The Function and Mechanism of Long Non-Coding RNA RP11-23J9.4 in Thyroid Cancer.

INTRODUCTION: The objective of this research is to explore whether LncRNA RP11 23J9.4 can be used as a targeted marker for the treatment of thyroid cancer (TC), downregulation of LncRNA RP11 23J9.4 and X-ray radiation have synergistic inhibitory effect on TC. METHODS: The expression of LncRNA RP11 23J9.4 in papillary thyroid carcinoma (PTC) cell was downregulated by cell transfection, and its inhibitory effect on PTC cells was proved through proliferation, invasion experiment, apoptosis, and cell cycle analysis. The transfected cells were irradiated with 2 Gy X-ray. The above methods were also used to detect whether they had synergistic inhibitory effect on TC. The expression of Axin2 gene and protein were detected by real-time PCR, Western blotting, and immunohistochemistry. RESULTS: On the one hand, it is proved that downregulating the expression of LncRNA RP11 23J9.4 can inhibit the development of TC through Axin2. On the other hand, it is clear that downregulation of LncRNA RP11 23J9.4 and X-ray radiation have synergistic inhibitory effect on TC. CONCLUSIONS: LncRNA RP11 23J9.4 and X-ray have significant synergistic effect on TC. LncRNA RP11 23J9.4 can be used as a marker for TC targeted therapy.

Benign but fatal: management of endotracheal Rosai-Dorfman disease with acute onset.

Rosai-Dorfman disease (RDD) is a non-malignant condition mainly manifesting as a proliferation of histiocytes in lymph nodes. Endotracheal RDD (ERDD) with an acute onset presentation is extremely rare. There are few case reports of ERDD mainly concerning its pathology, diagnostics and bronchoscopic treatment, without providing sufficient clinical information from a comprehensive perspective. As a novel and challenging technique, tracheal resection and reconstruction (TRR) with spontaneous-ventilation video-assisted thoracoscopic surgery (SV-VATS) has been reported as feasible and safe in highly selected patients, but few centres have shared their experience with this approach. This case-based discussion includes not only practical issues in the management of a life-threatening ERDD patient, but also specialists' views on the management of acute obstructive airway, and the surgeons' reflection on TRR with SV-VATS.

miR-122-5p Promotes Peripheral and Central Nervous System Inflammation in a Mouse Model of Intracerebral Hemorrhage via Disruption of the MLLT1/PI3K/AKT Signaling.

Intracerebral hemorrhage (ICH) is a recognized central nervous system inflammation complication. Several microRNAs (miRNAs or miRs) have been documented to be vital modulators in peripheral and central nervous system inflammation. Based on whole transcriptome sequencing and bioinformatics analysis, this study aims to reveal the possible molecular mechanisms by which miR-122-5p affects the inflammatory response in the peripheral and central nervous system in a mouse model of ICH. Differentially expressed ICH-related miRNAs were screened. Adeno-associated viral vectors were used to knock down miR-122-5p in mice to evaluate the effect of miR-122-5p on peripheral and central nervous system inflammation. The downstream target gene of miR-122-5p was analyzed. Neurons were isolated from mice and treated with hemin to construct an in vitro model of ICH, followed by transduction with miR-122-5p mimic or combined with oe-MLLT1. The neurons were then co-cultured with microglia BV2 to assess their activation. It was found that miR-122-5p was highly expressed in ICH, and MLLT1 was lowly expressed. In vivo experiments showed that miR-122-5p knockdown decreased neurological deficits, BBB permeability, and inflammation in the peripheral and central nervous system in ICH mice. It involved its binding to MLLT1 and downregulation of the activity of the PI3K/AKT pathway. In vitro data exhibited that miR-122-5p stimulated the generation of inflammatory factors and microglia activation by targeting MLLT1 and inhibiting the PI3K/AKT pathway. Collectively, our work reveals a novel miR-122-5p/MLLT1-mediated regulatory network in ICH that may be a viable target for neuroinflammation alleviation.

Enhancer-driven transcription of MCM8 by E2F4 promotes ATR pathway activation and glioma stem cell characteristics.

