[Analysis of risk factors of short-term prognosis in patients with severe Budd-Chiari syndrome].

Objective: To explore the risk factors of short-term prognosis of severe Budd-Chiari syndrome (BCS) patients,established and verified the nomogram prediction model for these BCS patients and evaluated its clinical application value. Methods: This study is a retrospective cohort study. The clinical data of 171 patients with severe BCS diagnosed were retrospectively analyzed in the Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023. There were 105 males and 66 females, aged (52.1±12.8) years (range: 18 to 79 years). The patients were divided into two groups based on whether they died within 28 days: the death group (n=38) and the survival group (n=133). The risk factors for short-term death of patients were analyzed,and independent risk factors were screened by univariate and multivariate analysis. Furthermore,these factors were used to establish the nomogram prediction model. The area under the curve(AUC),the Bootstrap Resampling,the Hosmer-Lemeshow test and the Decision Curve Analysis(DCA) were used to verify the model's differentiation,internal verification,calibration degree and clinical effectiveness,respectively. Results: Univariate and multivariate Logistics regression analysis showed that the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time were independent risk factors (P<0.05). The above factors were used to successfully establish the prediction model with 0.908 of AUC and 0.895 of the internal verification of AUC,indicating that the predictive model was valuable. The 0.663 P-values in the Hosmer-Lemeshow test indicated the high calibration degree of the model. The clinical effectiveness of the model was proved by the 18% clinical benefit population using the DCA curve with the 17% probability threshold. Conclusions: The independent risk factors are the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time. An adequate basis was acquired by establishing a nomogram prediction model of the short-term prognosis of severe BCS,which was helpful for early clinical screening and identification of high-risk patients with severe BCS who could die in the short term and timely providing timely intervention measures for improving the prognosis.

Cognitive functioning in untreated glioma patients: The limited predictive value of clinical variables.

BACKGROUND: Previous research identified many clinical variables that are significantly related to cognitive functioning before surgery. It is not clear whether such variables enable accurate prediction for individual patients' cognitive functioning because statistical significance does not guarantee predictive value. Previous studies did not test how well cognitive functioning can be predicted for (yet) untested patients. Furthermore, previous research is limited in that only linear or rank-based methods with small numbers of variables were used. METHODS: We used various machine learning models to predict preoperative cognitive functioning for 340 patients with glioma across 18 outcome measures. Predictions were made using a comprehensive set of clinical variables as identified from the literature. Model performances and optimized hyperparameters were interpreted. Moreover, Shapley additive explanations were calculated to determine variable importance and explore interaction effects. RESULTS: Best-performing models generally demonstrated above-random performance. Performance, however, was unreliable for 14 out of 18 outcome measures with predictions worse than baseline models for a substantial number of train-test splits. Best-performing models were relatively simple and used most variables for prediction while not relying strongly on any variable. CONCLUSIONS: Preoperative cognitive functioning could not be reliably predicted across cognitive tests using the comprehensive set of clinical variables included in the current study. Our results show that a holistic view of an individual patient likely is necessary to explain differences in cognitive functioning. Moreover, they emphasize the need to collect larger cross-center and multimodal data sets.

[C2 pedicle screw insertion assisted by mobilization of the vertebral artery in cases with high-riding vertebral artery].

Objective: To examine the feasibility, safety, and efficacy of mobilization of the vertebral artery for C2 pedicle screws in cases with high-riding vertebral artery (HRVA). Methods: The clinical data of 12 patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial reduction and fixation in the Department of Neurosurgery, the First Affiliated Hospital of University of Science and Technology of China between January 2020 and November 2021 were retrospectively analyzed. All patients had high-riding vertebral artery on at least one side that prohibited the insertion of C2 pedicle screws. There were 2 males and 10 females aged (48.0±12.8) years (range: 17 to 67 years). After correction of vertical dislocation during the operation, the C2 pedicle screw insertion and occipitocervical fixation and fusion were performed using the vertebral artery mobilization technique. Neurological function was assessed using the Japanese Orthopedic Association (JOA) scale. The preoperative and postoperative JOA score and the main radiological measurements, including the anterior atlantodental interval (ADI), the distance of the odontoid tip above the Chamberlain line, the clivus-canal angle, were collected and compared by paired t-test. Results: Mobilization of the high-riding vertebral artery was successfully completed, and C2 pedicle screws were then fulfilled after the vertebral artery was protected. There was no injury to the vertebral artery during the operation. Meanwhile, no severe surgical complications such as cerebral infarction or aggravated neurological dysfunction occurred during the perioperative period. Satisfactory C2 pedicle screw placement and reduction were achieved in all 12 patients. All patients achieved bone fusion 6 months after surgery. No looseness and shift in internal fixation or reduction loss was observed during the follow-up period. Compared to the preoperative, the postoperative ADI decreased from (6.1±1.9) mm to (2.0±1.2) mm (t=6.73, P<0.01), the distance of the odontoid tip above the Chamberlain line decreased from (10.4±2.5) mm to (5.5±2.3) mm (t=7.12, P<0.01), the clivus-canal angle increased from (123.4±11.1) ° to (134.7±9.6) ° (t=2.50, P=0.032), the JOA score increased from 13.3±2.1 to 15.6±1.2 (t=6.99, P<0.01). Conclusion: The C2 pedicle screw insertion assisted by mobilization of the vertebral artery is safe and considerably effective, providing a choice for internal fixation in cases with high-riding vertebral arteries.

