Targeted gene sequencing reveals disparate genomic mutations between young and older adults in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is a type of cancer that can develop at any point in adulthood, spanning the range of age-related changes that occur in the body. However, the specific molecular mechanisms underlying the connections between age and genetic mutations in RCC have not been extensively investigated. METHODS: Clinical and genetic data from patients diagnosed with RCC were collected from two prominent medical centers in China as well as the TCGA dataset. The patients were categorized into two groups based on their prognosticated age: young adults (YAs) and older adults (OAs). Univariate and multivariate analysis were employed to evaluate the relationships between age and genetic mutations. Furthermore, a mediation analysis was conducted to assess the association between age and overall survival, with genetic disparities serving as a mediator. RESULTS: Our analysis revealed significant differences in clinical presentation between YAs and OAs with RCC, including histopathological types, histopathological tumor stage, and sarcomatoid differentiation. YAs were found to have lower mutation burden and significantly mutated genes (SMGs) of RCC. However, we did not observe any significant differences between the two groups in terms of 10 canonical oncogenic signaling pathways-related genes mutation, telomerase-related genes (TRGs) mutation, copy number changes, and genetic mutations associated with clinically actionable targeted drugs. Importantly, we demonstrate superior survival outcomes in YAs, and we confirmed the mediating effect of genetic disparities on these survival outcome differences between YAs and OAs. CONCLUSION: Our findings reveal previously unrecognized associations between age and the molecular underpinnings of RCC. These associations may serve as valuable insights to guide precision diagnostics and treatments for RCC.

Exploring the correlation of metabolites changes and microbial succession in solid-state fermentation of Sichuan Sun-dried vinegar.

BACKGROUND: The traditional Sichuan Sun-dried vinegar (SSV) with unique flavor and taste is believed to be generated by the solid-state fermentation craft. However, how microorganisms and their metabolites change along with fermentation has not yet been explored. RESULTS: In this study, our results demonstrated that the middle and late stages of SSV fermentation were the periods showing the largest accumulation of organic acids and amino acids. Furthermore, in the bacterial community, the highest average relative abundance was Lactobacillus (ranging from 37.55 to 92.50%) in all fermentation stages, while Acetobacters ranked second position (ranging from 20.15 to 0.55%). The number of culturable lactic acid bacteria is also increased during fermentation process (ranging from 3.93 to 8.31 CFU/g). In fungal community, Alternaria (29.42%), Issatchenkia (37.56%) and Zygosaccharomyces (69.24%) were most abundant in different fermentation stages, respectively. Interestingly, Zygosaccharomyces, Schwanniomyces and Issatchenkia were first noticed as the dominant yeast genera in vinegar fermentation process. Additionally, spearman correlation coefficients exhibited that Lactobacillus, Zygosaccharomyces and Schwanniomyces were significant correlation with most metabolites during the fermentation, implying that these microorganisms might make a significant contribution to the flavor formation of SSV. CONCLUSION: The unique flavor of SSV is mainly produced by the core microorganisms (Lactobacillus, Zygosaccharomyces and Schwanniomyces) during fermentation. This study will provide detailed information related to the structure of microorganism and correlation between changes in metabolites and microbial succession in SSV. And it will be very helpful for proposing a potential approach to monitor the traditional fermentation process.

Anti-Inflammatory and Anti-Osteoclastogenesis Activities of Different Kinds of Zanthoxylum bungeanum Seed Oil in Vitro.

