigella contributed the most, were determined to be the optimal bacterial classifier of IgAN (AUC=0.8635, 0.8551, 0.8026 in discovery, validation, and cross-regional validation sets, respectively), but did not effectively distinguish patients with IgAN versus those with MN (AUC=0.6183). Bacterial function prediction further verified enrichment of the shigellosis infection pathway in IgAN. CONCLUSION: Gut dysbiosis, characterized by a striking expansion of genus Escherichia-Shigella, is a hallmark of patients with IgAN and may serve as a promising diagnostic biomarker and therapeutic target for IgAN. Further studies are warranted to investigate the potential contribution of Escherichia-Shigella in IgAN pathogenesis.

Machine Learning-Based Prediction of the Outcomes of Cochlear Implantation in Patients With Cochlear Nerve Deficiency and Normal Cochlea: A 2-Year Follow-Up of 70 Children.

Cochlear nerve deficiency (CND) is often associated with variable outcomes of cochlear implantation (CI). We assessed previous investigations aiming to identify the main factors that determine CI outcomes, which would enable us to develop predictive models. Seventy patients with CND and normal cochlea who underwent CI surgery were retrospectively examined. First, using a data-driven approach, we collected demographic information, radiographic measurements, audiological findings, and audition and speech assessments. Next, CI outcomes were evaluated based on the scores obtained after 2 years of CI from the Categories of Auditory Performance index, Speech Intelligibility Rating, Infant/Toddler Meaningful Auditory Integration Scale or Meaningful Auditory Integration Scale, and Meaningful Use of Speech Scale. Then, we measured and averaged the audiological and radiographic characteristics of the patients to form feature vectors, adopting a multivariate feature selection method, called stability selection, to select the features that were consistent within a certain range of model parameters. Stability selection analysis identified two out of six characteristics, namely the vestibulocochlear nerve (VCN) area and the number of nerve bundles, which played an important role in predicting the hearing and speech rehabilitation results of CND patients. Finally, we used a parameter-optimized support vector machine (SVM) as a classifier to study the postoperative hearing and speech rehabilitation of the patients. For hearing rehabilitation, the accuracy rate was 71% for both the SVM classification and the area under the curve (AUC), whereas for speech rehabilitation, the accuracy rate for SVM classification and AUC was 93% and 94%, respectively. Our results identified that a greater number of nerve bundles and a larger VCN area were associated with better CI outcomes. The number of nerve bundles and VCN area can predict CI outcomes in patients with CND. These findings can help surgeons in selecting the side for CI and provide reasonable expectations for the outcomes of CI surgery.

Cochlear implantation for post-meningitis deafness with cochlear ossification: diagnosis and surgical strategy.

BACKGROUND: Cochlear ossification (CO) after meningitis can cause profound sensorineural hearing loss (SNHL). Cochlear implantation (CI) is the ideal treatment strategy for CO. AIMS: To explore the strategy for CI in patients with CO after meningitis. MATERIALS AND METHODS: In this retrospective study, the medical records of patients diagnosed with profound SNHL due to CO after meningitis and who underwent CI in our department between September 2010 and September 2021 were collected and reviewed. Their imaging and surgical findings were analyzed. RESULTS: The data of 26 patients with unilateral CI were reviewed. All patients underwent preoperative temporal high-resolution computed tomography (HRCT) and 22 patients magnetic resonance imaging (MRI). The sensitivity of HRCT was 61.5% (10/26), whereas that of MRI was 81.8% (18/22). Combined HRCT and MRI achieved a detection rate of 92.3% (24/26). Twenty-two and four patients underwent complete and partial electrode implantations, respectively. CONCLUSIONS AND SIGNIFICANCE: Preoperative temporal bone HRCT and MRI are essential for determining whether a patient is suitable for CI and surgical planning. A false-negative diagnosis is possible when diagnosing CO, but combined HRCT and MRI can improve the positive rate of preoperative diagnosis of CO post meningitis. Early CI is recommended.

Imbalance of alveolar epithelial type I and type â ¡ cells in lipopolysaccharide-induced chronic lung injury young mouse model.

