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So far, the monoclonal hypothesis of tumor occurrence and development cannot be justified. The genetic diversity selection hypothesis for the occurrence and development of lung cancer links Mendelian genetics with Darwin's theory of evolution, suggesting that the genetic diversity of tumor cell populations with polyclonal origins-monoclonal selection-subclonal expansion is the result of selection pressure. Normal cells acquire mutations in oncogenic driver genes and have a selective advantage over other cells, becoming tumor initiating cells; In the interaction with the tumor microenvironment (TME), the vast majority of initiating cells are recognized and killed by the human immune system. If immune escape occurs, the incidence of malignant tumors will greatly increase, and subclonal expansion, intratumour heterogeneity, etc. will occur. This article proposed the hypothesis of genetic diversity selection and analyzed its clinical significance.
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Objective. Within the context of evidence-based practice, this article exposes the reflection on the understanding and usefulness of the information provided by the research findings shared in reports and research publications, exposing differences based on the interpretation of statistical significance and clinical significance. Content synthesis. Basic aspects of the meaning and use of the information reported by research on p value (statistical significance) and the value and usefulness of these results are analyzed and exemplified, contrasting the value for the practice of an additional judgment on clinical significance. In addition to establishing conceptual differences, the need is highlighted for nurses to have the competencies to differentiate and apply each of them according to the clinical contexts of their potential implementation. Conclusion. The real usefulness of research about interventions within the context of nursing care is given by its real application and reach for the practice and benefit for patients. For this to occur, nurses must interpret adequately the information provided by scientific publications and other research reports.

Objetivo. En el contexto de una práctica basada en evidencia, este artículo expone la reflexión sobre la comprensión y utilidad de la información que proveen los hallazgos de investigación reportados en informes y publicaciones de investigación, exponiendo las diferencias a partir de la interpretación de la significancia estadística y significancia clínica. Síntesis del contenido. Se analizan y ejemplifican aspectos básicos sobre el significado y uso de la información que reportan las investigaciones sobre valor p (significancia estadística) y el valor y utilidad de estos resultados contrastando el valor para la práctica de un juicio adicional sobre significancia clínica. Además de establecer diferencias conceptuales, se resalta la necesidad de que las enfermeras tengan las competencias para diferenciar y aplicar cada uno de ellos según los contextos clínicos de su potencial implementación. Conclusión. La real utilidad de la investigación sobre intervenciones en el contexto del cuidado de enfermería está dada por su real aplicación y alcance para la práctica y el beneficio para los pacientes. Para que ello ocurra, las enfermeras deben interpretar adecuadamente la información que proveen las publicaciones científicas y otros reportes de investigación.

Objetivo. No contexto de uma prática baseada em evidências, este artigo apresenta a reflexão sobre a compreensão e utilidade da informação fornecida pelos resultados da investigação relatados em relatórios de investigação e publicações, expondo as diferenças com base na interpretação da significância estatística e da significância clínica. Síntese de conteúdo. Aspectos básicos sobre o significado e uso das informações relatadas pelas pesquisas sobre valor p (significância estatística) e o valor e utilidade desses resultados são analisados e exemplificados, contrastando o valor para a prática de um julgamento adicional sobre significância clínica. Além de estabelecer diferenças conceituais, destaca-se a necessidade de o enfermeiro ter competências para diferenciar e aplicar cada uma delas de acordo com os contextos clínicos de seu potencial implementação. Conclusão. A real utilidade da investigação sobre intervenções no contexto dos cuidados de enfermagem é dada pela sua real aplicação e âmbito de prática e benefício para os pacientes. Para que isso ocorra, os enfermeiros devem interpretar adequadamente as informações fornecidas pelas publicações científicas e outros relatórios de pesquisa.

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Aim: To assess the research gaps identified in a recent mapping review of orthognathic surgery through their evaluation by clinical experts, leading to a clinically relevant list of research gaps. This will guide future investigations of the topic, focusing on the outcomes of blood loss, infection, and relapse. Methods: The Delphi technique will be used to appraise the identified research gaps. The expert panel will include maxillofacial surgeons who regularly perform orthognathic surgery. Potential participants will be identified through various methods, including contact information from articles in the mapping review, nominations from peers, and social media platforms. Two rounds of surveys will be undertaken with Likert-type and open-ended questions to assess the clinical relevance of research gaps. For the second round, participants will receive a report of the results of the first round. Questions will be modified depending on the answers obtained in the first round. A consensus of 60% will be considered valid. Conclusions: Through this Delphi study, in a collaborative effort between researchers and clinical experts, a comprehensive understanding of the clinical relevance of research gaps in orthognathic surgery will be achieved. The outcomes will guide future investigations, ultimately improving the outcomes and practices in this field.