Our previous study has exhibited that one kind of Zanthoxylum bungeanum seed oil (ZSO), extracted from Zanthoxylum bungeanum seed, had inhibitory effects on osteoclastogenesis. However, the anti-osteoclastogenesis activities of different kinds of ZSO are scarcely reported. Since inflammation is related to bone loss and osteoporosis, in this study, three kinds of ZSO, Zanthoxylum schinifolium Siebold et Zucc seed oil (ZSSO), Zanthoxylum armatum DC. seed oil (ZDSO) and Zanthoxylum bungeanum maximum seed oil (ZBSO), were obtained with Soxhlet extraction and their fatty acid constituents were detected by GC-FID. RAW264.7 macrophages induced by lipopolysaccharide (LPS) were used to evaluate the inhibitory effects of three kinds of ZSO on inflammation via detecting the expression levels of inflammatory factors by RT-qPCR. Moreover, RANKL-induced osteoclastogenesis was applied to demonstrate the anti-osteoclastogenesis activities of them through tartrate-resistant acid phosphatase (TRAP) staining and RT-qPCR. The GC-FID results exhibited that the highest constituent in ZSSO and ZDSO was oleic acid (OA) and palmitoleic acid (PLA), respectively. While linoleic acid (LA) and α-Linolenic acid (ALA) in ZBSO were dominant. At the concentration of 0.5 µL/mL, all three kinds of ZSO could decrease the expression levels of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß) in LPS-induced macrophages. At the concentration of 0.25 µL/mL, only ZSSO could decrease the expression levels of iNOS and COX-2, which implied the inhibitory effects of ZSSO were stronger than other ZSOs. The number of RANKL-induced osteoclasts and the expressions of nuclear factor kappa-B (NF-κB), TNF-α and IL-6 in the cells were decreased after being treated with ZSOs at the concentration of 0.5 µL/mL, while the number of RANKL-induced osteoclasts after treated with ZBSO were less than those treated with other ZSOs, this indicated that the anti-osteoclastogenesis effect of ZBSO were stronger than other ZSOs. In conclusion, the fatty acid compositions of three major kinds of ZSO were compared and the content of unsaturated fatty acids especially ω-3 polyunsaturated fatty acids in ZBSO were the highest among them. All ZSOs tested had anti-inflammatory and anti-osteoclastogenesis activities. And their anti-osteoclastogenesis effects might be related to the suppression of the NF-κB pathway.

Micropercutaneous versus Retrograde Intrarenal Surgery for the Management of Moderately Sized Kidney Stones: A Systematic Review and Meta-Analysis.

INTRODUCTION: To compare the effect of micropercutaneous surgery (microperc) and retrograde intrarenal surgery (RIRS) in the management of moderately size kidney stones. METHODS: A systematic literature search was conducted in March 2019 using PubMed, Google Scholar, Web of Science, Embase, the Cochrane Library, and Medline to identify relevant studies. A subgroup analysis was performed to compare microperc with RIRS in patients with lower-pole stones (LPS) and non-LPS (NLPS), respectively. RESULTS: Three randomized controlled trials (RCTs) and 4 non-RCTs were analyzed. Microperc provided a significantly lower rate of double-J stent insertion (p < 0.00001) but a larger decrease in hemoglobin levels (p = 0.0002). In contrast, RIRS led to a shorter hospital stay (p = 0.01) and a lower stone-free rate (SFR) (p = 0.03). IN the subgroup analysis, RIRS provided a significantly lower drop in hemoglobin drop than microperc in patients with LPSs (p = 0.0003). Microperc showed a longer operative time (p = 0.03), longer hospital stay (p = 0.04), and greater drop in hemoglobin (p = 0.04) in patients with NLPS. CONCLUSIONS: Microperc is associated with fewer double-J stent insertions and higher SFR at the expense of a greater drop in hemoglobin and longer hospital stay. Given the differences between the procedures, urologists should synthesize the individual characteristics of patients and unique advantages of these therapies so as to choose the optimal treatment for individual patients.

Non-functional paraganglioma of urinary bladder managed by transurethral resection.