BACKGROUND: Glioma stem cells (GSCs) are responsible for glioma recurrence and drug resistance, yet the mechanisms underlying their maintenance remains unclear. This study aimed to identify enhancer-controlled genes involved in GSCs maintenance and elucidate the mechanisms underlying their regulation. METHODS: We analyzed RNA-seq data and H3K27ac ChIP-seq data from GSE119776 to identify differentially expressed genes and enhancers, respectively. Gene Ontology analysis was performed for functional enrichment. Transcription factors were predicted using the Toolkit for Cistrome Data Browser. Prognostic analysis and gene expression correlation was conducted using the Chinese Glioma Genome Atlas (CGGA) data. Two GSC cell lines, GSC-A172 and GSC-U138MG, were isolated from A172 and U138MG cell lines. qRT-PCR was used to detect gene transcription levels. ChIP-qPCR was used to detect H3K27ac of enhancers, and binding of E2F4 to target gene enhancers. Western blot was used to analyze protein levels of p-ATR and γH2AX. Sphere formation, limiting dilution and cell growth assays were used to analyze GSCs growth and self-renewal. RESULTS: We found that upregulated genes in GSCs were associated with ataxia-telangiectasia-mutated-and-Rad3-related kinase (ATR) pathway activation, and that seven enhancer-controlled genes related to ATR pathway activation (LIN9, MCM8, CEP72, POLA1, DBF4, NDE1, and CDKN2C) were identified. Expression of these genes corresponded to poor prognosis in glioma patients. E2F4 was identified as a transcription factor that regulates enhancer-controlled genes related to the ATR pathway activation, with MCM8 having the highest hazard ratio among genes positively correlated with E2F4 expression. E2F4 bound to MCM8 enhancers to promote its transcription. Overexpression of MCM8 partially restored the inhibition of GSCs self-renewal, cell growth, and the ATR pathway activation caused by E2F4 knockdown. CONCLUSION: Our study demonstrated that E2F4-mediated enhancer activation of MCM8 promotes the ATR pathway activation and GSCs characteristics. These findings offer promising targets for the development of new therapies for gliomas.

Targeting E3 Ubiquitin Ligase WWP1 Prevents Cardiac Hypertrophy Through Destabilizing DVL2 via Inhibition of K27-Linked Ubiquitination.

BACKGROUND: Without adequate treatment, pathological cardiac hypertrophy induced by sustained pressure overload eventually leads to heart failure. WWP1 (WW domain-containing E3 ubiquitin protein ligase 1) is an important regulator of aging-related pathologies, including cancer and cardiovascular diseases. However, the role of WWP1 in pressure overload-induced cardiac remodeling and heart failure is yet to be determined. METHODS: To examine the correlation of WWP1 with hypertrophy, we analyzed WWP1 expression in patients with heart failure and mice subjected to transverse aortic constriction (TAC) by Western blotting and immunohistochemical staining. TAC surgery was performed on WWP1 knockout mice to assess the role of WWP1 in cardiac hypertrophy, heart function was examined by echocardiography, and related cellular and molecular markers were examined. Mass spectrometry and coimmunoprecipitation assays were conducted to identify the proteins that interacted with WWP1. Pulse-chase assay, ubiquitination assay, reporter gene assay, and an in vivo mouse model via AAV9 (adeno-associated virus serotype 9) were used to explore the mechanisms by which WWP1 regulates cardiac remodeling. AAV9 carrying cardiac troponin T (cTnT) promoter-driven small hairpin RNA targeting WWP1 (AAV9-cTnT-shWWP1) was administered to investigate its rescue role in TAC-induced cardiac dysfunction. RESULTS: The WWP1 level was significantly increased in the hypertrophic hearts from patients with heart failure and mice subjected to TAC. The results of echocardiography and histology demonstrated that WWP1 knockout protected the heart from TAC-induced hypertrophy. There was a direct interaction between WWP1 and DVL2 (disheveled segment polarity protein 2). DVL2 was stabilized by WWP1-mediated K27-linked polyubiquitination. The role of WWP1 in pressure overload-induced cardiac hypertrophy was mediated by the DVL2/CaMKII/HDAC4/MEF2C signaling pathway. Therapeutic targeting WWP1 almost abolished TAC induced heart dysfunction, suggesting WWP1 as a potential target for treating cardiac hypertrophy and failure. CONCLUSIONS: We identified WWP1 as a key therapeutic target for pressure overload induced cardiac remodeling. We also found a novel mechanism regulated by WWP1. WWP1 promotes atypical K27-linked ubiquitin multichain assembly on DVL2 and exacerbates cardiac hypertrophy by the DVL2/CaMKII/HDAC4/MEF2C pathway.