Outcomes of adolescents with acute lymphoblastic leukaemia.

INTRODUCTION: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL. METHODS: We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015. RESULTS: Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents [10-14 years] and 45 older adolescents [15-18 years]). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD. CONCLUSION: Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL.

One hundred citation classics in benign anorectal disease: a bibliometric analysis of seven decades (1950-2019) / Cem clássicos de citações em doença anorretal benigna: uma análise bibliométrica de sete décadas (1950-2019)

ABSTRACT Background & aim Bibliometric analysis is used to explore the historical development in a particular field. The aim is to identify and analyse most cited papers in benign anorectal disease in the last 7 decades (1950-2018). Method Thomson Reuters Web of Science database was used to find the top 100 cited articles in benign anorectal conditions. Papers were independently extracted by two investigators. The top 100 cited articles were identified and ranked according to number of citations. The articles were then sorted by author, journal, institution, country and publication date. The study subject was divided into 5 groups. Results The most frequently cited article received 1307 citations whereas the least cited received 154 citations. The earliest recorded article was published in 1960 and the most recent was from 2010. More than half of the articles addressed faecal incontinence and sphincter related literature (n = 54). The articles were published in 29 different journals. A majority (69%) of manuscripts originated from the USA (n = 35; 9221 citations) and UK (n = 34; 7796 citations). The origin of these top 100 classic papers was from 53 different institutions. St. Mark's Hospital in the UK had the highest number of articles (n = 21), followed by Cleveland clinic (n = 5) and University of Minnesota (n = 5). Conclusion The most highly cited manuscripts in benign anorectal disease cover a wide range of topics. Faecal incontinence and sphincter related articles had the highest number of citations. This review serves as a reference for researchers to find the influential papers in this field.

RESUMO Justificativa e objetivo A análise bibliométrica é usada para explorar o desenvolvimento histórico em um campo específico. O objetivo é identificar e analisar os artigos mais citados em doença anorretal benigna nas últimas 7 décadas (1950-2018). Método A base de dados Thomson Reuters Web of Science foi usada para encontrar os 100 artigos mais citados em doenças anorretais benignas. Os artigos foram extraídos de forma independente por dois pesquisadores. Os 100 artigos mais citados foram identificados e classificados de acordo com o número de citações. Os artigos foram classificados por autor, revista médica, instituição, país e data de publicação. Os sujeitos do estudo foram divididos em cinco grupos. Resultados O artigo mais citado recebeu 1.307 citações, enquanto o menos citado recebeu 154 citações. O artigo mais antigo foi publicado em 1960 e o mais recente a partir de 2010. Mais da metade dos artigos abordou a incontinência fecal e a literatura relacionada ao esfíncter (n = 54). Os artigos foram publicados em 29 revistas diferentes. A maioria (69%) dos manuscritos é originária dos EUA (n = 35; 9.221 citações) e do Reino Unido (n = 34; 7.796 citações). Os 100 artigos clássicos mais citados são originários de 53 instituições diferentes. O St. Mark's Hospital, no Reino Unido, teve o maior número de artigos (n = 21), seguido pela Clínica de Cleveland (n = 5) e pela Universidade de Minnesota (n = 5). Conclusão Os manuscritos mais citados em doença anorretal benigna abrangem uma grande variedade de tópicos. Os artigos relacionados à incontinência fecal e ao esfíncter tiveram o maior número de citações. Esta revisão serve de referência para os pesquisadores encontrarem os artigos influentes nesse campo.