PURPOSE: As a rare bladder tumor, paraganglioma of the urinary bladder (PUB) is frequently misdiagnosed as bladder cancer, particularly for the non-functional type. To date, transurethral resection remains a controversial treatment for non-functional PUB. This study aimed to identify the clinical features, pathological characteristics, prognosis, and safe/effective treatment of non-functional PUB using transurethral resection of the bladder tumor (TURBT). MATERIALS AND METHODS: The clinical records, radiological data, pathological characteristics and follow-up times were retrospectively reviewed in 10 patients with clinically and pathologically proven non-functional PUB in our hospital from January 2008 to November 2016. All patients underwent TURBT treatment. RESULTS: The incidence of non-functional PUB in patients with bladder cancer was 0.17%. The mean age at diagnosis was 44.5 ± 13.6 years (range, 29-70 years), and the patient population had a female: male ratio of 3: 2. No patients had excess catecholamine (CA) whilst four patients had painless hematuria. All neoplasms were completely resected via TURBT. The majority of samples were positive for immunohistochemical markers including chromogranin A (CgA) and Synaptophysin (Syn), but were negative for cytokeratins (CKs). Only a single recurrence was observed from the mean follow-up period of 36.4 ± 24.8 months. CONCLUSION: Complete TURBT is a safe and effi cient treatment that serves both diagnostic and therapeutic purposes. Histopathological and immunohistochemistry examinations are mandatory for diagnostic confi rmation. Long-term follow-up is recommended for patients with non-functional PUB.

[Retracted] Embelin-induced brain glioma cell apoptosis and cell cycle arrest via the mitochondrial pathway.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the flow cytometric data shown in Fig. 4A on p. 2475 were strikingly similar to data appearing in another article written by different authors at different research institutes which had already been published. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 29: 2473­2478, 2013; DOI: 10.3892/or.2013.2369].

Transmission chains and molecular characterizations of extended-spectrum ß-lactamase producing Enterobacteriaceae at a veterinary hospital in Chengdu, China.

The rapid emergence of Extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-E) is a major global public health concern. Previous studies have identified that intensive medical care of dogs and cats in veterinary hospitals have accelerated the infections and spread of ESBL-E. To investigate the spread of ESBL-E in a veterinary hospital, a total of 202 samples including hospitalized animals, veterinary healthcare workers and environment were collected from a veterinary hospital in Chengdu, China. ESBL-E were identified by antimicrobial susceptibility testing and 16 s rRNA sequencing and were further conducted on ESBL gene detection and multilocus sequence typing (MLST). At last, strains with transmission potential were analyzed by whole genome sequencing (WGS). Our results showed that the overall prevalence of ESBL-positive isolates was 34.7% (70/202), with 55.3% (26/47) in animals, 29.3% (12/41) in healthcare workers and 28.1% (32/114) in environment swabs. Twenty diverse MLST types were detected, with ST744, ST231 as the most prevalent ones. Transmission chains of two ESBL-E.coli (ST744 blaCTX-M-18, blaTEM-1) from cat_21 to cat_14, and two ESBL-Kp (ST231 blaCTX-M-27, blaTEM-1, blaSHV-1) from cat_20 to cat_37 were further confirmed by WGS. Furthermore, interdisciplinary investigation and cooperation of AMR are needed to better limit the transmissions of high-risk strains and to implement effective public health interventions.

Anisotropic SmFe10V2 Bulk Magnets with Enhanced Coercivity via Ball Milling Process.

Anisotropic bulk magnets of ThMn12-type SmFe10V2 with a high coercivity (Hc) were successfully fabricated. Powders with varying particle sizes were prepared using the ball milling process, where the particle size was controlled with milling time. A decrease in Hc occurred in the heat-treated bulk pressed from large-sized powders, while heavy oxidation excessively occurred in small powders, leading to the decomposition of the SmFe10V2 (1-12) phase. The highest Hc of 8.9 kOe was achieved with powders ball-milled for 5 h due to the formation of the grain boundary phase. To improve the maximum energy product ((BH)max), which is only 2.15 MGOe in the isotropic bulk, anisotropic bulks were prepared using the same powders. The easy alignment direction, confirmed by XRD and EBSD measurements, was <002>. Significant enhancements were observed, with saturation magnetization (Ms) increasing from 59 to 79 emu/g and a remanence ratio (Mr/Ms) of 83.7%. (BH)max reaching 7.85 MGOe. For further improvement of magnetic properties, controlling oxidation is essential to form a uniform grain boundary phase and achieve perfect alignment with small grain size.

