Regulating effect of miR-132-3p on the changes of MAPK pathway in rat brains and SH-SY5Y cells exposed to excessive fluoride by targeting expression of MAPK1.

BACKGROUND: Although the changes of mitogen-activated protein kinase (MAPK) pathway in the central nervous system (CNS) induced by excessive fluoride has been confirmed by our previous findings, the underlying mechanism(s) of the action remains unclear. Here, we investigate the possibility that microRNAs (miRNAs) are involved in the aspect. METHODS: As a model of chronic fluorosis, SD rats received different concentrations of fluoride in their drinking water for 3 or 6 months and SH-SY5Y cells were exposed to fluoride. Literature reviews and bioinformatics analyses were used to predict and real-time PCR to measure the expression of 12 miRNAs; an algorithm-based approach was applied to identify multiply potential target-genes and pathways; the dual-luciferase reporter system to detect the association of miR-132-3p with MAPK1; and fluorescence in situ hybridization to detect miR-132-3p localization. The miR-132-3p inhibitor or mimics or MAPK1 silencing RNA were transfected into cultured cells. Expression of protein components of the MAPK pathway was assessed by immunofluorescence or Western blotting. RESULTS: In the rat hippocampus exposed with high fluoride, ten miRNAs were down-regulated and two up-regulated. Among these, miR-132-3p expression was down-regulated to the greatest extent and MAPK1 level (selected from the 220 genes predicted) was corelated with the alteration of miR-132-3p. Furthermore, miR-132-3p level was declined, whereas the protein levels MAPK pathway components were increased in the rat brains and SH-SY5Y cells exposed to high fluoride. MiR-132-3p up-regulated MAPK1 by binding directly to its 3'-untranslated region. Obviously, miR-132-3p mimics or MAPK1 silencing RNA attenuated the elevated expressions of the proteins components of the MAPK pathway induced by fluorosis in SH-SY5Y cells, whereas an inhibitor of miR-132-3p just played the opposite effect. CONCLUSION: MiR-132-3p appears to modulate the changes of MAPK signaling pathway in the CNS associated with chronic fluorosis.

Rare papillary renal neoplasm with reverse polarity: A case report and review of the literature.

Papillary renal neoplasm with reverse polarity (PRNRP) is a rare renal tumour and was newly named in 2019. This study reported a case of a 30-year-old female patient with a left renal tumour without any clinical symptoms and whose CT scan of her left kidney showed a mass of 2.6 cm×2.3 cm, which was considered to be renal clear cell carcinoma. Laparoscopic partial nephrectomy was performed, and histopathology and immunohistochemistry confirmed papillary renal neoplasm with reverse polarity, which had unique clinicopathological features, immunophenotype, KRAS gene mutation and relatively indolent biological behaviour. As newly diagnosed cases, rigorous and regular follow-up is necessary. In addition, a literature review was performed from 1978 to 2022, and 97 cases of papillary renal neoplasms with reverse polarity were identified and analysed.

Variation in quality of care by medical institute level in China: a systematic review protocol.

INTRODUCTION: Quality variation has been widely witnessed and discussed in China. However, limited evidence reveals quality gaps by the medical institute level, especially between hospitals and primary care institutes. This systematic review will synthesise the available evidence on quality variation between medical institutes at different levels in China. By adopting a quality framework, we will also explore the detailed domains (structure, process and outcomes) and dimensions (safety, effectiveness, timeliness, patient-centredness, efficiency, integration and equity) of quality gaps. METHODS AND ANALYSIS: An extensive literature search will be conducted on eight key electronic databases: MEDLINE, Web of Science, Cochrane Library, Scopus, EMBASE, ProQuest, China National Knowledge Infrastructure and WANFANG database. The Grey Matter Checklist will be used to screen relevant grey literature. The publication time limit should be before 31 December 2022 when we plan to conduct a literature search. All kinds of studies that revealed the quality difference between medical institutes at different levels will be included, no matter if quality improvement intervention is involved. All quality measures and indicators will be recorded and sorted into appropriate domains and dimensions. For those studies that took the completion rate of standard operations to assess the quality, we will also record the name of the clinical pathways, guidelines or checklists used. Two reviewers will independently perform the study selection, data extraction and quality assessment process. A narrative or quantitative synthesis will be performed based on the available data. ETHICS AND DISSEMINATION: Ethics approval is not applicable. The results of this study will be submitted to a widely accepted peer-review journal. The findings will also be used to inform administration about quality gaps by different medical institute levels and, therefore, help them to design policies that will minimise the quality variation. PROSPERO REGISTRATION NUMBER: CRD42022345933.