Children are susceptible to pneumonia, which affects their growth and development. Immune disorders and unrepaired alveolar mucosal epithelium following pneumonia cause chronic lung injury. The mechanism of chronic lung injury is unknown and lacks animal models for reference. Therefore, we developed a chronic lung injury young mouse model to simulate the pathological process of children. 3-week-old mice were intratracheal instillation of lipopolysaccharide (LPS) every other day for six weeks. Consequently, the histopathology showed damaged integrity of lung tissue, fibrosis, and abnormally distributed alveolar epithelial cells. The total protein concentration in bronchoalveolar lavage fluid (BALF) was increased, alveolar epithelial type (AT) I cells were abnormal distribution, and AT II cells were reduced. The phosphorylation levels of IKBα and the expression levels of NF-κB p65 in lung tissue were up-regulated. In serum and BALF, the IL-6 was oversecretion, nitric oxide (NO) and superoxide dismutase (SOD) were perturbed secretion, oxidative stress imbalance. In addition, blood viscosity, plasma viscosity, and erythrocyte sedimentation rate (ESR) indexes in hemorheology were increased. In conclusion, it is feasible to construct the mouse model of chronic lung injury, and AT I and AT Ⅱ cells were imbalanced, which paves the way for further investigations on the pathogenesis of chronic lung injury and the efficacy of novel treatments.

[Sagittaria sagittifolia polysaccharides regulates Nrf2/HO-1 to relieve liver injury caused by multiple heavy metals in vivo and in vitro].

This study explored whether Sagittaria sagittifolia polysaccharides(SSP) activates the nuclear factor erythroid-2-related factor2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway to protect against liver damage jointly induced by multiple heavy metals. First, based on the proportion of dietary intake of six heavy metals in rice available in Beijing market, a heavy metal mixture was prepared for inducing mouse liver injury and HepG2 cell injury. Forty male Kunming mice were divided into five groups: control group, model group, glutathione positive control group, and low-and high-dose SSP groups, with eight mice in each group. After 30 days of intragastric administration, the liver injury in mice was observed by HE staining. In the in vitro experiment, MTT assay was conducted to detect the effects of SSP at 0.25, 0.5, 1, and 2 mg·mL~(-1) on HepG2 cell survival at different time points. The content of alanine transaminase(ALT) and aspartate aminotransferase(AST) in the 48-h cell culture fluid was measured using micro-plate cultivation method, followed by the detection of the change in reactive oxygen species(ROS) content by flow cytometry. The mRNA expression levels of Nrf2 and HO-1 in cells were determined by RT-PCR, and their protein expression by Western blot. HE staining results showed that compared with the model group, the SSP administration groups exhibited significantly alleviated inflammatory cell infiltration and fatty infiltration in the liver, with better outcomes observed in the high-dose SSP group. In the in vitro MTT assay, compared with the model group, SSP at four concentrations all significantly increased the cell survival rate, decreased the ALT, AST, and ROS content(P<0.05), and down-regulated Nrf2 and HO-1 mRNA and protein expression(P<0.05). SSP significantly improves inflammatory infiltration in the liver tissue of mice exposed to a variety of heavy metals and corrects the liver fat degeneration, which may be related to its regulation of the Nrf2/HO-1 signaling pathway, reduction of ROS, and alleviation of oxidative damage.

Gegen Qinlian Decoction Alleviates Experimental Colitis and Concurrent Lung Inflammation by Inhibiting the Recruitment of Inflammatory Myeloid Cells and Restoring Microbial Balance.

OBJECTIVE: Ulcerative colitis (UC) as one of the intractable diseases in gastroenterology seriously threatens human health. Respiratory pathology is a representative extraintestinal manifestation of UC affecting the quality of life of patients. Gegen Qinlian Decoction (GQD) is a classical traditional Chinese medicine prescription for UC or acute lung injury. This study was aimed to reveal the therapeutic effect of GQD on UC and its pulmonary complications and uncover its molecular mechanism mediated by myeloid cells and microbiota. METHODS: Mice with DSS-induced colitis were orally administrated with GQD. Overall vital signs were assessed by body weight loss and disease activity index (DAI). Pulmonary general signs were evaluated by pulmonary pathology and lung function. The mechanism of GQD relieving UC was characterized by detecting myeloid cells (neutrophils, macrophages, inflammatory monocytes, and resident monocytes) in colonic and lung tissues, related inflammatory cytokines, as well as the microbiota in bronchoalveolar lavage fluid (BALF) and feces. RESULTS: GQD significantly reduced weight loss, DAI scores, and lung injury but improved the lung function of colitis mice. The DSS-induced colonic and concurrent pulmonary inflammation were also alleviated by GQD, as indicated by the down-regulated expressions of inflammatory cytokines (TNF-α, IL-1ß, IL-6, CCR2, and CCL2) and the suppressed recruitment of neutrophils and inflammatory monocytes. Meanwhile, GQD greatly improved intestinal microbiota imbalance by enriching Ruminococcaceae UCG-013 while decreasing Parabacteroides, [Eubacterium]_fissicatena_group, and Akkermansia in the feces of colitis mice. Expectantly, GQD also restored lung microbiota imbalance by clearing excessive Coprococcus 2 and Ochrobactrum in the BALF of colitis mice. Finally, significant correlations appeared between GQD-mediated specific bacteria and inflammatory cytokines or immune cells. CONCLUSION: GQD could alleviate UC by decreasing excessive inflammatory myeloid cells and cytokines, and reshaping the microbiota between the colon and lung, which contributes to clarifying the mechanism by which GQD ameliorates colitis-associated pulmonary inflammation.