C1QC, VSIG4, and CFD as Potential Peripheral Blood Biomarkers in Atrial Fibrillation-Related Cardioembolic Stroke.

Atrial fibrillation (AF) is a major risk factor for ischemic stroke. We aimed to identify novel potential biomarkers with diagnostic value in patients with atrial fibrillation-related cardioembolic stroke (AF-CE).Publicly available gene expression profiles related to AF, cardioembolic stroke (CE), and large artery atherosclerosis (LAA) were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified and then functionally annotated. The support vector machine recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to identify potential diagnostic AF-CE biomarkers. Furthermore, the results were validated by using external data sets, and discriminability was measured by the area under the ROC curve (AUC). In order to verify the predictive results, the blood samples of 13 healthy controls, 20 patients with CE, and 20 patients with LAA stroke were acquired for RT-qPCR, and the correlation between biomarkers and clinical features was further explored. Lastly, a nomogram and the companion website were developed to predict the CE-risk rate. Three feature genes (C1QC, VSIG4, and CFD) were selected and validated in the training and the external datasets. The qRT-PCR evaluation showed that the levels of blood biomarkers (C1QC, VSIG4, and CFD) in patients with AF-CE can be used to differentiate patients with AF-CE from normal controls (P < 0.05) and can effectively discriminate AF-CE from LAA stroke (P < 0.05). Immune cell infiltration analysis revealed that three feature genes were correlated with immune system such as neutrophils. Clinical impact curve, calibration curves, ROC, and DCAs of the nomogram indicate that the nomogram had good performance. Our findings showed that C1QC, VSIG4, and CFD can potentially serve as diagnostic blood biomarkers of AF-CE; novel nomogram and the companion website can help clinicians to identify high-risk individuals, thus helping to guide treatment decisions for stroke patients.

Molecular epidemiology and genetic diversity of canine coronavirus from domestic dogs in Chengdu, China from 2020 to 2021 using a multiplex RT-PCR.

Recent reports on identification of canine coronavirus (CCoV) in humans have emphasized the urgency to strengthen surveillance of animal CoVs. The fact that recombinations between CCoV with feline, porcine CoVs brought about new types of CoVs indicated that more attention should be paid to domestic animals like dogs, cats and pigs, and the CoVs they carried. However, there are about ten kinds of CoVs that infect above animals, and thus representative CoVs with zoonotic potentials were considered in this study. Multiplex RT-PCR against CCoV, Feline coronavirus (FCoV), porcine deltacoronavirus and porcine acute diarrhea syndrome coronavirus was developed to investigate the prevalence of CoVs from domestic dogs in Chengdu, Southwest China. Samples from a total of 117 dogs were collected from a veterinary hospital, and only CCoV (34.2%, 40/117) was detected. Therefore, this study focused on CCoV and its characteristics of S, E, M, N and ORF3abc genes. Compared with CoVs that are capable of infecting humans, CCoV strains showed highest nucleotide identity with the novel canine-feline recombinant detected from humans (CCoV-Hupn-2018). Phylogenetic analysis based on S gene, CCoV strains were not only clustered with CCoV-II strains, but also closely related to FCoV-II strains ZJU1617 and SMU-CD59/2018. As for assembled ORF3abc, E, M, N sequences, CCoV strains had the closest relationship with CCoV-II (B203_GZ_2019, B135_JS_2018 and JS2103). What's more, specific amino acid variations were found, especially in S and N proteins, and some mutations were consistent with FCoV, TGEV strains. Altogether, this study provided a novel insight into the identification, diversification and evolution of CoVs from domestic dogs. It is of top priority to recognize zoonotic potential of CoVs, and continued comprehensive surveillance will help better understand the emergence, spreading, and ecology of animal CoVs.