Tunable Photochromism of Spirooxazine in the Solid State: A New Design Strategy Based on the Hypochromic Effect.

As an important organic photofunctional material, spirooxazine (SO) usually does not exhibit photochromism in the solid state since the intermolecular π-π stacking impedes photoisomerization. Developing photochromic SO in the solid state is crucial for practical applications but is still full of challenges. Here, a series of spirooxazine derivatives (SO1-SO4) with bulky aromatic substituents at the 4- and 7-positions of the skeleton, which provide them with a large volume with which to undergo solid-state photochromism under mild conditions, is designed and synthesized. All the compounds SO1-SO4 exhibit tunable solid photochromism without ground colors, excellent fatigue resistance, and high thermal stability. Notably, it takes only 15 s for SO4 to reach the saturation of absorption intensity, thought to represent the fastest solid-state photoresponse of spirooxazines. X-ray crystal structures of the intermediate compound SO0 and the products SO1-SO2 as well as computational studies suggest that the bulky aromatic groups can lead to a hypochromic effect, allowing for the photochromism of SO in the solid state. The ideal photochromic properties of these spirooxazines open a new avenue for their applications in UV printing, quick response code, and related fields.

Clinical practice of rapid antigen tests for SARS-CoV-2 Omicron variant: A single-center study in China.

Responding to the fast-spreading SARS-CoV-2 Omicron variant, to improve screening efficiency, rapid antigen tests (RATs) were first added as a supplementary detection method in China in mid-March, 2022. What and how big a role RATs should play need to be supported by clinical data. Here, RAT performance and relevant factors in comparison with nucleic acid amplification tests (NAATs) were assessed in Omicron-infected inpatients. From the NAAT results, nasopharyngeal swabs (NPs) performed better than oropharyngeal swabs (OPs). RATs tested on NAAT positive NPs performed better than those with OP-positive samples. The RAT positivity rate was strongly associated with high levels of N and OFR1ab genes, especially in NPs where patients also had significantly longer hospital stays and shorter days from symptom onset to RAT testing. Self-performed RATs had a detection accuracy that was comparable to professionally performed RATs when the subjects were well guided. The antigen negative rate of the studied patients was 100% at discharge. These findings suggest that, in addition to a supplementary detection role, RATs can be an important strategy for evaluating the disease progression of Omicron-infected inpatients. This study provides important clinical data to support better rules regarding RATs under China's COVID-19 prevention and control policy.

Quality of Care in Public County Hospitals: A Cross-Sectional Study for Stroke, Pneumonia, and Heart Failure Care in Eastern China.

There are very few studies about the quality of care (QoC) in Chinese county hospitals. Using 7, 6, and 6 standard operations from clinical pathways as the process indicators, we evaluated the quality of stroke, pneumonia, and heart failure care, respectively. We also conducted chi-squared tests to detect differences of quality between selected counties or hospitals. We extracted relevant information from medical records of 421 stroke cases, 329 pneumonia cases, and 341 heart failure cases, which were sampled from 6 county hospitals in 3 counties of eastern China. The average proportion of recommended care delivered included stroke, pneumonia, and heart failure patients at 55.36%, 41.64%, and 49.56%, respectively. Great variation of QoC was detected not only across selected counties but between comprehensive county hospitals and traditional Chinese medicine county hospitals. We deny the widely-accepted assumptions that poor QoC should be blamed on defectively-equipped facilities or medicine and overwhelmed care providers. Instead, we speculate the low qualifications of medical workers, failed clinical knowledge translation, incorrect diagnosis, and a lack of electronic systems could be the reasons behind poor QoC. It is high time for China to put QoC as the national health priority.

Rare primary bladder mucosa-associated lymphoid tissue lymphoma: A case report and review of literature.

Primary bladder mucosa-associated lymphoid tissue (MALT) lymphoma is an extremely rare bladder tumor. Only scarce reports have been reported. We hereby report a case of an 81-year-old female patient with bladder tumor presenting with frequent urination and dysuria, whose pelvic magnetic resonance imaging (MRI) considered bladder cancer. She underwent transurethral resection of the bladder tumor (TURBT), and histopathology confirmed the mass to be bladder MALT lymphoma. The patient refused further treatment, and no disease recurrence one year after surgery. The current data are insufficient to draw conclusions about the long-term efficacy of treatment for this tumor, regular follow-up is necessary. To further understand the clinical features, pathology, treatment and prognosis of this tumor, we have searched the literature from 1990 to the present, analyzing a total of 64 cases of primary MALT lymphoma.