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Introducción: desde el punto de vista anatómico, los adenomas hipofisarios (AH) se observan en el 10% de la población. Son en su mayoría pequeños y no funcionantes. La mayoría de los incidentalomas descubiertos en estudios de imágenes con alta resolución pedidos en situaciones clínicas frecuentes, como el traumatismo craneoencefálico, el accidente cerebrovascular y las demencias, corresponden a AH indolentes. Nos preguntamos cuál es la relevancia clínica de los adenomas hipofisarios. Desarrollo: los AH clínicamente relevantes son tumores en su mayoría benignos que conllevan, en diferentes proporciones, aumento en la morbilidad y/o mortalidad de los pacientes por mecanismos relacionados con la hipersecreción hormonal, la insuficiencia hormonal y/o los efectos de masa ocupante. La prevalencia de los AH clínicamente relevantes es mayor de la que se suponía hace 20 años. Afecta aproximadamente a 1/1000 habitantes. Los más prevalentes son los prolactinomas y los adenomas no funcionantes. La acromegalia, la enfermedad de Cushing y los tumores agresivos se traducen en pacientes complejos con mayor morbimortalidad. El diagnóstico temprano y el tratamiento multimodal proveen una razonable mejoría de la sobrevida. El estudio epidemiológico de los AH clínicamente relevantes es importante para la estimación del impacto en los sistemas de salud. Conclusiones: los estudios por imágenes de mejor resolución continuarán señalando incidentalomas hipofisarios. Una evaluación cuidadosa de los pacientes podrá identificar aquellos AH clínicamente relevantes. (AU)

Introduction: from the anatomical point of view, pituitary adenomas (HA) are observed in 10% of the population. They are mostly small and non-functioning. Most incidentalomas discovered in high-resolution imaging studies ordered in frequent clinical situations, such as head trauma, stroke and dementia, correspond to indolent HA. We wonder what is the clinical relevance of pituitary adenomas. Development: clinically relevant HAs are mostly benign tumors that lead, in different degrees, to an increased morbidity and/or mortality in patients by mechanisms related to hormone hypersecretion, hormone insufficiency and/or occupying mass effects. The prevalence of clinically relevant HA is higher from what was assumed 20 years ago. It affects approximately 1/1000 of the population. The most prevalent are prolactinomas and non-functioning adenomas. Acromegaly, Cushing's disease and aggressive tumors make for complex patients with increased morbidity and mortality. Early diagnosis and multimodal treatment provide a reasonable improvement in survival. Epidemiological study of clinically relevant HAs is important for estimating the impact on health systems. Conclusions: Higher-resolution imaging studies will continue to highlight pituitary incidentalomas. Careful evaluation of patients will identify clinically relevant HAs. (AU)

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Objective: To investigate the clinical significance of pathological diagnosis and genetic abnormalities detection of gastrointestinal stromal tumor (GIST) using endoscopic biopsy. Methods: Patients with GIST diagnosed by endoscopic biopsy (from January 1st, 2016 to August 1st, 2018, at Zhongshan Hospital, Fudan University) were included in this study. This retrospective study evaluated the histopathologic and immunohistochemical (IHC) features, genetic abnormalities of the tumors and the treatment and clinical course of the patients. Results: Totally 4 095 cases of GIST were collected, among which 67 patients (67/4 095, 1.6%) underwent endoscopic biopsy. Forty-eight patients (71.6%) were male and 19 (28.4%) were female, with a mean age of 61 years (range 31-90 years). Fifty-nine lesions were located in stomach and eight in duodenum. Of all the 67 cases, 47 were spindle type, 14 were epithelioid type, and 6 mixed type. IHC staining showed the positive rates were 100.0% (64/64) for DOG1, 98.4% (62/63) for CD117, 87.5% (56/64) for CD34, 3.6% (2/56) for S-100 protein, 12.1% (7/58) for α-SMA, 12.3% (7/57) for desmin and 4.0% (2/50) for CKpan. Morphologically, 34 cases were malignant; three cases (all epithelioid type) were originally misdiagnosed as poorly differentiated carcinoma; missed-diagnosis were found in four cases (spindle type) due to the insufficient diagnostic tumor cells. The genetic abnormality detection rate in the biopsy tissue was 38.8% (26/67),among them two patients were lost to follow up after biopsy, 33 patients received surgical resection, 16 cases underwent operation after neoadjuvant therapy and 16 patients with advanced disease underwent continuous imatinib therapy, with the genetic testing rate of 6.1% (2/33), 10/16 and 14/16, respectively. Conclusions: Endoscopic biopsy is a useful but rare method for the preoperative diagnosis of GIST. For majority of biopsy, accurate pathological diagnosis and auxiliary examination can be completed to guide clinical treatment. A thorough history in combination with endoscopic finding is essential to avoid misdiagnosis (epithelioid type) and missed diagnosis (spindle type) in suspicious cases. Genetic testing should be recommended in patients who will undergo targeted therapy after endoscopic biopsy, and it can provide valuable information and guidance for clinical treatment.