Microbiota and mycobiota in bronchoalveolar lavage fluid of silicosis patients.

BACKGROUND: The contribution of bronchoalveolar lavage fluid (BALF) microbiota and mycobiota to silicosis has recently been noticed. However, many confounding factors can influence the accuracy of BALF microbiota and mycobiota studies, resulting in inconsistencies in the published results. In this cross-sectional study, we systematically investigated the effects of "sampling in different rounds of BALF" on its microbiota and mycobiota. We further explored the relationship between silicosis fatigue and the microbiota and mycobiota. METHODS: After obtaining approval from the ethics board, we collected 100 BALF samples from 10 patients with silicosis. Demographic data, clinical information, and blood test results were also collected from each patient. The characteristics of the microbiota and mycobiota were defined using next-generation sequencing. However, no non-silicosis referent group was examined, which was a major limitation of this study. RESULTS: Our analysis indicated that subsampling from different rounds of BALF did not affect the alpha- and beta-diversities of microbial and fungal communities when the centrifuged BALF sediment was sufficient for DNA extraction. In contrast, fatigue status significantly influenced the beta-diversity of microbes and fungi (Principal Coordinates Analysis, P = 0.001; P = 0.002). The abundance of Vibrio alone could distinguish silicosis patients with fatigue from those without fatigue (area under the curve = 0.938, 95% confidence interval [CI] 0.870-1.000). Significant correlations were found between Vibrio and haemoglobin levels (P < 0.001, ρ = -0.64). CONCLUSIONS: Sampling in different rounds of BALF showed minimal effect on BALF microbial and fungal diversities; the first round of BALF collection was recommended for microbial and fungal analyses for convenience. In addition, Vibrio may be a potential biomarker for silicosis fatigue screening.

Prognostic factors for acute posterior circulation cerebral infarction patients after endovascular mechanical thrombectomy: A retrospective study.

ABSTRACT: This article was to analyze the factors influencing the prognosis of posterior circulation cerebral infarction (PCCI) patients, retrospectively.One hundred forty five patients diagnosed with PCCI in Nanyang Central Hospital between June 25, 2016 and October 14, 2019 were included and underwent cerebral vascular mechanical thrombectomy. The clinical data of those patients were collected. The patients were followed up for 3 months to observe the prognostic efficacy and explore the influencing factors for poor prognosis. The potential prognostic factors for PCCI patients after emergency endovascular mechanical thrombectomy were analyzed by univariate and multivariable logistic regression. The thermodynamic diagram was drawn to explore the associations between the prognostic factors.The risk of poor prognosis in PCCI patients receiving emergency endovascular mechanical thrombectomy was reduced by 0.552 time with every 1-point increase of the Alberta Stroke Program Early CT in posterior circulation score (odds ratio [OR] = 0.448, 95% confidence interval [CI]: 0.276-0.727). The risk of poor prognosis was increased by 0.827 time for each additional grade in the digital subtraction angiography-American Society of Intervention and Therapeutic Neuroradiology grading (OR = 1.827, 95% CI: 1.221-2.733, P = .003) and increased by 0.288 time for every 1-point increase in National Institutes of Health Stroke scale at 24 hours (OR = 1.288, 95% CI: 1.161-1.429). All P < .05.Alberta Stroke Program Early CT in posterior circulation score, digital subtraction angiography-American Society of Intervention and Therapeutic Neuroradiology grading, National Institutes of Health Stroke scale score at 24 hours were factors affecting the prognosis of PCCI patients undergoing emergency endovascular mechanical thrombectomy, which might provide evidence for endovascular treatment of PCCI.

Association between residential greenness and gut microbiota in Chinese adults.