Variant-Specific Adsorption, Desorption, and Dissipation of Microcystin Toxins in Surface Soil.

Microcystins (MCs) are hepatotoxic heptapeptides identified in cyanobacterial bloom-impacted waters and soils. However, their environmental fate in soils is poorly understood, preventing reliable site assessment. This study aims to clarify the variant-specific adsorption, desorption, and dissipation of MC-LR and MC-RR in agricultural soils. Results revealed that their adsorption isotherms followed the Freundlich model (R2 ≥ 0.96), exhibiting a higher nonlinear trend and lower adsorption capacity for MC-LR than for MC-RR. The soils had low desorption rates of 8.14-21.06% and 3.06-34.04%, respectively, following a 24 h desorption cycle. Pairwise comparison indicated that soil pH and clay played key roles in MC-LR adsorption and desorption, while organic matter and cation exchange capacity played key roles in those of MC-RR. MC-LR dissipation half-lives in soils were 27.18-42.52 days, compared with 35.19-43.87 days for MC-RR. Specifically, an appreciable decrease in MC concentration in sterile soils suggested the significant role of abiotic degradation. This study demonstrates that the minor structural changes in MCs might have major effects on their environmental fates in agricultural soil and indicates that the toxic effects of MCs should be of high concern due to high adsorption, low desorption, and slow dissipation.

Incidental diagnosis of nonfunctional bladder paraganglioma: a case report and literature review.

BACKGROUND: Nonfunctional bladder paragangliomas is a rare urological disease. It may present clinical, radiology and pathological features similar to bladder cancer, Only scarce reports have been reported. Urologist must identify this generally benign neuroendocrine neoplasm to avoid misdiagnosis. CASE PRESENTATION: A 62-year-old female presented the outpatient department of our hospital with the symptoms of stomachache, frequent micturition, and urination pain for 20 days. Diagnosed with high blood pressure 1 year ago, administered Amlodipine besylate tablets 5 mg po qd occasionally, did not check blood pressure; denied any tumor observation in the family history. Color ultrasound of the urinary system showed a 38 mm × 34 mm hypoechoic mass on the right side of the bladder, CDFI: in the masses, blood supply was sufficient. Cystoscope showed bladder occupying lesion. Biopsy diagnosis: papillary polypoid cystitis was suspected as a malignant change (Fig. 3a). Then, the patient was admitted to our urological department. Further, computer tomography urography considered bladder cancer. Cystoscopy and biopsy failed to define the nature of the lesions in our outpatient department, which prompted a transurethral resection of the bladder tumor. histopathological and immunohistochemical results were diagnosed as bladder paragangliomas. For the reason, the tumor was removed by partial resection of the bladder. The postoperative recovery and follow-up were uneventful. CONCLUSIONS: Nonfunctional bladder paragangliomas are occasionally found on imaging studies with the symptoms of urinary tract infection or/and intermittent painless hematuria. It may present clinical, radiology and pathological features similar to bladder cancer, so knowledge of this generally benign neuroendocrine neoplasm is of great importance to avoid misdiagnosis. It should be accompanied by the clinical and pathological characteristics of the patient and image changes. Partial resection of the bladder can effectively treat this disease.

Mycobacterial identification on homogenised biopsy facilitates the early diagnosis and treatment of laryngeal tuberculosis.

INTRODUCTION: The incidence of laryngeal tuberculosis has increased gradually in recent years. Laryngeal tuberculosis has strong infectivity and atypical clinical manifestations. Hence, establishing the early diagnosis of laryngeal tuberculosis is considered difficult, resulting in the high rate of misdiagnosis of laryngeal tuberculosis and increased rates of tuberculosis infection. OBJECTIVE: This study aimed to describe a case of laryngeal tuberculosis detected using the mycobacteria gene chips technology, facilitating the early diagnosis and the treatment of laryngeal tuberculosis. CASE PRESENTATION: A 27-year-old woman presented with a 7-day history of hoarseness, with a normal routine blood chemistry test and chest computed tomography results. Histological analysis of the vocal cord biopsy showed granulomatous inflammation and the negative acid-fast stain test. The mycobacteria gene chips method was used to directly examine the vocal cord tissue treated with homogenate, and the Mycobacterium tuberculosis was successfully identified. Thus, the early diagnosis of laryngeal tuberculosis and the drug sensitivity of rifampin and isoniazid were confirmed. The patient recovered after undergoing a 1-year standard anti-tuberculosis therapy. CONCLUSIONS: Mycobacterial identification on homogenised biopsy using the mycobacteria gene chips method significantly facilitates the early diagnosis and the treatment of tuberculosis.