Vascular smooth muscle cell-specific miRNA-214 knockout inhibits angiotensin II-induced hypertension through upregulation of Smad7.

Vascular remodeling is a prominent trait during the development of hypertension, attributable to the phenotypic transition of vascular smooth muscle cells (VSMCs). Increasing studies demonstrate that microRNA plays an important role in this process. Here, we surprisingly found that smooth muscle cell-specific miR-214 knockout (miR-214 cKO) significantly alleviates angiotensin II (Ang II)-induced hypertension, which has the same effect as that of miR-214 global knockout mice in response to Ang II stimulation. Under the treatment of Ang II, miR-214 cKO mice exhibit substantially reduced systolic blood pressure. The vascular medial thickness and area in miR-214 cKO blood vessels were obviously reduced, the expression of collagen I and proinflammatory factors were also inhibited. VSMC-specific deletion of miR-214 blunts the response of blood vessels to the stimulation of endothelium-dependent and -independent vasorelaxation and phenylephrine and 5-HT induced vasocontraction. In vitro, Ang II-induced VSMC proliferation, migration, contraction, hypertrophy, and stiffness were all repressed with miR-214 KO in VSMC. To further explore the mechanism of miR-214 in the regulation of the VSMC function, it is very interesting to find that the TGF-ß signaling pathway is mostly enriched in miR-214 KO VSMC. Smad7, the potent negative regulator of the TGF-ß/Smad pathway, is identified to be the target of miR-214 in VSMC. By which, miR-214 KO sharply enhances Smad7 levels and decreases the phosphorylation of Smad3, and accordingly alleviates the downstream gene expression. Further, Ang II-induced hypertension and vascular dysfunction were reversed by antagomir-214. These results indicate that miR-214 in VSMC established a crosstalk between Ang II-induced AT1R signaling and TGF-ß induced TßRI /Smad signaling, by which it exerts a pivotal role in vascular remodeling and hypertension and imply that miR-214 has the potential as a therapeutic target for the treatment of hypertension.

Diagnostic accuracy of DNA-based SDC2 methylation test in colorectal cancer screening: a meta-analysis.

BACKGROUND: A growing body of research suggests that methylated genes can be used as early diagnostic markers for cancer. Some studies on methylated Syndecan 2 (SDC2) have shown that it has a great diagnostic ability in colorectal cancer. This meta-analysis was aimed to estimate the diagnostic performance of methylated SDC2 as a potential novel biomarker to screen for the colorectal cancer. METHODS: Two independent researchers conducted a comprehensive literature search to identify all relevant studies on SDC2 methylation for the diagnosis of colorectal cancer from inception to March 1, 2021. By using STATA and Revman software, the data were analyzed using a Bivariate mixed model. The quality of each study was also evaluated. RESULTS: A total of 12 studies comprised of 1574 colorectal cancer patients and 1945 healthy people were included in our meta-analysis. Bivariate analysis showed a pooled sensitivity of 0.81 [95% confidence interval (CI) 0.74-0.86], specificity of 0.95 (95% CI 0.93-0.96), positive likelihood ratio of 15.29 (95% CI 10.83-21.60), and negative likelihood ratio of 0.21 (95% CI 0.15-0.27). The diagnostic odds ratio and the area under the summary ROC curve for diagnosing colorectal cancer were 74.42 (95% CI45.44-121.89) and 0.96 (95% CI 0.94-0.97), respectively. For adenomas, the pooled sensitivity and specificity were 0.47 (95% CI 0.34-0.61) and 0.95 (95% CI 0.92-0.97), respectively. CONCLUSIONS: Our analysis revealed that methylated SDC2 could be considered as a potential novel biomarker to screen for colorectal cancer.

3' untranslated region of Ckip-1 inhibits cardiac hypertrophy independently of its cognate protein.