BACKGROUND: A growing body of studies have reported the health benefits of greenness. However, less is known about the potential beneficial effects of residential greenness on gut microbiota, which is essential to human health. In this study, we aim to examine the association between residential greenness and gut microbiota in a population-based cohort study. METHODS: We included 1758 participants based on the China Multi-Ethnic Cohort (CMEC) study and collected their stool samples for 16S sequencing to derive gut microbiota data. Residential greenness was estimated using the satellite-based data on enhanced vegetation index (EVI) and the normalized differential vegetation index (NDVI) in circular buffers of 250 m, 500 m, and 1000 m. The relationships between residential greenness levels and the composition of gut microbiota, measured by standardized α-diversity and taxonomic composition, were assessed using linear regression and Spearman correlation weighted by generalized propensity scores. RESULTS: Higher greenness levels were significantly positively associated with standardized α-diversity. Per interquartile range (IQR) increase of EVI and NDVI in the circular buffer of 250 m were associated with the increments of 0.995(95% confidence interval (CI): 0.212-1.778) and 0.653(95% CI: 0.160-1.146) in the standardized Shannon index. For the taxonomic composition of gut microbiota, higher greenness levels were significantly correlated with 29 types of microbial taxonomic composition. NDVI in the circular buffer of 250 m was associated with increased Firmicutes (r = 0.102, adjusted p value = 0.004), which was the dominant composition in the gut microbiota. CONCLUSIONS: Increased amounts of residential greenness may support healthy gut microbiota by benignly altering their composition. These findings suggested that green spaces should be designed to support diverse gut microbiota and ultimately optimize health benefits.

Paraptosis triggers mitochondrial pathway-mediated apoptosis in Alzheimer's disease.

[This retracts the article DOI: 10.3892/etm.2015.2531.].

The visual percutaneous nephrolithotomy versus the conventional percutaneous nephrolithotomy in treatment for renal stone.

BACKGROUND: To report our initial experience using a self-made optical system to visually identify the quality of the chosen access before the operating tract dilation. METHODS: We retrospectively reviewed the data on patients with renal stones treated by percutaneous nephrolithotomy (PCNL) in our hospital. The patients were divided into Groups A and B, according to those who received treatment by visual PCNL and conventional PCNL modalities, respectively. Based on the degree of hydronephrosis, the patients in each group were further divided into two subgroups, the patients with mild hydronephrosis (subgroup 1) and the patients with moderate or severe hydronephrosis (subgroup 2). The demographics and perioperative parameters were analyzed. RESULTS: The study included 124 patients who underwent PCNL. Group A (N.=62): 47 patients were assigned to subgroup 1 and 15 to subgroup 2; group B (N.=62): 40 patients were assigned to r subgroup 1 and 22 to subgroup 2. The demographics were not significantly different between Group A and Group B (P>0.05). The puncture times were shorter in Group A and in subgroups (P<0.01), whereas the access loss rates were not significantly different (P>0.05). The mean decrease in hemoglobin levels, repuncture rates, blood transfusions and hospitalization times in Group A and Group A subgroup 1 were significantly lower than in Group B and Group B subgroup 1, respectively, (P<0.05), but no significant differences in subgroup 2 (P>0.05). When the complications were compared, the collecting system injury rates were significantly different between the two groups and in subgroup 1 (P<0.05). However the rates of fever and urinary sepsis were not statistically different in the two groups and in the subgroups (P>0.05). CONCLUSIONS: We found that visual PCNL was a safe and efficacious treatment for renal stones that may be considered as an alternative to conventional PCNL, especially in patients with mild hydronephrosis. Further prospective randomized controlled trials are needed to confirm the results of this study.

[Overexpressed miRNA-134b inhibits proliferation and invasion of CD133+ U87 glioma stem cells].