Xuanbai Chengqi Decoction Ameliorates Pulmonary Inflammation via Reshaping Gut Microbiota and Rectifying Th17/Treg Imbalance in a Murine Model of Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic obstructive pulmonary disease (COPD), a prevalent obstructive airway disease, has become the third most common cause of death globally. Xuanbai Chengqi decoction (XBCQ) is a traditional Chinese medicine prescription for the acute exacerbation of COPD. Here, we aimed to reveal the therapeutic effects of XBCQ administration and its molecular mechanisms mediated by Th17/Treg balance and gut microbiota. METHODS: We determined the counts of Th17 and Treg cells in the serum of 15 COPD and 10 healthy subjects. Then, cigarette smoke extract-induced COPD mice were gavaged with low, middle, and high doses of XBCQ, respectively. Weight loss, pulmonary function and inflammation, Th17/Treg ratio, and gut microbiota were measured to evaluate the efficacy of XBCQ on COPD. RESULTS: COPD patients had a higher Th17/Treg ratio in the serum than healthy controls, which was consistent with the results in the lung and colon of COPD mice. The middle dose of XBCQ (M-XBCQ) significantly decreased the weight loss and improved the pulmonary function (FEV0.2/FVC) in COPD mice. Moreover, M-XBCQ alleviated lung inflammation by rectifying the Th17/Treg imbalance, reducing the expressions of TNF-α, IL-1ß, and MMP-9, and suppressing inflammatory cells infiltration. Meanwhile, M-XBCQ greatly improved the microbial homeostasis in COPD mice by accumulating probiotic Gordonibacter and Akkermansia but inhibiting the growth of pathogenic Streptococcus, which showed significant correlations with pulmonary injury. CONCLUSION: Oral M-XBCQ could alleviate COPD exacerbations by reshaping the gut microbiota and improving the Th17/Treg balance, which aids in elucidating the mechanism through which XBCQ as a therapy for COPD.

The prognostic effect of immunosuppressive therapy in IgA nephropathy with stage 3 or 4 chronic kidney disease.

BACKGROUND: It is debated whether patients with IgAN with heavy proteinuria and decreased eGFR benefit from aggressive treatment consisting of corticosteroids alone or combined with immunosuppressive agents. METHODS: A retrospective study was performed between January 2008 and December 2016 on patients with IgAN who had urinary protein excretion > 1.0 g/d and an eGFR between 15 and 59 mL/min/1.73 m2. These patients were assigned to receive supportive care alone or supportive care plus immunosuppressive therapy. The primary outcome was defined as the first occurrence of a 50% decrease in eGFR or the development of ESKD. RESULTS: All 208 included patients were followed for a median of 43 months, and 92 (44%) patients experienced the primary outcome. Cumulative kidney survival was better in the immunosuppression group than in the supportive care group (p < .001). The median annual rate of eGFR decline in the immunosuppression group was -2.0 (-7.3 to 4.2), compared with -8.4 (-18.9 to -4.1) mL/min/1.73 m2 in the supportive care group (p < .001). In multivariate Cox regression analyses, immunosuppressive therapy was associated with a lower risk of progression to ESKD, independent of age, sex, eGFR, proteinuria, MAP, kidney histologic findings and the use of RASi agents (HR = 0.335; 95% CI 0.209-0.601). Among the adverse events, infection requiring hospitalization occurred at similar rates in both groups (p = .471). CONCLUSION: Immunosuppressive therapy attenuated the rate of eGFR decline and was associated with a favorable kidney outcome in IgAN patients with heavy proteinuria and decreased eGFR, and the side effects were tolerable.