AIMS: 3' untranslated region (3' UTR) of mRNA is more conserved than other non-coding sequences in vertebrate genomes, and its sequence space has substantially expanded during the evolution of higher organisms, which substantiates their significance in biological regulation. However, the independent role of 3' UTR in cardiovascular disease was largely unknown. METHODS AND RESULTS: Using bioinformatics, RNA fluorescent in situ hybridization and quantitative real-time polymerase chain reaction, we found that 3' UTR and coding sequence regions of Ckip-1 mRNA exhibited diverse expression and localization in cardiomyocytes. We generated cardiac-specific Ckip-1 3' UTR overexpression mice under wild type and casein kinase 2 interacting protein-1 (CKIP-1) knockout background. Cardiac remodelling was assessed by histological, echocardiography, and molecular analyses at 4 weeks after transverse aortic constriction (TAC) surgery. The results showed that cardiac Ckip-1 3' UTR significantly inhibited TAC-induced cardiac hypertrophy independent of CKIP-1 protein. To determine the mechanism of Ckip-1 3' UTR in cardiac hypertrophy, we performed transcriptome and metabolomics analyses, RNA immunoprecipitation, biotin-based RNA pull-down, and reporter gene assays. We found that Ckip-1 3' UTR promoted fatty acid metabolism through AMPK-PPARα-CPT1b axis, leading to its protection against pathological cardiac hypertrophy. Moreover, Ckip-1 3' UTR RNA therapy using adeno-associated virus obviously alleviates cardiac hypertrophy and improves heart function. CONCLUSIONS: These findings disclose that Ckip-1 3' UTR inhibits cardiac hypertrophy independently of its cognate protein. Ckip-1 3' UTR is an effective RNA-based therapy tool for treating cardiac hypertrophy and heart failure.

Effect of MicroRNA-210 on the Growth of Ovarian Cancer Cells and the Efficacy of Radiotherapy.

OBJECTIVE: The objective of this study is to explore the role of miR-210 in the growth of ovarian cancer cells and the correlation with radiotherapy and to elucidate underlying molecular mechanisms. METHODS: Human ovarian cancer cell lines OVCAR3 and SKOV3 were cultured in vitro, and miR-210 over-expression and low-expression ovarian cancer cell models were established by cell transfection. MTT assay was used to detect the proliferation activity. Transwell was used to detect the migration and invasion abilities. Western blot measured the expression of proteins related to cell proliferation, migration, and invasion. The cells were treated with different doses of ionizing radiation, and then the cell proliferation activity was detected by MTT. The expression of apoptosis-related proteins was detected by Western blot. The Caspase-Glo® Kit was used to detect the activity of cellular caspase 3/7 enzymes. RESULTS: The proliferation, migration, and invasion abilities of miR-210 over-expression ovarian cancer cells were increased (p < 0.05), the expressions of PTEN and E-cadherin were decreased, and the expression of p-Protein kinase B (AKT), N-cadherin, Snail, and Vimentin were elevated. After ionizing radiation, the sensitivity of miR-210 over-expression cells to radiotherapy was decreased, the expression of apoptosis-related protein Bax was decreased, the expression of Bcl-2 was increased, and the activity of cellular caspase 3/7 enzyme was reduced (p < 0.05). CONCLUSION: miR-210 can promote the proliferation, migration, and invasion of ovarian cancer cells by activating the AKT signaling pathway and regulating the expression of Epithelial-mesenchymal transition-related proteins. miR-210 can reduce the sensitivity of ovarian cancer cells to radiotherapy by inhibiting apoptosis, which might serve as a potential target for the treatment of ovarian tumors.

Long noncoding RNAs as diagnostic biomarkers for the early detection of digestive tract cancers: a systematic review and meta-analysis.