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Axillary arch is the most common type of axillary muscle fiber variation, with about 10.8% incidence in the Chinese population. Its natural forms are varied and fluid, with different starting points and terminations, and clinicians frequently lack recognition. Under commonly applicated sentinel lymph node biopsy, the axillary arch has been endowed with more clinical significance. The fabric of axillary arch will not only block lymphatic drainage in axilla and unclear anatomical level of axillary dissection, but also compress the axillary neurovascular bundle, causing upper limb venous thrombosis, lymphedema and nerve entrapment. The intumescent axillary arch may also show abnormal axillary bulge. In addition to finding axillary arch during cadaveric study and operation, several of imaging methods availably diagnose axillary arch preoperative, which can create new way for detection of axillary arch and extension of the surgical plan of sentinel lymph node biopsy. Although embryology and comparative anatomy have been used to explain the origin of the axillary arch, most of the ideas are still hypotheses and need further study.

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OBJECTIVES@#To study the expression of interleukin-17A (IL-17A) in the serum of children with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) and its clinical significance.@*METHODS@#A total of 143 children with KD who were hospitalized in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from June 2021 to June 2022 were enrolled in this prospective study, among whom 115 had IVIG-sensitive KD and 28 had IVIG-resistant KD. After matching for sex and age, 110 children with acute respiratory infectious diseases (fever time ≥5 days but without KD) were enrolled as the control group. The enzyme-linked immunosorbent assay was used to measure the serum level of IL-17A. The levels of white blood cell count (WBC), neutrophil count (NE), platelet count, erythrocyte sedimentation rate, and C-reactive protein (CRP) were measured. The receiver operating characteristic curve was plotted to analyze the value of WBC, NE, CRP, and IL-17A in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis was used to evaluate the predictive factors for resistance to IVIG in children with KD.@*RESULTS@#Before IVIG treatment, the KD group had a significantly higher serum level of IL-17A than the control group (P<0.05), and the children with IVIG-resistant KD had a significantly higher serum level of IL-17A than those with IVIG-sensitive KD (P<0.05). The receiver operating characteristic curve analysis showed that WBC, NE, CRP, and IL-17A had an area under the curve of 0.718, 0.741, 0.627, and 0.840, respectively, in the prediction of IVIG-resistant KD. With serum IL-17A ≥44.06 pg/mL as the cut-off value, IL-17A had a sensitivity of 84% and a specificity of 81% in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis showed that a high serum level of IL-17A was a predictive factor for resistance to IVIG in children with KD (OR=1.161, P=0.001).@*CONCLUSIONS@#Serum IL-17A levels are elevated in children with IVIG-resistant KD, and serum IL-17A level (≥44.06 pg/mL) may have a predictive value for resistance to IVIG in children with KD.

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OBJECTIVE@#To investigate the cytokine/chemokine profile in patients with Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH), and assess the prognostic value of survival.@*METHODS@#Serum levels of thirty-eight cytokines/chemokines were measured by multiple cytokine assay kit in EBV-related HLH patients, EBV-infected patients, and controls. The expression profile of cytokines/chemokines was compared among groups. The changes of cytokine/chemokine expression in active and remission stage of EBV-related HLH patients were also compared, and the prognostic values for survival were evaluated.@*RESULTS@#Serum levels of interferon-α2 (IFN-α2), interleukin (IL)-6, and IL-7 in EBV-related HLH patients were 33.67(23.23-68.78) pg/ml, (74.95±25.53) pg/ml, and 35.35(19.50-63.55) pg/ml, respectively, which were significantly higher than those in EBV-infected patients［IFN-α2: 16.07(9.87-29.63); IL-6: 55.91±20.29; IL-7: 20.40(13.35-31.40)］ and controls ［IFN-α2: 11.02(4.67-21.25); IL-6:42.64±13.41; IL-7: 16.95(14.95-33.78)］(all P<0.05). Serum levels of IL-8, IL-9, and marcophage-derived chemokine (MDC) in EBV-related HLH patients were 11.00(7.50-15.27) pg/ml, 81.30(40.79-111.0) pg/ml, and (512.6±128.7) pg/ml, respectively, which were significantly higher than those in controls ［IL-8: 6.80(5.56-8.38); IL-9: 41.30(29.82-67.91); MDC: 384.1±156.6］(all P<0.05), but there was no remarkable differences compared with EBV-infected patients (P>0.05). Serum IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC in survival and death groups of EBV-related HLH patients were analyzed by receiver operating characteristic curve with area under curve of 0.781, 0.778, 0.633, 0.805, 0.562, and 0.657, respectively (P=0.019, 0.021, 0.269, 0.015, 0.607, and 0.190). IFN-α2, IL-6, and IL-8 had good predictive effect on survival. Serum level of IFN-α2, IL-6, and MDC of EBV-related HLH patients in remission stage were significantly lower than those in active stage (P<0.05), while IL-7, IL-8, and IL-9 were not different (P>0.05).@*CONCLUSION@#IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC may take part in the pathogenesis of EBV-related HLH.