Comparison of gefitinib-induced skin adverse reactions (SAR) in C57BL/6 and FVB/N mice.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib, erlotinib, and afatinib, are widely used in clinical practice and remarkably effective in treatment of advanced non-small cell lung cancer. However, there are some adverse effects while taking EGFR-TKIs, among which skin adverse reactions (SAR) are the most common events. At present, the poor outcome of SAR and insufficient research on SAR models need to be addressed. In this study we focused on the SAR models to lay a foundation for mechanism researches. Gefitinib, one of the EGFR-TKIs, was used as SAR inducing agents. We chose C57BL/6 and FVB/N mice as experimental model and they were divided into four groups. The weight and skin moisture of mice were detected every 7 days, itching behavior and abnormal eyelids were tested at 35th day after gavage, and survival rate was also recorded. The weight of unit area hair, length of whiskers and inflammatory cells were evaluated after mice sacrificed. C57BL/6 animals treated with gefitinib showed significant differences in survival rate, weight of unit area hair, skin moisture changes, skin dryness, itching behavior, whisker irregular growth, abnormal eyelids, and inflammatory cells; FVB/N animals treated with gefitinib only showed significant differences in survival rate, whisker irregular growth and abnormal eyelids, compared with the control group, respectively. In this study, we compared the similarities and differences of gefitinib-induced SAR between C57BL/6 and FVB/N mice, which illustrated different patients probably showing different symptoms clinically and provided experimental basis for researching mechanism of EGFR-TKIs induced SAR.

Effects of Wireless Remote Microphone on Speech Recognition in Noise for Hearing Aid Users in China.

Objective: This study was aimed at evaluating improvements in speech-in-noise recognition ability as measured by signal-to-noise ratio (SNR) with the use of wireless remote microphone technology. These microphones transmit digital signals via radio frequency directly to hearing aids and may be a valuable assistive listening device for the hearing-impaired population of Mandarin speakers in China. Methods: Twenty-three adults (aged 19-80 years old) and fourteen children (aged 8-17 years old) with bilateral sensorineural hearing loss were recruited. The Mandarin Hearing in Noise Test was used to test speech recognition ability in adult subjects, and the Mandarin Hearing in Noise Test for Children was used for children. The subjects' perceived SNR was measured using sentence recognition ability at three different listening distances of 1.5, 3, and 6 m. At each distance, SNR was obtained under three device settings: hearing aid microphone alone, wireless remote microphone alone, and hearing aid microphone and wireless remote microphone simultaneously. Results: At each test distance, for both adult and pediatric groups, speech-in-noise recognition thresholds were significantly lower with the use of the wireless remote microphone in comparison with the hearing aid microphones alone (P < 0.05), indicating better SNR performance with the wireless remote microphone. Moreover, when the wireless remote microphone was used, test distance had no effect on speech-in-noise recognition for either adults or children. Conclusion: Wireless remote microphone technology can significantly improve speech recognition performance in challenging listening environments for Mandarin speaking hearing aid users in China.

Specific alterations in gut microbiota in patients with chronic kidney disease: an updated systematic review.

BACKGROUND: Emerging evidence demonstrates that gut dysbiosis is implicated in the pathogenesis of chronic kidney disease (CKD) with underlying mechanisms involving mucosal and/or systematic immunity or metabolic disorders. However, the profile of gut microbiota in patients with CKD has not been completely explored. METHODS: Databases from their date of inception to 31 March 2020 were systematically searched for case-control or cross-sectional studies comparing the gut microbial profiles in adult patients with CKD or end-stage renal disease (ESRD) with those in healthy controls. Quantitative analysis of alterations in gut microbial profiles was conducted. RESULTS: Twenty-five studies with a total of 1436 CKD patients and 918 healthy controls were included. The present study supports the increased abundance of, phylum Proteobacteria and Fusobacteria, genus Escherichia_Shigella, Desulfovibrio, and Streptococcus, while lower abundance of genus Roseburia, Faecalibacterium, Pyramidobacter, Prevotellaceae_UCG-001, and Prevotella_9 in patients with CKD; and increased abundance of phylum Proteobacteria, and genus Streptococcus and Fusobacterium, while lower abundance of Prevotella, Coprococcus, Megamonas, and Faecalibacterium in patients with ESRD. Moreover, higher concentrations of trimethylamine-N-oxide and p-cresyl sulfate and lower concentrations of short-chain fatty acids were observed. Gut permeability in patients with CKD was not determined due to the heterogeneity of selected parameters. CONCLUSIONS: Specific alterations of gut microbial parameters in patients with CKD were identified. However, a full picture of the gut microbiota could not be drawn from the data due to the differences in methodology, and qualitative and incomplete reporting of different studies.