Analysis of gene mutation associated with tyrosine kinase inhibitor sensitivity of epidermal growth factor receptor in cervical cancer patients.

OBJECTIVE: Cervical cancer is frequent in females. Epidermal growth factor receptor has a prominent expression in certain malignant tumors. This study aims to observe the expressional profile of epidermal growth factor receptor (EGFR) in cervical cancer patients, and mutation of EGFR gene related with its sensitivity towards tyrosine kinase inhibitor. MATERIALS AND METHODS: Cervical cancer patients from our hospital were recruited as the experimental group, in parallel with chronic cervicitis patients as control group. Serum EGFR level was measured by enzyme-linked immunosorbent assay (ELISA), and EGFR levels in cervical tissues were quantified by immunohistochemistry assay (IHC) staining. Real Time-PCR (RT-PCR) examined mutations of exon 18, 19, and 21 of the EGFR gene, to analyze their correlation with clinical or pathological features. RESULTS: Serum EGFR in experimental group was 1.16 ± 0.04 ng/ml, significantly higher than control group (p < 0.05). EGFR positive rate was 71.1% in cancer tissues, significantly higher compared to controlled or adjacent tissues (p < 0.05). Mutation rats of EGFR exon 19 and exon 21 were 3.3% and 5%, respectively. No mutation was found in exon 18. Such mutations of EGFR gene were related with cancer differentiation grade, tumor-lymph-node-metastasis (TNM) stage, lymph node or distal metastasis (p < 0.05), but not age, Karnofsky performance score (KPS) score or infiltration depth. CONCLUSIONS: EGFR is highly expressed in serum and tumors of cervical cancer patients, some of which showed mutations of exon 19 and 21 of EGFR gene with relatively lower frequency. Mutation rates were significantly higher in patients with highly differentiated grade, early TNM stage, and those without lymph node or distal metastasis.

Dunye Guanxinning Improves Acute Myocardial Ischemia-Reperfusion Injury by Inhibiting Neutrophil Infiltration and Caspase-1 Activity.

Acute myocardial infarction is the most serious manifestation of cardiovascular disease, and it is a life-threatening condition. Dunye Guanxinning (DG) is a protective traditional Chinese patent herbal medicine with high clinical efficacy and suitable for the treatment of myocardial infarction. However, the mechanism through which it is beneficial is unclear. In this study, we hypothesized that DG improves acute myocardial ischemia-reperfusion injury by inhibiting neutrophil infiltration and caspase-1 activity. We found that DG administration decreased infarct size and cardiomyocyte apoptosis and improved left ventricular ejection fraction, fractional shortening, end-systolic volume index, end-systolic diameter, and carotid arterial blood flow output in rats. DG administration also improved hemorheological parameters, myocardial damage biomarkers, and oxidative stress indexes. The findings showed that DG administration inhibited neutrophil infiltration and reduced the serum interleukin-1 beta (IL-1ß) level and myocardial IL-1ß maturation. Moreover, DG administration inhibited caspase-1 activity and activated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in rat hearts. These results suggested that DG administration inhibits inflammasome activity and IL-1ß release through the AMPK pathway. Our findings support the clinical efficacy of DG and partially reveal its mechanism, which is beneficial for understanding the therapeutic effects of this protective traditional Chinese patent drug.

Genetics of immune-mediated inflammatory diseases.

Immune-mediated inflammatory diseases (IMIDs) are characterized by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co-morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome-wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged. Understanding the genetic risk and extent of genetic overlap between IMIDs may help to determine which genes control which aspects of the different diseases; it may identify potential novel therapeutic targets for a number of these conditions, and/or it may facilitate repurposing existing therapies developed originally for different conditions. The findings show that autoantibody-mediated autoimmune diseases cluster more closely with each other than autoantibody-negative diseases such as psoriasis, psoriatic arthritis, Crohn's disease and ankylosing spondylitis which, instead, form a seronegative genetic cluster. The genetic clustering largely mirrors the known response to existing biological therapies, but apparent anomalies in treatment response are discussed.

KrasG12D-LOH promotes malignant biological behavior and energy metabolism of pancreatic ductal adenocarcinoma cells through the mTOR signaling pathway.