BACKGROUND: long noncoding RNAs (lncRNAs) have attracted attention recently. However, many inconsistencies frequently appeared for the early diagnosis of digestive tract cancers (DTCs). We performed this meta-analysis to describe the diagnostic performance of lncRNAs in the discrimination of DTCs. METHODS: data were extracted from PubMed, Web of Science, Embase, and Cochrane Library. Their quality was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Such parameters as sensitivity and specificity were included for pooled analyses. The STATA 12.0 and Meta-Disc 1.4 software packages were used to perform the statistical analysis. RESULTS: sixty-nine papers were included in this meta-analysis. The pooled analysis of DTCs showed that lncRNAs had a sensitivity of 0.78 and a specificity of 0.80. The area under the summary ROC curve (AUC) was 0.86. For gastric cancer (GC), the pooled sensitivity and specificity were 0.77 (95 % CI: 0.72-0.81) and 0.75 (95 % CI: 0.71-0.79), respectively, and the AUC was 0.83. For colorectal cancer (CRC), these three parameters were 0.82 (95 % CI: 0.76-0.86), 0.84 (95 % CI: 0.79-0.88), and 0.90, respectively. For esophageal cancer (EC) sensitivity was 0.74 (95 % CI: 0.67-0.80) and specificity reached 0.86 (95 % CI: 0.72-0.93), with an AUC of 0.82. CONCLUSIONS: LncRNAs show potential diagnostic value for discrimination between DTCs.

Silencing of long noncoding RNA RP11-476D10.1 enhances apoptosis and autophagy while inhibiting proliferation of papillary thyroid carcinoma cells via microRNA-138-5p-dependent inhibition of LRRK2.

The distant metastasis in papillary thyroid carcinoma (PTC) is a major threat for PTC patients. Moreover, the involvement of long noncoding RNAs (lncRNAs) in the regulation of PTC progression has been extensively investigated. The aim of this study was to underscore whether lncRNA RP11-476D10.1 affects the proliferation, apoptosis and autophagy of PTC cells. Initially, we determined that lncRNA RP11-476D10.1 and LRRK2 were highly expressed in PTC cells. Meanwhile, through experimentation, miR-138-5p was confirmed to bind with lncRNA RP11-476D10.1 and LRRK2. It was also revealed that lncRNA RP11-476D10.1 downregulated the miR-138-5p expression, thereby upregulating the LRRK2 expression. After that, PTC cells were transfected with siRNA against RP11-476D10.1, or inhibitor or mimic of miR-138-5p to evaluate the influence of lncRNA RP11-476D10.1 on the PTC cell proliferation, apoptosis, and autophagy in vitro and on the tumor formation ability in vivo. The results showed that silenced lncRNA RP11-476D10.1 or overexpressed miR-138-5p enhanced the apoptosis and autophagy of PTC cells while reducing cell proliferation, with increased levels of Bax, LC3B, and Beclin1 and decreased Bcl-2 level were observed. The inhibitory role of silenced lncRNA RP11-476D10.1 role in the PTC development was further verified by the reduced tumor formation ability in nude mice. Our results demonstrated that lncRNA RP11-476D10.1 could bind to miR-138-5p and promote LRRK2 expression. Moreover, the silencing of lncRNA RP11-476D10.1 may inhibit the development of PTC, highlighting a novel insight for the development of superior therapeutic targets for PTC treatment.

Assessment of risk based on variant pathways and establishment of an artificial neural network model of thyroid cancer.

BACKGROUND: This study aimed to establish an artificial neural network (ANN) model based on variant pathways to predict the risk of thyroid cancer. METHODS: The RNASeq data of 482 thyroid cancer samples were downloaded from the TCGA database. The samples were divided into low-risk and high-risk groups, followed by identification of differentially expressed genes (DEGs). Co-expression analysis and pathway enrichment analysis were then performed. The variant pathways were screened according to the functional deviation score of each pathway, and an ANN model was established. Finally, the efficiency of the ANN model for risk assessment was validated by survival analysis and analysis of an independent microarray dataset (GSE34289) for thyroid cancer. RESULTS: In total, 190 DEGs (85 up-regulated and 105 down-regulated) were identified between the low-risk and high-risk groups. Ten risk-related variant pathways were identified between the low-risk and high-risk groups, which were related to inflammatory and immune responses. Based on these variant pathways, an ANN model was built, consisting of an input layer, two hidden layers, and an output layer, corresponding to 15, 8, 5, and 1 neuron, respectively. Survival analysis showed that this model could effectively distinguish the samples with different risks. Analysis of microarray dataset GSE34289 showed that the accuracy of this model for predicating low-risk and high-risk samples was 77.5 and 86.0%, respectively. CONCLUSIONS: This study suggests that the ANN model based on variant pathways can be used for effectively evaluating the risk of thyroid cancer.