Effect of electroacupuncture on glial fibrillary acidic protein and nerve growth factor in the hippocampus of rats with hyperlipidemia and middle cerebral artery thrombus.

Electroacupuncture (EA) has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia. However, there are few studies on the results and mechanism of the effect of EA in reducing blood lipid level or promoting neural repair after stroke in hyperlipidemic subjects. In this study, EA was applied to a rat model of hyperlipidemia and middle cerebral artery thrombosis and the condition of neurons and astrocytes after hippocampal injury was assessed. Except for the normal group, rats in other groups were fed a high-fat diet throughout the whole experiment. Hyperlipidemia models were established in rats fed a high-fat diet for 6 weeks. Middle cerebral artery thrombus models were induced by pasting 50% FeCl3 filter paper on the left middle cerebral artery for 20 minutes on day 50 as the model group. EA1 group rats received EA at bilateral ST40 (Fenglong) for 7 days before the thrombosis. Rats in the EA1 and EA2 groups received EA at GV20 (Baihui) and bilateral ST40 for 14 days after model establishment. Neuronal health was assessed by hematoxylin-eosin staining in the brain. Hyperlipidemia was assessed by biochemical methods that measured total cholesterol, triglyceride, low-density lipoprotein and high-density lipoprotein in blood sera. Behavioral analysis was used to confirm the establishment of the model. Immunohistochemical methods were used to detect the expression of glial fibrillary acidic protein and nerve growth factor in the hippocampal CA1 region. The results demonstrated that, compared with the model group, blood lipid levels significantly decreased, glial fibrillary acidic protein immunoreactivity was significantly weakened and nerve growth factor immunoreactivity was significantly enhanced in the EA1 and EA2 groups. The repair effect was superior in the EA1 group than in the EA2 group. These findings confirm that EA can reduce blood lipid, inhibit glial fibrillary acidic protein expression and promote nerve growth factor expression in the hippocampal CA1 region after hyperlipidemia and middle cerebral artery thrombosis. All experimental procedures and protocols were approved by the Animal Use and Management Committee of Beijing University of Chinese Medicine, China (approval No. BUCM-3-2018022802-1002) on April 12, 2018.

Learning a Second Language in Adulthood Changes Subcortical Neural Encoding.

Second language learning has been shown to impact and reshape the central nervous system, anatomically and functionally. Most of the studies on second language learning and neuroplasticity have been focused on cortical areas, whereas the subcortical neural encoding mechanism and its relationship with L2 learning have not been examined extensively. The purpose of this study was to utilize frequency-following response (FFR) to examine if and how learning a tonal language in adulthood changes the subcortical neural encoding in hearing adults. Three groups of subjects were recruited: native speakers of Mandarin Chinese (native speakers (NS)), learners of the language (L2 learners), and those with no experience (native speakers of foreign languages (NSFL)). It is hypothesized that differences would exist in FFRs obtained from the three language experience groups. Results revealed that FFRs obtained from L2 learners were found to be more robust than the NSFL group, yet not on a par with the NS group. Such results may suggest that in human adulthood, subcortical neural encoding ability may be trainable with the acquisition of a new language and that neuroplasticity at the brainstem level can indeed be influenced by L2 learning.

A Comparative Study of the Gut Microbiota Associated With Immunoglobulin a Nephropathy and Membranous Nephropathy.