Oncogenic Kras with loss of heterozygosity (LOH) is frequently detected in various tumours. However, the exact function and mechanism by which KrasG12D-LOH operates remain unclear. Therefore, the current study investigated the effect of KrasG12D-LOH on the malignant phenotype of pancreatic ductal adenocarcinoma (PDAC) cells. Our investigation revealed that KrasG12D-LOH is associated with increased proliferation, invasion and reduced apoptosis in PDAC cells. The results also exhibited enhanced glycolytic phenotype of KrasG12D-LOH PDAC cells. Hyperactive mTOR plays a significant role in the initiation and maintenance of tumors. To investigate the correlation between KrasG12D-LOH and mTOR, the mTOR signaling pathway was detected by western blot analysis. We found that KrasG12D-LOH up-regulated Akt, AMPK, REDD1 and mTOR in PDAC cells. In summary, our results demonstrated that KrasG12D-LOH promotes oncogenic Kras-induced PDAC by regulating energy metabolism and mTOR signaling pathway. These data may provide novel therapeutic perspectives for PDAC.

Focal status epilepticus and progressive dyskinesia: A novel phenotype for glycine receptor antibody-mediated neurological disease in children.

BACKGROUND: Antibody-associated disorders of the central nervous system are increasingly recognised in adults and children. Some are known to be paraneoplastic, whereas in others an infective trigger is postulated. They include disorders associated with antibodies to N-methyl-d-aspartate receptor (NMDAR), voltage-gated potassium channel-complexes (VGKC-complex), GABAB receptor or glycine receptor (GlyR). With antibodies to NMDAR or VGKC-complexes, distinct clinical patterns are well characterised, but as more antibodies are discovered, the spectra of associated disorders are evolving. GlyR antibodies have been detected in patients with progressive encephalopathy with rigidity and myoclonus (PERM), or stiff man syndrome, both rare but disabling conditions. CASE REPORT: We report a case of a young child with focal seizures and progressive dyskinesia in whom GlyR antibodies were detected. Anticonvulsants and immunotherapy were effective in treating both the seizures and movement disorder with good neurological outcome and with a decline in the patient's serum GlyR-Ab titres. CONCLUSION: Glycine receptor antibodies are associated with focal status epilepticus and seizures, encephalopathy and progressive dyskinesia and should be evaluated in autoimmune encephalitis.

Expression and prognostic significance of microRNA-451 in human epithelial ovarian cancer.

OBJECTIVE: MicroRNA-451 has been proved to be downregulated in many human malignancies and correlated with tumor progression. However, its expression and clinical significance in epithelial ovarian cancer (EOC) is still unclear. The aim of this study was to explore the effects of miR-451 in EOC tumorigenesis and development. MATERIALS AND METHODS: The expression levels of miR-451 were quantified by qRT-PCR in 115 EOC and 34 normal ovarian tissues, and correlated with clinicopathological factors and prognosis. MTT, flow cytometric assay, and transwell invasion assay were used to test the proliferation, apoptosis, and invasion of SKOV-3 EOC cells transfected with miR-451 mimics or negative control (NC) RNA-oligonucleotides. RESULTS: MiR-451 expression was significantly downregulated in EOC compared with normal ovarian tissues. Low level of miR-451 was associated with advanced FIGO stage (p = 0.005), higher serum CA125 expression level (p = 0.005), and lymph node metastasis (p = 0.002). Multivariate Cox regression analysis identified decreased miR-451 expression as an independent factor predicting poor prognosis for EOC patients. In addition, transfection of miR-451 mimics in SKOV-3 was able to reduce cell proliferation, promote cell apoptosis, and inhibit cell invasion. CONCLUSIONS: miR-451 may act not only as a novel diagnostic and prognostic marker, but also as a potential target for molecular therapy of EOC.

Huntington's disease cerebrospinal fluid seeds aggregation of mutant huntingtin.

Huntington's disease (HD), a progressive neurodegenerative disease, is caused by an expanded CAG triplet repeat producing a mutant huntingtin protein (mHTT) with a polyglutamine-repeat expansion. Onset of symptoms in mutant huntingtin gene-carrying individuals remains unpredictable. We report that synthetic polyglutamine oligomers and cerebrospinal fluid (CSF) from BACHD transgenic rats and from human HD subjects can seed mutant huntingtin aggregation in a cell model and its cell lysate. Our studies demonstrate that seeding requires the mutant huntingtin template and may reflect an underlying prion-like protein propagation mechanism. Light and cryo-electron microscopy show that synthetic seeds nucleate and enhance mutant huntingtin aggregation. This seeding assay distinguishes HD subjects from healthy and non-HD dementia controls without overlap (blinded samples). Ultimately, this seeding property in HD patient CSF may form the basis of a molecular biomarker assay to monitor HD and evaluate therapies that target mHTT.