Down-regulation of microRNA-31-5p inhibits proliferation and invasion of osteosarcoma cells through Wnt/ß-catenin signaling pathway by enhancing AXIN1.

OBJECTIVES: Recently, the role of microRNA-31-5p (miR-31-5p) in gene expression regulation has been reported in various cancers. Studies have shown that Wnt/ß-catenin signaling pathway is involved in the proliferation and invasion of osteosarcoma (OS) cells. Therefore, this study aims to probe into the regulatory role of miR-31-5p targeting AXIN1 in OS cells through Wnt/ß-catenin signaling pathway. METHODS: Firstly, microarray expression profiles were used to screen differentially expressed miRNAs associated with OS. Next, OS and normal fibrous connective tissues as well as OS cell lines were obtained for investigating the role of miR-31-5p on OS. Then, the putative binding sites between miR-31-5p and AXIN1 were predicted and verified. The regulatory effects of miR-31-5p on proliferation and invasion as well as tumorigenic potential of OS cells targeting AXIN1 were also analyzed. Besides, the relationship between miR-31-5p and Wnt/ß-catenin signaling pathway was assessed by immunofluorescence staining. RESULTS: The microarray dataset GSE63939 showed that miR-31-5p and AXIN1 were involved in OS. miR-31-5p expression increased while the expression of AXIN1 decreased in OS tissues and cells. AXIN1 was identified as a target gene of miR-31-5p, intense expression of which inhibited the transcription of AXIN1. Down-regulated miR-31-5p suppressed proliferation, invasion and tumorigenicity of OS cells through promoting AXIN1. Decreased miR-31-5p activated Wnt/ß-catenin signaling pathway, as reflected by increased ß-catenin translocation into nuclei, through up-regulating the transcription of AXIN1. CONCLUSIONS: All in all, repression of miR-31-5p targets AXIN1 to activate the Wnt/ß-catenin signaling pathway, thus suppressing proliferation, invasion and tumorigenicity of OS cells.

DIAGNOSTIC VALUE OF ANTI-MÜLLERIAN HORMONE AS A BIOMARKER FOR POLYCYSTIC OVARY SYNDROME: A META-ANALYSIS UPDATE.

Objective: A previous meta-analysis carried out on the predictive ability of anti-Müllerian hormone (AMH) for polycystic ovary syndrome (PCOS) showed that independent AMH may be a useful initial diagnostic test for PCOS. The aims of this study were to update the meta-analysis and to evaluate the diagnostic efficacy of AMH when it replaces polycystic ovary morphology (PCOM) in the Rotterdam criteria. Methods: Two independent reviewers searched PubMed, Cochrane Library, and the Web of Science databases systematically to identify relevant articles by using the key words "anti-Müllerian hormone" and "polycystic ovary syndrome." The deadline for manuscript inclusion was July 31, 2018. A random effects model was used and subgroup analysis and meta regression were performed to identify possible sources of heterogeneity. The methodologic quality of each study was assessed by QUADAS-2 and funnel plot asymmetry test. Results: According to the inclusion criteria, 29 studies were included in this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) for AMH alone detecting PCOS were 0.76 (95% confidence interval [CI] 0.71 to 0.81), 0.86 (95% CI 0.82 to 0.90) and 20 (95% CI 12 to 33), respectively. When AMH replaces polycystic ovary morphology (PCOM) for the diagnosis of PCOS, the pooled sensitivity, specificity, and DOR rose to 0.93 (95% CI 0.89 to 0.96), 0.99 (95% CI 0.95 to 1.00), and 1,634 (95% CI 217 to 12,324), respectively. The area under the summary receiver-operating characteristic curve for AMH alone and for AMH replacing PCOM detecting PCOS were 0.88 (95% CI 0.85 to 0.91) and 0.97 (95% CI 0.95 to 0.98), respectively, which was found to be significantly different (Z = 4.89, P<.01). Conclusion: When AMH replaces PCOM in the Rotterdam criteria, the diagnostic efficacy for polycystic ovary syndrome is better. Abbreviations: AMH = anti-Müllerian hormone; AUC = area under the summary receiver operating characteristic curve; BMI = body mass index; CI = confidence interval; DOR = diagnostic odds ratio; HA = hyperandrogenism; IBC = Immunotech-Beckman Coulter; NLR = negative likelihood ratio; OA = oligo-anovulation; PCOM = polycystic ovary morphology; PCOS = polycystic ovary syndrome; PLR = positive likelihood ratio; QUADAS = the Quality Assessment of Diagnostic Accuracy Studies; SENS = sensitivity; SPEC = specificity.