Bladder Outlet Obstruction Induced by the Compression of Displaced Hemipelvic Prosthesis After Pelvic Reconstruction: A Case Report.

Bladder outlet obstruction (BOO) is a common urological condition usually caused by benign prostatic hyperplasia, prostate cancer, urethral stricture, rarely by compression of surrounding organs. Herein we presented a BOO patient caused by the compression of displaced hemipelvic prosthesis after pelvic reconstruction. This report may help to increase awareness of BOO as a late complication of pelvic reconstruction.

Prediction of competing endogenous RNA coexpression network as prognostic markers in AML.

Recently, competing endogenous RNAs (ceRNAs) hypothesis has gained a great interest in the study of molecular biological mechanisms of cancer occurrence and progression. However, studies on leukemia are limited, and there is still a lack of comprehensive analysis of lncRNA-miRNA-mRNA ceRNA regulatory network of AML based on high-throughput sequencing and large-scale sample size. We obtained RNA-Seq data and compared the expression profiles between 407 normal whole blood (GTEx) and 151 bone marrows of AML (TCGA). The similarity between two sets of genes with trait in the network was analyzed by weighted correlation network analysis (WGCNA). MiRcode, starBase, miRTarBase, miRDB and TargetScan was used to predict interactions between lncRNAs, miRNAs and target mRNAs. At last, we identified 108 lncRNAs, 10 miRNAs and 8 mRNAs to construct a lncRNA-miRNA-mRNA ceRNA network, which might act as prognostic biomarkers of AML. Among the network, a survival model with 8 target mRNAs (HOXA9+INSR+KRIT1+MYB+SPRY2+UBE2V1+WEE1+ZNF711) was set up by univariate and multivariate cox proportional hazard regression analysis, of which the AUC was 0.831, indicating its sensitivity and specificity in AML prognostic prediction. CeRNA networks could provide further insight into the study on gene regulation and AML prognosis.

Internal transcribed spacer 2 (ITS2) barcodes: A useful tool for identifying Chinese Zanthoxylum.

PREMISE OF THE STUDY: The genus Zanthoxylum in the Rutaceae family of trees and shrubs has a long history of domestication and cultivation in Asia for both economic and medicinal purposes. However, many Zanthoxylum species are morphologically similar and are easily confused. This often leads to false authentication of source materials and confusion in herbal markets, hindering their safe utilization and genetic resource conservation. DNA barcoding is a promising tool for identifying plant taxa. METHODS: We used three candidate DNA barcoding regions (ITS2, ETS, and trnH-psbA) to identify 69 accessions representing 13 Chinese Zanthoxylum species. The discriminatory capabilities of these regions were evaluated in terms of PCR amplification success, intra- and interspecific divergence, DNA barcoding gaps, and identification efficiency using the BLAST and tree-building methods. RESULTS: ITS2 proved the most useful for discriminating Chinese Zanthoxylum species, with a correct identification rate of 100%, and this region also exhibited significantly higher intra- and interspecific divergence. DISCUSSION: Phylogenetic analysis confirmed that ITS2 has a powerful discriminatory ability both at and below the species level. We confirmed that ITS2 is a powerful barcoding region for identifying Chinese Zanthoxylum species, and will be useful for analyzing and managing Chinese Zanthoxylum germplasm collections.

A novel compound heterozygous mutations in protein C gene causing neonatal purpura fulminans.

: Neonatal purpura fulminans is a rare, life-threatening disease caused by severe congenital deficiency of protein C (PC) because of homozygous or compound heterozygous mutations in the PROC gene. Mutation analysis plays a critical role in diagnosing the disorder and offering prenatal guidance. In this study, we identified a genetic defect in the PROC gene leading to neonatal purpura fulminans. The propositus had very low PC activity (4%) and PC antigen activity (5%). DNA screening of the whole PROC gene revealed two compound heterozygous mutations in exon8 (c.795_796insA) and exon9 (c.1206_1207insG). These two variations led to the compound heterozygous mutations of Gly266Argfs4 and Pro405Alafs20, which were inherited from the patient's father and mother, respectively. His older sister is heterozygous for the Gly266Argfs4 mutation. The inserted nucleotides alter the protein by introducing a stop codon at the subsequent AA position, resulting in a truncated protein compared with the wild type. We deduced that the compound heterozygous mutations are responsible for the PC deficiency, the Gly266Argfs4 mutation has been confirmed to be a novel mutation.