Decreased microRNA-206 and its function in cervical cancer.

OBJECTIVE: MicroRNA-206 plays important roles in tumorigenesis and tumor progression of various human malignancies. However, its involvement in cervical cancer has remained unclear. OBJECTIVE: The aim of this study was to examine the expression patterns and clinical implications of miR-206 in cervical cancer. MATERIALS AND METHODS: Quantitative RT-PCR was performed to evaluate the expression levels of miR-206 in cervical cancer cell lines and primary tumor tissues. The clinicopathologic significance and the prognostic value of miR-206 expression were further determined. Finally, the effects of miR-206 on HeLa cell proliferation, apoptosis, invasion, and migration were investigated. RESULTS: MiR-206 expression was significantly downregulated in cervical cancer samples when compared with normal adjacent tissues. Low level of miR-206 was associated with advanced FIGO stage (p < 0.001), positive lymph node metastasis (p < 0.001), poor differentiation (p = 0.016), and human papillomavirus infection (p = 0.007). Multivariate Cox regression analysis revealed that decreased miR-206 expression was an independent unfavorable prognostic factor for overall survival. In addition, transfection of miR-206 mimics in HeLa cells was able to reduce cell proliferation, promote cell apoptosis, and inhibit cell invasion and migration. CONCLUSIONS: miR-206 may act not only as a novel diagnostic and prognostic marker, but also as a potential target for molecular therapy of cervical cancer.

A causal role for circulating miR-34b in osteosarcoma.

PURPOSE: To investigate the associations between plasma miR-34b/c expression levels and osteosarcoma (OS). SUBJECTS AND METHODS: A case-control study was conducted in 133 patients with OS and 133 controls. MiR-34b/c levels were detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays. Genotyping of SNP rs4938723 was done using the TaqMan assay. The causal association was examined by mendelian randomization analysis. RESULTS: Plasma miR-34b level was significantly lower in OS patients than in controls (P = 0.001). Expression levels of miR-34b in OS tissues decreased (P = 3.22 × 10(-4)) and was significantly related with its expression in plasma (r = 0.21, P = 0.004). Compared with wild-type TT genotype, the variant genotypes of rs4938723 TC/CC were significantly associated with increased OS risk (TC vs. TT: OR, 1.97 [95% CI: 1.40-2.55], P = 0.021; CC vs. TT: OR, 2.76 [95% CI: 2.00-3.53], P = 0.009; TC + CC vs. TT: OR, 2.16 [95% CI: 1.61-2.70], P = 0.006), consistent with its decreased effect on plasma miR-34b (TC vs. TT: -0.32 (-0.43, -0.21), P < 0.001; CC vs. TT: -0.70 (-0.84, -0.56), P < 0.001; TC + CC vs. TT: -0.42 (-0.53, -0.32), P < 0.001). Adjustment for miR-34b completely abolished the association between SNP rs4938723 and OS risk (P > 0.05). In addition, plasma expression levels of miR-34b were significantly decreased in the metastatic patients compared with that in the non-metastatic ones (P = 0.004). CONCLUSION: Plasma miR-34b was causally associated with OS risk and related with its metastatic status, suggesting that plasma miR-34b might be a novel biomarker and a potential treatment target for OS.

Knock-down of USP22 by small interfering RNA interference inhibits HepG2 cell proliferation and induces cell cycle arrest.

The Ubiquitin--specific protease 22 (USP22) is a new putative cancer stem cell marker, which plays a significant role in tumorigenesis and cell--cycle progression. However, little is known about the impact of USP22 knock--down on the growth of human hepatoma cell lines. In this study, elevated expression of USP22 was observed in the human HepG2 hepatic cancer cell line compared to the normal human hepatocyte Chang liver cell line. Subsequently, we used siRNA specifically suppressing expression of USP22 and observed that the knock--down of USP22 could effectively induce cell cycle arrest and inhibit HepG2 cell proliferation. Furthermore, our results showed that USP22 deletion caused down--regulation of cyclin D2 expression and up--regulation of p15 and p21 expression. Collectively, Our findings indicate that USP22 may be responsible for HepG2 cell growth and USP22 regulates the cell cycle via the c--Myc/cyclin D2 pathway and down--regulating p15 and p21 expression in HepG2 cell.