The pathogenesis of immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) is characterized by immune dysregulation, which is related to gut dysbiosis. The aim of the study was to compare the gut microbiota of patients with IgAN and MN vs. healthy controls. We used 16S rDNA amplicon sequencing to investigate the bacterial communities of 44 patients with kidney biopsy-proven IgAN, 40 patients with kidney biopsy-proven MN, and 30 matched healthy controls (HC). The abundance of Escherichia-Shigella and Defluviitaleaceae_incertae_sedis were significantly higher in IgAN than in HC, whereas lower abundances were observed for Roseburia, Lachnospiraceae_unclassified, Clostridium_sensu_stricto_1, and Fusobacterium. Furthermore, the abundance of Escherichia-Shigella, Peptostreptococcaceae_incertae_sedis, Streptococcus, and Enterobacteriaceae_unclassified increased, while that of Lachnospira, Lachnospiraceae_unclassified, Clostridium_sensu_stricto_1, and Veillonella decreased in MN. The abundance of Megasphaera and Bilophila was higher, whereas that of Megamonas, Veillonella, Klebsiella, and Streptococcus was lower in patients with IgAN than in those with MN. Analysis of the correlations showed that in the IgAN group, Prevotella was positively correlated, while Klebsiella, Citrobacter, and Fusobacterium were negatively correlated with the level of serum albumin. Positive correlation also existed between Bilophila and Crescents in the Oxford classification of IgAN. In the MN group, negative correlation was observed between Escherichia-Shigella and proteinuria, Bacteroides and Klebsiella showed positive correlation with the MN stage. Patients with IgAN and MN exhibited gut microbial signatures distinct from healthy controls. Our study suggests the potential of gut microbiota as specific biomarker and contributor in the pathogenesis of IgAN and MN.

[Analysis of hearing screening results in adult health check-up population].

Objective:To obtain incidence of hearing loss and the influence factors in adult health check-up population, and to provide supporting information for the prevention of hearing loss. Method:Hearing Handicap Inventory for the Adult-screening（HHIA-S）, electro-otoscopy and pure tone test were used to evaluate subjects'hearing health condition. SPSS 25.0 software was used to perform one-way ANOVA on the results. Result:①HHIA-S questionnaire results: 3704 subjects completed the questionnaire, 29 subjects（0.8%） were reported hearing difficulties in daily life. ②Hearing screening results: 1264 subjects failed to pass the hearing screening, including 936 male and 328 female subjects. 33.5% subjects with noramlself-rated hearing failed to pass the hearing screening test, and all the patients with abnormal self-rated hearing did not pass the hearing screening.③The passing rate of hearing screening was significantly affected by gender, age, BMI, blood pressure and plasma glucose. The passing rate of hearing screening was higher in female than that in male, in younger than that in elder, in subjects with normal blood pressure, plasma glucose and BMI than those with abnormal above conditions. Conclusion:Aging, abnormal blood pressure, fasting plasma glucose and BMI may have potential risks on hearing health. Therefore, it is of practical significance to carry out hearing screening in adult population. For those adults with abnormal indexes, they should pay close attention to their hearing condition status and monitor their hearing regularly.

Sagittaria sagittifolia polysaccharide interferes with arachidonic acid metabolism in non-alcoholic fatty liver disease mice via Nrf2/HO-1 signaling pathway.

BACKGROUNDS: Non-alcoholic fatty liver disease (NAFLD) is currently one of the most common chronic liver diseases especially in developed countries. Modern research shows an obvious protective effect of Sagittaria sagittifolia L. (Alismataceae) on glucose and lipid metabolism disorders. Previous studies had reported that Sagittaria sagittifolia polysaccharide (SSP) has potent protective effects on drug-induced liver injury. Based on this, we speculated that Sagittaria sagittifolia polysaccharide also has protective effects on NAFLD and performed experiments to explore this more. METHODS: Outstanding protective effects of SSP against NAFLD in mice was observed with Hematoxylin and Eosin (H&E) and uranium acetate-citrate stain in our prophase research. By performing bioinformatics analysis on plasma metabolic data which is obtained from ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS), we found the regulatory mechanisms and key nodes behind the beneficial effect with IPA (Ingenuity Pathway Analysis) software. Immunohistochemical staining and Western blot were performed for further validation on expression variations of key proteins. RESULTS: Regulatory pathways were enriched with 33 significant differential metabolites that responded to SSP treatment in plasma, and specifically, the ones related to arachidonic acid metabolism showed high participation. Moreover, the expression patterns of upstream regulators, Nrf2 and HO-1, were found to be significantly regulated upon SSP treatment. CONCLUSIONS: In conclusion, our findings illustrated a novel perspective that SSP exerts preventive protection against high-fat diet-induced NAFLD by interfering with arachidonic acid metabolism via Nrf2/HO-1 signaling pathway in liver oxidative stress, providing an attractive point for the breakthrough of related natural medicine development.