RSPO2 suppresses colorectal cancer metastasis by counteracting the Wnt5a/Fzd7-driven noncanonical Wnt pathway.

R-spondins play critical roles in development, stem cell survival, and tumorigenicity by modulating Wnt/ß-catenin signaling; however, the role of R-spondins in noncanonical Wnt signaling regulation remains largely unknown. We demonstrate here that R-spondin 2 (RSPO2) has an inhibitory effect on colorectal cancer (CRC) cell migration, invasion, and metastasis. Reduced RSPO2 expression was associated with tumor metastasis and poor survival in CRC patients. The metastasis-suppressive activity of RSPO2 was independent of the Wnt/ß-catenin signaling pathway but dependent on the Fzd7-mediated noncanonical Wnt signaling pathway. The physical interaction of RSPO2 and Fzd7 increased the degradation of cell surface Fzd7 via ZNRF3-mediated ubiquitination, which led to the suppression of the downstream PKC/ERK signaling cascade. In late-stage metastatic cancer, Wnt5a promoted CRC cell migration by preventing degradation of Fzd7, and RSPO2 antagonized Wnt5a-driven noncanonical Wnt signaling activation and tumor cell migration by blocking the binding of Wnt5a to the Fzd7 receptor. Our study reveals a novel RSPO2/Wnt5a-competing noncanonical Wnt signaling mechanism that regulates cellular migration and invasion, and our data suggest that secreted RSPO2 protein could serve as a potential therapy for Wnt5a/Fzd7-driven aggressive CRC tumors.

Aurora A Kinase Inhibitor AKI603 Induces Cellular Senescence in Chronic Myeloid Leukemia Cells Harboring T315I Mutation.

The emergence of resistance to imatinib mediated by mutations in the BCR-ABL has become a major challenge in the treatment of chronic myeloid leukemia (CML). Alternative therapeutic strategies to override imatinib-resistant CML are urgently needed. In this study, we investigated the effect of AKI603, a novel small molecule inhibitor of Aurora kinase A (AurA) to overcome resistance mediated by BCR-ABL-T315I mutation. Our results showed that AKI603 exhibited strong anti-proliferative activity in leukemic cells. AKI603 inhibited cell proliferation and colony formation capacities in imatinib-resistant CML cells by inducing cell cycle arrest with polyploidy accumulation. Surprisingly, inhibition of AurA by AKI603 induced leukemia cell senescence in both BCR-ABL wild type and T315I mutation cells. Furthermore, the induction of senescence was associated with enhancing reactive oxygen species (ROS) level. Moreover, the anti-tumor effect of AKI603 was proved in the BALB/c nude mice KBM5-T315I xenograft model. Taken together, our data demonstrate that the small molecule AurA inhibitor AKI603 may be used to overcome drug resistance induced by BCR-ABL-T315I mutation in CML.

A novel compound against oncogenic Aurora kinase A overcomes imatinib resistance in chronic myeloid leukemia cells.

Drug resistance still represents a major obstacle to successful chronic myeloid leukemia (CML) treatment and novel compounds or strategies to override this challenging problem are urgently required. Here, we evaluated a novel compound AKI603 against oncogenic Aurora kinase A (Aur-A) in imatinib-resistant CML cells. We found that Aur-A was highly activated in imatinib-resistant KBM5-T315I cells. AKI603 significantly inhibited the phosphorylation of Aur-A kinase at Thr288, while had little inhibitory effect on BCR-ABL kinase in both KBM5 and KBM5-T315I cells. AKI603 inhibited cell viability, and induced cell cycle arrest with polyploidy accumulation in KBM5 and KBM5-T315I cells. Moreover, inhibition of Aur-A kinase by AKI603 suppressed colony formation capacity without promoting obvious apoptosis. Importantly, AKI603 promoted cell differentiation in both CML cell types. Thus, our study suggested the potential clinical use of small molecule Aurora kinase inhibitor AKI603 to overcome imatinib resistance in CML treatment.