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Colorectal cancer is one of the most common cancers in the world, and surgery is the mainstage treatment. Urogenital and sexual dysfunction after radical resection of rectal cancer has become an important problem for patients, which seriously affects the quality of life. Some patients give up radical surgery for rectal cancer because of the concerns about sexual and urinary dysfunction. The cause of this problem is intraoperative of injury pelvic autonomic nerve. The preservation of the hypogastric nerve during the surgery is important for the male ejaculation. Pelvic splanchnic nerves are mainly responsible for the male erection. The anatomical origin, distribution, and urogenital function of these two nerves are detailed described in this article. At the same time, this article introduces the classification, key points of the operation and the evaluation of autonomic nerve preservation surgery. With the rapid development of minimally invasive surgery, performing radical surgery for rectal cancer is important, we also need to fully understand the anatomical concept of pelvic autonomic nerves, and apply modern minimally invasive surgical techniques to preserve the patient's pelvic autonomic nerves as well. It is an compulsory course and an important manifestation for the standardization of rectal cancer surgery.

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Objective: To investigate the relationship between the long-non-coding RNA LINC00342 expression and the clinicopathological parameters of head and neck squamous cell carcinoma (HNSCC) and the biological function of LINC00342 in HNSCC cells. Methods: The expression level of LINC00342 in the HNSCC was analyzed using transcriptome sequencing data from TCGA (The Cancer Genome Atlas) database, and the expressions of LINC00342 in laryngeal squamous cell carcinoma tissues (LSCC) of 27 patients in the First Hospital of Shanxi Medical University were detected by transcriptome sequencing. The expression levels of LINC00342 in human embryonic lung diploid cells 2BS, HNSCC cell lines FD-LSC-1, CAL-27 and Detroit562 were determined by real-time quantitative polymerase chain reaction (qPCR). RNAi (RNA interference) was used for LINC00342 knockdown in HNSCC cell lines, and the changes of malignant phenotype in the tumor cells after LINC00342 knockdown were examined by cell counting kit-8 (CCK-8), colony formation, flow cytometry, transwell invasion and migration assays. Bioinformatics analysis was performed to construct a LINC00342-centered competing endogenous RNA (ceRNA) regulatory network, and GO (Gene Ontology) enrichment analysis was performed. Statistical analysis and graphing were performed using SPSS 25.0 software and GraphPad Prism 6 software. Results: Mean LINC00342 levels in HNSCC tissues and TCGA database were higher than that in normal control tissues, but with no significantly statistical difference (P=0.522). LINC00342 expression levels were positively correlated with cervical lymph node metastasis and pathological grade in patients with HNSCC, with higher expression in male patients than in female patients (P<0.05). Transcriptome sequencing analysis showed that mean expression level of LINC00342 in LSCC tissues of 27 patients was significantly higher than that in the paired adjacent normal mucosa tissues (t=1.56, P=0.036). LINC00342 expression was significantly upregulated in HNSCC cell lines FD-LSC-1, CAL-27 and Detroit562 (t-values of -12.17, -23.26 and -388.57, respectively; all P<0.001). Knockdown of LINC00342 by transfecting si-LINC00342-1 and si-LINC00342-2 inhibited HNSCC cell proliferation (t-values of 8.95 and 4.84, 2.70 and 5.55, 2.02 and 3.70, respectively), colony formation (t-values of 6.66 and 6.17, 7.38 and 11.65, 4.90 and 5.79, respectively), migration (t-values of 8.21 and 7.19, 5.76 and 6.46, 6.28 and 9.92, respectively) and invasion abilities (t-values of 9.29 and 10.25, 11.30 and 11.36, 8.02 and 8.66, respectively), but promoting apoptosis in cell lines FD-LSC-1 and CAL-27 (t-values of -2.21 and -5.83, -3.05 and -5.25 respectively) (all P-values<0.05). The LINC00342-centered ceRNA network consists of 10 downregulated microRNA and 647 upregulated mRNA nodes. GO analysis results indicated that LINC00342-regulated mRNAs were enriched in 22 biological processes, 32 molecular functions, and 12 cellular components. Conclusion: High level of LINC00342 is associated with the malignant progression of HNSCC. LINC00342 promotes the proliferation, migration, invasion, and antagonizes apoptosis of HNSCC cells, which serves as a potential molecular marker in HNSCC.