A Case of Klebsiella pneumoniae infection.

INTRODUCTION: In recent years, hypervirulent Klebsiella pneumoniae (hvKp) has attracted increasing attention. It usually causes liver abscesses, which spread through the bloodstream to other parts such as the eyes, brain, lungs. 5.5% of all paroxysmal sympathetic hyperactivity syndrome are associated with infection, hydrocephalus, brain tumors, and some unknown causes. Younger patients with focal lesions of the brain parenchyma are at higher risk of paroxysmal sympathetic hyperactivity (PSH). CASE PRESENTATION: This case report details the clinical features of Klebsiella pneumoniae diagnosed in a healthy individual. In addition to liver abscesses, bacteremia, and hyperglycemia, there are also brain abscesses, hernias, and postoperative paroxysmal sympathetic hyperactivity, an unexpected association between diseases or symptoms. The patient stabilized after comprehensive treatment, including early drainage of abscesses, rapid pathogen diagnosis, and timely and appropriate antibiotics. At a two-month follow-up, no signs of infection recurrence were noted, and the patient regained neurological function and could participate in regular physical activity. DISCUSSION: Symptoms of Klebsiella pneumoniae infection usually appear gradually, and misdiagnosis is common. When young patients suddenly develop high fever and abscess at a particular site, Klebsiella pneumoniae infection should be considered routine. Paroxysmal sympathetic hyperactivity syndrome caused by infection is rare, but a clinical score (PSH assessment measure, PSH-AM score) should be performed when clinical features appear. Early diagnosis and treatment can improve the prognosis.

Cerebral venous thrombosis in patients with Sjögren's syndrome: A case report and literature review.

Although cerebral venous thrombosis (CVT) is known to be induced by autoimmune diseases such as systemic lupus erythematosus and antiphospholipid syndrome, CVT caused by Sjögren's syndrome (SS) is scarcely reported in the medical literature. Since the first report of SS-induced CVT in 1994, only five cases have been reported, and the clinicopathological features of the disease are not well documented. We herein present a case report of a 41-year-old woman who was diagnosed with SS-induced CVT and perform a literature review of six cases of SS-induced CVT with a discussion of the pathogenesis, features of clinic symptoms, treatment, and prognosis of SS-associated CVT. We aim to improve the understanding of SS-induced CVT among clinicians and reduce the incidence of missed clinical diagnoses.

Diagnosis and Treatment of Keloid: Method Summary and Effect Evaluation.

Keloid is a prevalent skin disorder characterized by the abnormal growth of keloid tissue, which usually occurs following wound healing or surgical incisions. It typically progresses through several stages: the inflammatory stage, the proliferative stage, collagen remodeling, and ultimately the formation of keloid. This review aims to summarize the diagnostic and therapeutic methods for keloid, and evaluate their effectiveness. The diagnosis of keloid is usually based on medical history and clinical manifestations such as pain, itching, erythema, and induration. Other commonly used diagnostic methods include tissue biopsy and ultrasound examination. Various treatment options for keloid exist, including physical therapy, medication, surgical treatment, and radiation therapy. Physical therapy includes pressure therapy, laser therapy, such as silicone sheets, elastic bandages, and laser irradiation. Medication treatment mainly involves the application of topical medications or intralesional injections, such as topical corticosteroids, 5-fluorouracil, and others. Radiation therapy can be administered using applicators and superficial radiation therapy, among other methods. The treatment outcomes of keloid vary from person to person and recurrence is common. Therefore, a comprehensive treatment approach may be the most effective strategy. Individualized treatment plans should consider factors such as the patient's age, gender, medical history, and the severity of the condition. In conclusion, the diagnosis and treatment of keloid require consideration of multiple factors and the implementation of individualized treatment plans. Future research should focus on identifying the molecular mechanisms underlying the occurrence and progression of keloid in order to develop more effective treatment methods.