Objective To investigate the role of microRNA-134b (miR-134b) in the tumorigenesis of glioma stem cells (GSCs) and the possible molecular mechanism. Methods Real-time quantitative PCR (qRT-PCR) was used to evalate the expression of miR-134b in CD133+ and CD133- U87 GSCs. A lentiviral vector overexpressing miR-134b in U87 GSCs was constructed, and the effect of miR-134b overexpression on matrix metalloproteinase-2 (MMP-2), MMP-9 and MMP-12 expressions at both mRNA and protein levels were detected by qRT-PCR and Western blotting, respectively. TranswellTM assay was performed to determine the effect of miR-134b overexpression on GSCs invasion ability. Tumor xenograft models in nude mice were established to evaluate the effect of miR-134b overexpression on tumorgenesis in vivo. Results The qRT-PCR showed that, compared with CD133- cells, miR-134b was significantly down-regulated in CD133+ cells. Cell line over-expressing miR-134b was successfully established, and miR-134b was up-regulated significantly compared with empty vector control. Overexpression of miR-134b remarkably inhibited the invasion of U87 GSCs and the expression of MMP-12. However, overexpression of miR-134b did not affect MMP-2 and MMP-9 expressions. miR-134b also suppressed U87 GSCs xenograft growth in vivo. Tumor volume in tumor xenograft model group was significantly lower than that in control group, and tumor weight decreased by 42% in the former group. Conclusion Overexpression of miR-134b inhibits the growth and invasion of CD133+ GSCs.

[Tetramethylpyrazine attenuates experimental autoimmune myasthenia gravis in rats via regulating related cytokines and antibodies].

Objective To investigate the effects of tetramethylpyrazine (TMP) on experimental autoimmune myasthenia gravis (EAMG) in rats and explore the possible immune regulation mechanism. Methods Lewis rats were randomly divided into 4 groups: control group, EAMG group, TMP low-dose group (TMP-L, 10 mg/kg) and TMP high-dose group (TMP-H, 20 mg/kg). Except the control group, the other 3 groups were subjected to EAMG modeling. The body mass was determined and the symptoms of muscular weakness in rats were scored by Lennon EAMG criteria. The expressions of acetylcholine receptor (AChR), IgG and C3 in neuromuscular junctions were examined by immunofluorescence. The levels of R97-116 antibody (IgG1, IgG2a, IgG2b), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) and interleukin 10 (IL-10) were detected by ELISA. Results TMP decreased the scores in the evaluation of the symptoms of muscle weakness in EAMG rats. Moreover, TMP administration significantly inhibited AChR expression and increased IgG and C3 expression in neuromuscular junctions of EAMG rats. In addition, after TMP treament, the levels of IgG1, IgG2a and TNF-α were remarkably reduced, while IL-10 level was elevated. However, there was no significant change in serum levels of IgG2b and IFN-γ. Conclusion TMP can exert inhibitory effects on Th1, Th2 and B cells and modulate the levels of IgG1, IgG2a, TNF-α and IL-10. All these effects contribute to relieve the symptoms of muscle weakness in EAMG rats.

Synergistic effect of moxibustion and rehabilitation training in functional recovery of post-stroke spastic hemiplegia.

OBJECTIVE: To evaluate the therapeutic benefit of combining moxibustion and rehabilitation training for functional recovery in post-stroke spastic hemiplegic patients. METHODS: We randomly divided 84 cases subjecting to inclusion criteria into moxibustion plus rehabilitation training group (MRT group, n=44) and rehabilitation training group (RT group, n=40). Evaluation of therapeutic effect was observed before treatment, 2 weeks during treatment and 6 months after treatment. Spasticity was evaluated using modified Ashworth scale (MAS) and Clinical Spasticity Index (CSI), recovery of motor function was assessed by Brunnstrom recovery stages and Simplified Fugl-Meyer Motor Scale, and performance of activities of daily living (ADL) was measured, and the quality of life was assessed by Patient Reported Outcomes (PRO). RESULTS: Evaluation of upper limbs, hands and lower limbs based on CSI and MAS revealed significant improvements in patients treated with MRT, compared to RT alone, both during and after therapy. CSI and MAS also showed significant improvement in patients at each time point in the MRT group, compared to RT group. Marked improvement in Fugl-Meyer Motor Scale was also observed in MRT group at each time point. Based on Brunnstrom grades of upper limbs, hands and lower limbs, significant differences between the two groups were recorded at all time points during and after therapy. Barthel index (BI) and PRO also confirmed the dramatic differences between the two therapy groups. CONCLUSIONS: Our results demonstrate that combination therapy with moxibustion and rehabilitation training offers greater clinical benefits in relieving spasticity, promoting function recovery of motion, improving the performance of ADL, and increasing quality of life in post-stroke spastic hemiplegic patients, compared to RT alone.