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Virtually all of the dietary potassium intake is absorbed in the intestine, over 90% of which is excreted by the kidneys regarded as the most important organ of potassium excretion in the body. The renal excretion of potassium results primarily from the secretion of potassium by the principal cells in the aldosterone-sensitive distal nephron (ASDN), which is coupled to the reabsorption of Na+ by the epithelial Na+ channel (ENaC) located at the apical membrane of principal cells. When Na+ is transferred from the lumen into the cell by ENaC, the negativity in the lumen is relatively increased. K+ efflux, H+ efflux, and Cl- influx are the 3 pathways that respond to Na+ influx, that is, all these 3 pathways are coupled to Na+ influx. In general, Na+ influx is equal to the sum of K+ efflux, H+ efflux, and Cl- influx. Therefore, any alteration in Na+ influx, H+ efflux, or Cl- influx can affect K+ efflux, thereby affecting the renal K+ excretion. Firstly, Na+ influx is affected by the expression level of ENaC, which is mainly regulated by the aldosterone-mineralocorticoid receptor (MR) pathway. ENaC gain-of-function mutations (Liddle syndrome, also known as pseudohyperaldosteronism), MR gain-of-function mutations (Geller syndrome), increased aldosterone levels (primary/secondary hyperaldosteronism), and increased cortisol (Cushing syndrome) or deoxycorticosterone (hypercortisolism) which also activate MR, can lead to up-regulation of ENaC expression, and increased Na+ reabsorption, K+ excretion, as well as H+ excretion, clinically manifested as hypertension, hypokalemia and alkalosis. Conversely, ENaC inactivating mutations (pseudohypoaldosteronism type 1b), MR inactivating mutations (pseudohypoaldosteronism type 1a), or decreased aldosterone levels (hypoaldosteronism) can cause decreased reabsorption of Na+ and decreased excretion of both K+ and H+, clinically manifested as hypotension, hyperkalemia, and acidosis. The ENaC inhibitors amiloride and Triamterene can cause manifestations resembling pseudohypoaldosteronism type 1b; MR antagonist spironolactone causes manifestations similar to pseudohypoaldosteronism type 1a. Secondly, Na+ influx is regulated by the distal delivery of water and sodium. Therefore, when loss-of-function mutations in Na+-K+-2Cl- cotransporter (NKCC) expressed in the thick ascending limb of the loop and in Na+-Cl- cotransporter (NCC) expressed in the distal convoluted tubule (Bartter syndrome and Gitelman syndrome, respectively) occur, the distal delivery of water and sodium increases, followed by an increase in the reabsorption of Na+ by ENaC at the collecting duct, as well as increased excretion of K+ and H+, clinically manifested as hypokalemia and alkalosis. Loop diuretics acting as NKCC inhibitors and thiazide diuretics acting as NCC inhibitors can cause manifestations resembling Bartter syndrome and Gitelman syndrome, respectively. Conversely, when the distal delivery of water and sodium is reduced (e.g., Gordon syndrome, also known as pseudohypoaldosteronism type 2), it is manifested as hypertension, hyperkalemia, and acidosis. Finally, when the distal delivery of non-chloride anions increases (e.g., proximal renal tubular acidosis and congenital chloride-losing diarrhea), the influx of Cl- in the collecting duct decreases; or when the excretion of hydrogen ions by collecting duct intercalated cells is impaired (e.g., distal renal tubular acidosis), the efflux of H+ decreases. Both above conditions can lead to increased K+ secretion and hypokalemia. In this review, we focus on the regulatory mechanisms of renal potassium excretion and the corresponding diseases arising from dysregulation.

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Early life nutritional environment is not only associated with the growth and development of children, but also affects the health of adults. Numerous epidemiological and animal studies suggest that early nutritional programming is an important physiological and pathological mechanism. DNA methylation is one of the important mechanisms of nutritional programming, which is catalyzed by DNA methyltransferase, a specific base of DNA covalently binds to a methyl group, to regulate gene expression. In this review, we summarize the role of DNA methylation in the "abnormal developmental planning" of key metabolic organs caused by excessive nutrition in early life, resulting in long-term obesity and metabolic disorders in the offspring, and explore the clinical significance of regulating DNA methylation levels through dietary interventions to prevent or reverse the occurrence of metabolic disorders in the early stage in a "deprogramming" manner.

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Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.