Treatment-free survival after discontinuation of immune checkpoint inhibitors in mNSCLC: a systematic review and meta-analysis.

Background: Recent research has suggested that patients with metastatic non-small cell lung cancer (mNSCLC) can achieve ongoing response after discontinuation of immune checkpoint inhibitor (ICI), but the best time to discontinue and the factors influencing efficacy remain unknown. Method: A systematic search was performed for prospective clinical trials in patients with mNSCLC treated with ICIs published up to July 10, 2022. Eligible studies reported treatment-free survival (TFS) after discontinuation of ICI in partial objective responders. We calculated objective response rate (ORR) and TFS using random-effects models with respective 95% confidence intervals (Cis), and performed subgroup analyses to discuss the specific associations between ORR and TFS and the associated influencing factors. Results: Across the 26 cohorts (3833 patients) included, the weighted mean ORR for all patients was 29.30% (95% CI 24.28% to 34.57%), with ICI plus chemotherapy (48.83%, 95% CI 44.36% to 53.30%) significantly higher than monotherapy (23.40%, 95% CI 18.53% to 28.62%). 395 patients were all patients who were complete or partial responders in the study, 194 discontinued ICI treatment, and nearly 35.5% achieved a durable response. No significant differences in TFS were found between subgroups according to the ICI regimen classification. Four cohorts of patients who completed 35 courses of treatment showed high levels of pooled TFS at 6 (80.18%, 95% CI 53.03% to 97.87%) and 12 months (66.98%, 95% CI 46.90% to 84.47%). Three cohorts of patients discontinued ICI treatment due to treatment-related adverse events (TRAEs) with the TFS rates at 6 (76.98%, 95% CI 65.79% to 86.65%) and 12 months (64.79%, 95% CI 50.20% to 78.19%). Conclusion: Patients with mNSCLC were able to achieve ongoing responses after discontinuation of ICI. In conclusion, the results of this meta-analysis indicate that different treatment regimens, different drugs or different treatment durations may have an impact on TFS.

Long Noncoding RNAs in Ovarian Cancer-Functions and Clinical Applications.

Long noncoding RNAs (lncRNAs) are RNA molecules with a length of more than 200 nt that have been discovered in recent years. LncRNAs can participate in regulating gene expression and various biological activities through multiple pathways, such as at the epigenetic level, transcriptional level, and posttranscriptional level. In recent years, with the increasing understanding of lncRNAs, a large number of studies have shown that lncRNAs are closely related to ovarian cancer and participate in its occurrence and development, providing a new method to investigate ovarian cancer. In this review, we analyzed and summarized the relationship between various lncRNAs and ovarian cancer in terms of occurrence, development, and clinical significance, in order to provide a theoretical basis for basic research and clinical application of ovarian cancer.

Combined Effects of Programmed Cell Death-1 Blockade and Endostar on Brain Metastases of Lung Cancer.

BACKGROUND: The blockade of programmed cell death-1 (PD-1) and recombinant human endostatin can be used for the treatment of non-small cell lung cancer (NSCLC) and its metastasis. This study aims to explore the therapeutically potential of PD-1 blockade plus Endostar in brain metastasis of NSCLC. METHODS: The mouse brain metastases model was established using Lewis lung carcinoma luciferase (LLC-Luc) and PC-9-Luc cells. Tumor metastasis in the brain and tumor burden were analyzed by using bioluminescence imaging (BLI), qRT-PCR and ELISA which were used to determine the mRNA and protein levels of biomarkers in tumor tissues. Immunohistochemical staining was used to determine the expression and location of CD31 in tumor tissues in the brain. RESULTS: Treatment with anti-PD-1 and Endostar suppressed tumor metastasis in the brain and prolonged overall survival rate in LLC-Luc and PC-9-Luc brain metastases mouse model. In addition, treatment with anti-PD-1 and Endostar inhibited the expressions of CD31 and VEGF in tumor tissues in the brain. Furthermore, treatment with anti-PD- 1 and Endostar significantly suppressed the levels of IL1ß, IFNγ, and TGFß in the tumor tissues. CONCLUSION: The combination of PD-1 blockade and endostar suppressed brain metastases of NSCLC.