Paraptosis triggers mitochondrial pathway-mediated apoptosis in Alzheimer's disease.

In previous years, increasing evidence has indicated that paraptosis and mitochondrial-mediated apoptosis may be associated with Alzheimer's disease (AD). However, the association between paraptosis and mitochondrial-mediated apoptosis, and the pathological processes underlying AD, remain elusive. In the present study, the ß-amyloid precursor protein gene, and the gene mutations PS1M146L and L286V, were transfected to an SH-SY5Y cell line to establish an AD cell model. Subsequently, an MTT assay was used to examine the cell viability of the AD cell model, while a TUNEL assay was employed to observe the number of positively stained apoptotic cells. Cytoplasmic vacuolization was examined using light microscopy and images were photographed. Furthermore, western blot analysis was utilized to detect the expression of golden biomarkers of the mitochondrial pathway, including Bcl-2 and Bax. The paraptosis inhibitor, cycloheximide, was selected to treat the AD model cells in order to observe the association between paraptosis and mitochondrial-mediated apoptosis. The results indicated that the decrease in the cell viability of the AD cells was initiated at 24 h, as compared with the normal cells (P<0.05). TUNEL-positive stained cells were observed at 48 h, which was later compared with the cell death initiation. In addition, examination of cytoplasmic vacuolization using microscopy indicated that there were a small number of paraptosis cells present at 24 h. The expression levels of Bcl-2 was significantly decreased, while Bax was significantly increased at 48 h. Furthermore, cycloheximide treatment was demonstrated to significantly increase Bcl-2 expression, while decreasing Bax expression (P>0.05). In conclusion, the occurrence of paraptosis was demonstrated in the early pathological stages of AD, which may subsequently damage the mitochondria and trigger mitochondrial pathway-mediated apoptosis. Thus, paraptosis may trigger programmed cell death directly, or indirectly through the regulation of Bcl-2 and Bax protein expression.

Non-functional paraganglioma of urinary bladder managed by transurethral resection

ABSTRACT Purpose As a rare bladder tumor, paraganglioma of the urinary bladder (PUB) is frequently misdiagnosed as bladder cancer, particularly for the non-functional type. To date, transurethral resection remains a controversial treatment for non-functional PUB. This study aimed to identify the clinical features, pathological characteristics, prognosis, and safe/effective treatment of non-functional PUB using transurethral resection of the bladder tumor (TURBT). Materials and Methods The clinical records, radiological data, pathological characteristics and follow-up times were retrospectively reviewed in 10 patients with clinically and pathologically proven non-functional PUB in our hospital from January 2008 to November 2016. All patients underwent TURBT treatment. Results The incidence of non-functional PUB in patients with bladder cancer was 0.17%. The mean age at diagnosis was 44.5 ± 13.6 years (range, 29-70 years), and the patient population had a female: male ratio of 3: 2. No patients had excess catecholamine (CA) whilst four patients had painless hematuria. All neoplasms were completely resected via TURBT. The majority of samples were positive for immunohistochemical markers including chromogranin A (CgA) and Synaptophysin (Syn), but were negative for cytokeratins (CKs). Only a single recurrence was observed from the mean follow-up period of 36.4 ± 24.8 months. Conclusion Complete TURBT is a safe and efficient treatment that serves both diagnostic and therapeutic purposes. Histopathological and immunohistochemistry examinations are mandatory for diagnostic confirmation. Long-term follow-up is recommended for patients with non-functional PUB.