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OBJECTIVE@#To detect the relative expression of IGLL1 (immunoglobulin lambda-like polypeptide 1) mRNA in bone marrow of children with T-cell acute lymphoblastic leukemia (T-ALL), and analyze its correlation with the clinical characteristics and prognosis of the patients, so as to clarify the clinical significance of IGLL1 in pediatric T-ALL patients.@*METHODS@#A total of 56 pediatric T-ALL patients hospitalized in Children's Hospital of Soochow University from June 2012 to December 2017 and treated with CCLG-ALL 2008 regimen were selected. Transcriptome sequencing technology was used to detect the transcription level of IGLL1 gene in children with T-ALL. According to 25% of the IGLL1 transcription level (cutoff value:448), the enrolled children were divided into IGLL1 low expression group (17 cases) and IGLL1 high expression group (39 cases). Combined with clinical data, the correlation between the expression level of IGLL1 and prognosis of the patients was analyzed.@*RESULTS@#The comparative analysis showed that the transcription level of IGLL1 was not correlated with the clinical characteristics of the patients, such as sex, age, bone marrow blast, white blood cell (WBC) count at initial diagnosis. The 5-year OS rate of patients with high IGLL1 expression was significantly higher than that of patients with low IGLL1 expression (76.9%±6.7% vs 47.1%±12.1%, P =0.018). Further comparison of relapse-free survival (RFS) rate between the two groups showed that the 5-year RFS rate of patients with high IGLL1 expression was higher than that of patients with low IGLL1 expression, but the difference between the two groups was not statistically significant (P =0.095). Multivariate COX analysis was conducted on common clinical prognostic factors (age, sex, WBC count at diagnosis, prednisone response on the 7th day, bone marrow response on the 15th day after treatment) and IGLL1 expression level, and the results showed that IGLL1 expression (P =0.012) and prednisone response (P =0.017) were independent risk factors for overall survival in pediatric T-ALL patients.@*CONCLUSION@#In pediatric T-ALL, the OS rate of children with high expression of IGLL1 gene was significantly higher than that of children with low expression of IGLL1 gene, and the expression level of IGLL1 gene was an independent factor affecting the survival of children with T-ALL, which suggests that IGLL1 is a marker of good clinical prognosis of children with T-ALL.

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OBJECTIVE@#To explore the consistency of flow cytometry (FCM) method and polymerase chain reaction (PCR) technique in the detection of minimal residual disease (MRD) at different treatment stages in pediatric patients with TCF3/PBX1+ B-cell acute lymphoblastic leukemia (B-ALL) and the correlations between the detection results and prognosis.@*METHODS@#The clinical data of 64 newly diagnosed pediatric patients with TCF3/PBX1+ B-ALL admitted to the Department of Pediatrics of Peking University People's Hospital from January 2005 to December 2017 were retrospectively analyzed. FCM and PCR methods were used to monitor the MRD level in bone marrow samples from 64 children during the same period of treatment on d33 and d90 respectively, and the detection results were analyzed.@*RESULTS@#There were 37 males and 27 females in the 64 patients, with a median age of 8 years(range 0.8 to 16 years). The complete remission (CR) rate after the first cycle of induction chemotherapy was 98.4% (62/63), with overall CR rate of 100%. 12 patients experienced recurrence, with a median recurrence time of 16.9 (5.3-46.3) months. The median follow-up time of the 64 patients was 77.2 (1.0-184.8) months , and the 5-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±4.7% and 75.0%±5.4%, respectively. On d90, the concordance rate of the MRD results from the two methods was 98.4%, and the related kappa value was 0.792 (P < 0.001), which were significantly higher than those on d33. After induction chemotherapy (d33), the 5-year EFS rate of MRD-FCM- group (79.3%±5.3%) was significantly better than that of MRD-FCM+ group (40.0%±21.9%) (P =0.028), there were no significant differences in the 5-year OS rate and EFS rate between MRD-PCR+ group and MRD-PCR- group, and the 5-year EFS rate of MRD-FCM-/PCR- group (85.4%±5.5%) was significantly better than that of MRD-FCM+/PCR+ group (40.0 %±21.9%) (P =0.026).@*CONCLUSION@#In children with TCF3/PBX1+ B-ALL, the MRD results detected by FCM and PCR methods show good consistency, especially in consolidation therapy period (d90). The MRD level at the end of induction therapy (d33) is an important factor affecting the long-term prognosis, especially the MRD results detected by FCM method, which is significantly associated with prognosis.

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OBJECTIVE@#To investigate the expression and clinical significance of T helper cell 9 (Th9) and its cytokine interleukin 9(IL-9) in peripheral blood of patients with chronic lymphocytic leukemia(CLL).@*METHODS@#A total of 43 newly diagnosed patients with chronic lymphocytic leukemia in the First Affiliated Hospital of Xinjiang Medical University from June 2021 to June 2022 were selected as the case group. The patients were divided into Binet A group (13 cases), Binet B group (20 cases) and Binet C group (10 cases) by Binet staging system, and 20 healthy volunteers who underwent physical examinationin in our hospital in the same period served as control group. The proportion of Th9 cells in peripheral blood was detected by flow cytometry, the expression level of Th9 specific transcription factors PU.1 and IRF4 was detected by Western blot, and the expression level of serum cytokine IL-9 was detected by ELISA. The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in each group were compared, and the correlation between the proportion of Th9, IL-9 and clinicopathological indexes of CLL patients was analyzed.@*RESULTS@#The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in CLL group were significantly higher than those in control group (P<0.05), the proportion of Th9 and the expression of IL-9 in Binet B and C group were higher than those in Binet A group (P<0.05), but there was no significant difference in the proportion of Th9 cells between Binet B group and C group (P>0.05). The expression of IL-9 in Binet C group was significantly higher than that in Binet B group (P<0.05) . The proportion of Th9 cells and IL-9 were highly expression in patients with β2 microglobulin abnormality, IGHV unmutation, P53 abnormality and hepatosplenic lymph node enlargement(P<0.05), but not related to age and sex (P>0.05). The results of Spearman correlation analysis showed that the proportion of Th9 in patients with CLL was negatively correlated with the lymphocytic account and lymphocyte proportion(rs=-0.32，rs=-0.34). The proportion of Th9 and IL-9 were positively correlated with Binet stage, Rai stage and CLL-IPI Scoring (rs=0.79，rs=0.54，rs=0.58； rs=0.72，rs=0.63，rs=0.45), but not with WBC, CD4+ T cells and CD8+T cells (P>0.05). The proportion of Th9 was positively correlated with IL-9 (rs=0.53).@*CONCLUSION@#Th9 cells and IL-9 are abnormally highly expressed in CLL, which is related to the poor prognosis of CLL.

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OBJECTIVE@#To explore the expression of Exosome Component 4（EXOSC4） in the tissues of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance.@*METHODS@#The expression of EXOSC4 protein in the tissues of 181 newly diagnosed DLBCL patients was analyzed by immunohistochemical staining. Clinical data were collected. The correlation between EXOSC4 protein expression in the tissues of newly diagnosed DLBCL patients and clinical features were analyzed and its prognostic significance.@*RESULTS@#The positive rate of EXOSC4 protein expression was 68.51% in the tissues of 181 newly diagnosed DLBCL patients. These patients were divided into two groups, with 44 cases in high expression group and 137 cases in low expression group. There were no significant differences in age, gender, B symptoms, serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) score, Ann Arbor stage, extranodal disease, International Prognostic Index (IPI) score, National Comprehensive Cancer Network IPI (NCCN-IPI) score, and cell origin between the two groups (P>0.05). Cox multivariate regression analysis showed that high EXOSC4 protein expression in tissues was an independent poor prognostic factor for OS and PFS in newly diagnosed DLBCL patients (all P<0.05). K-M survival analysis showed that newly diagnosed DLBCL patients with high EXOSC4 protein expression had significantly shorter overall survival (OS) and progression free survival (PFS) than those patients with low EXOSC4 protein expression (all P<0.05).@*CONCLUSION@#High EXOSC4 protein expression in tissues of newly diagnosed DLBCL patients is an independent poor prognostic factor for survival.

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OBJECTIVE@#To observe the levels of soluble programmed cell death protein 1 (sPD-1) and soluble programmed cell death ligand 1 (sPD-L1) in peripheral blood of lymphoma patients, and reveal their clinical significances.@*METHODS@#The peripheral blood specimens and clinical data of 64 newly diagnosed lymphoma patients and 30 healthy volunteers were collected. The levels of sPD-1 and sPD-L1 were detected by enzyme-linked immunosorbent assay (ELISA), and their correlations with clinical characteristics of the patients including pathological type, stage, lactate dehydrogenase (LDH) level, T cell subsets were analyzed.@*RESULTS@#The levels of both sPD-1 and sPD-L1 in peripheral blood of lymphoma patients were higher than those of normal controls (P <0.05). There were no significant differences in sPD-1 and sPD-L1 levels in peripheral blood between Hodgkin lymphoma and non-Hodgkin lymphoma patients. Different pathological subtypes of lymphoma had different levels of sPD-1. The level of sPD-1 in patients with T-cell lymphoma was higher than that in patients with B-cell lymphoma (P =0.001). The levels of both sPD-1 and sPD-L1 in patients with Ann Arbor stage III and IV were higher than those in patients with stage I and II (P <0.05). The level of sPD-L1 in patients with abnormally increased LDH was higher than that in patients with normal LDH (P =0.001), but there was no significant difference in sPD-1 level. T cell subset analysis showed that the level of sPD-L1 was negatively correlated to CD4+ T cell content (r =-0.265).@*CONCLUSION@#The levels of sPD-1 and sPD-L1 in peripheral blood of lymphoma patients are related to the pathological type, Ann Arbor stage, LDH content and T cell subsets, and will be potential biomarkers in predicting the prognosis of lymphoma.

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OBJECTIVE@#To study the expression level of nicotinamide phosphoribosyltransferase (NAMPT) in multiple myeloma (MM), its relationship with clinical indicators, prognosis and potential role.@*METHODS@#Immunohistochemical staining was used to detect the expression of NAMPT in bone marrow biopsies of patients with newly diagnosed multiple myeloma (NDMM) and patients with iron deficiency anemia (IDA) hospitalized during the same period. According to the median expression level of NAMPT, NDMM patients were divided into high expression group and low expression group. The correlation between NAMPT expression level and clinical baseline data was analyzed, and survival analysis was performed to evaluate the relationship between NAMPT expression level and prognosis. The GSE24080 and GSE19784 datasets were used to analyze the effect of NAMPT on the prognosis. Gene set enrichment analysis (GSEA) explored the possible mechanism of NAMPT involved in MM cell function.@*RESULTS@#The mean staining intensity of NAMPT in bone marrow tissue of 31 NDMM patients was 0.007±0.002, and that of 10 IDA patients was 0.002±0.002 (P < 0.05). The median expression level of NAMPT was 0.0041 in NDMM patients, and the mean staining intensity of high expression group and low expression group was 0.007±0.005 and 0.002±0.001, respectively (P < 0.001). There were certain differences in lactate dehydrogenase (LDH), C-reactive protein (CRP) and ISS staging between high expression group and low expression group (P < 0.001), while no significant differences in other indicators. The overall response rate (ORR) of high expression group was significantly lower than that of low expression group (P < 0.001). The median survival time of patients in high expression group was significantly shorter than that in low expression group (P =0.024). The results of bioinformatics analysis showed that the event-free survival (EFS) rate and overall survival (OS) rate of low NAMPT group were both higher than high NAMPT group (P =0.037, P =0.009), and NAMPT was an independent prognostic factor for EFS and OS (P =0.006, P =0.020). GSEA suggested that NAMPT might affect MM cell function through mTORC1 signaling pathway.@*CONCLUSIONS@#The expression level of NAMPT in bone marrow of NDMM patients is significantly higher than that of IDA patients, and the high expression of NAMPT may be correlated with late ISS stage, and high level of LDH and CRP. Patients with high expression of NAMPT have worse response to bortezomib and survival time may be shorter. NAMPT may be involved in the occurrence and development of MM through mTORC1 signaling pathway.

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BACKGROUND@#Human neutrophil lipocalin (HNL) has been used extensively to differentiate acute bacterial infection from febrile diseases as a biomarker to reflect the activation of the neutrophil. The serum HNL levels in the adult-onset Still's disease (AOSD) patients with and without infection, as well as the healthy controls (HCs), were analyzed statistically in this study to evaluate the value of HNL for the diagnosis of AOSD.@*METHODS@#A total of 129 AOSD patients were enrolled, from whom blood samples were drawn and the AOSD diagnosis was confirmed through the review of the medical records, where the systemic score, demographic characteristics, clinical manifestations, and laboratory parameters were also collected for the patients; in addition, a total of 40 HCs were recruited among the blood donors from the healthcare center with the relevant information collected. The HNL test was done for the blood samples with the enzyme-linked immunosorbent assay and the analyses were done for the correlations of HNL with clinical manifestations and diagnostic effectiveness.@*RESULTS@#The serum HNL increased significantly in the patients with only AOSD as compared with that in the HCs (139.76 ± 8.99 ng/mL vs . 55.92 ± 6.12 ng/mL; P  < 0.001). The serum HNL level was correlated with the white blood cell (WBC) count ( r  = 0.335, P  < 0.001), neutrophil count ( r  = 0.334, P  < 0.001), erythrocyte sedimentation rate ( r  = 0.241, P  = 0.022), C-reactive protein ( r  = 0.442, P  < 0.0001), and systemic score ( r  = 0.343, P  < 0.0001) in the AOSD patients significantly. Patients with fever, leukocytosis ≥15,000/mm 3 , and myalgia in the HNL-positive group were observed relatively more than those in the HNL-negative group ( P  = 0.009, P  = 0.023, and P  = 0.007, respectively). HNL was a more sensitive indicator than ferritin and C-reactive protein (CRP) to differentiate the AOSD patients with bacterial infection from AOSD-only patients, and the Youden index was 0.6 for HNL and 0.29 for CRP.@*CONCLUSION@#Serum HNL can be used as a biomarker for the diagnosis of the AOSD, and HNL is also observed to be associated with the disease activity.