Objective:To explore the application of metagenomic next-generation sequencing (mNGS) in critically ill children with hematological disorders and evaluate its diagnostic value.Methods:A retrospective analysis was conducted on the clinical data of children with hematological diseases, tumors, and hematopoietic stem cell transplantation who underwent traditional culture and mNGS testing in the pediatric intensive care unit of the Xiangya Hospital, Central South University from September 2019 to June 2022. The detection rate and diagnostic value of traditional culture and mNGS for pathogens were analyzed and compared.Results:Among the 50 patients, there were 29 males and 21 females, with a median age of 9.00(4.75-13.00) years. A total of 60 samples were sent for mNGS testing, including 40 blood samples, 10 bronchoalveolar lavage fluid samples, 7 cerebrospinal fluid samples, and 1 bone marrow, 1 skin, and 1 pleural fluid sample each. 49 positive samples were detected by mNGS, including 20 cases of viruses, 14 cases of bacteria, 8 cases of mixed samples, and 7 cases of fungi. The detection rate of mNGS in this study was significantly higher than that in traditional pathogen culture (81.7% vs 16.7%), and the difference was statistically significant ( P<0.01). Based on clinical diagnostic cases, the sensitivity of mNGS was significantly higher than that of traditional culture (85.2% vs 29.6%), with a statistically significant difference ( P<0.01), while its specificity was not statistically significant ( P>0.05) compared to traditional culture (50.0% vs 83.3%). Conclusions:mNGS has a higher detection rate and sensitivity than traditional pathogen culture, and can early identify viral, fungal, and mixed infections, providing strong assistance for precise treatment of critically ill children with hematological conditions.

Objective:To summarize the best evidence for external auditory canal irrigation in patients with cerumen embolism.Methods:The clinical decisions, guidelines, systematic reviews, expert consensus, group standards, evidence summaries, and randomized controlled trials regarding external auditory canal irrigation in patients with cerumen embolism were retrieved from databases and websites such as BMJ Best Practice, UpToDate, Guidelines International Network, National Institute for Health and Clinical Excellence, Joanna Briggs Institute Evidence-Based Health Care Center Database, PubMed, Embase, China National Knowledge Infrastructure, WanFang data, and China Biology Medicine disc. The search period was from database establishment to February 15, 2023. Six researchers screened the literature, evaluated the methodological quality, and extracted and summarized the best evidence for external auditory canal irrigation in patients with cerumen embolism.Results:A total of nine articles were included, including one clinical decision, two guidelines, two systematic reviews, one group standard, and three randomized controlled trials. Sixteen pieces of evidence were summarized from six aspects of operators: pre-operation evaluation and preparation, operation process, post-operation handling, health education, and adverse reactions during operation.Conclusions:This paper summarizes the best evidence for external auditory canal irrigation in patients with cerumen embolism. Medical and nursing staff should carefully select and apply evidence based on clinical scenarios and patient's wishes.

More than 100 genes located on the X chromosome have been found to be associated with X-linked intellectual disability (XLID) to date, and NEXMIF is a pathogenic gene for XLID. In addition to intellectual disability, patients with NEXMIF gene mutation can also have other neurological symptoms, such as epilepsy, abnormal behavior, and hypotonia, as well as abnormalities of other systems. Two children with intellectual disability and epilepsy caused by NEXMIF gene mutation were treated in the Department of Pediatrics, Xiangya Hospital, Central South University from March 8, 2017 to June 20, 2020. Patient 1, a 7 years and 8 months old girl, visited our department because of the delayed psychomotor development. Physical examination revealed strabismus (right eye), hyperactivity, and loss of concentration. Intelligence test showed a developmental quotient of 43.6. Electroencephalogram showed abnormal discharge, and cranial imaging appeared normal. Whole exome sequencing revealed a de novo heterozygous mutation, c.2189delC (p.S730Lfs*17) in the NEXMIF gene (NM_001008537). During the follow-up period, the patient developed epileptic seizures, mainly manifested as generalized and absent seizures. She took the medicine of levetiracetam and lamotrigine, and the seizures were under control. Patient 2, a 6-months old boy, visited our department due to developmental regression and seizures. He showed poor reactions to light and sound, and was not able to raise head without aid. Hypotonia was also noticed. The electroencephalogram showed intermittent hyperarrhythmia, and spasms were monitored. He was given topiramate and adrenocorticotrophic hormone (ACTH). Whole exome sequencing detected a de novo c.592C>T (Q198X) mutation in NEXMIF gene. During the follow-up period, the seizures were reduced with vigabatrin. He had no obvious progress in the psychomotor development, and presented strabismus. There were 91 cases reported abroad, 1 case reported in China, and 2 patients were included in this study. A total of 85 variants in NEXMIF gene were found, involving 83 variants reported in PubMed and HGMD, and the 2 new variants presented in our patients. The patients with variants in NEXMIF gene all had mild to severe intellectual disability. Behavioral abnormalities, epilepsy, hypotonia, and other neurological symptoms are frequently presented. The phenotype of male partially overlaps with that of female. Male patients often have more severe intellectual disability, impaired language, and autistic features, while female patients often have refractory epilepsy. Most of the variants reported so far were loss-of-function resulted in the reduced protein expression of NEXMIF. The degree of NEXMIF loss appears to correlate with the severity of the phenotype.
Child ; Epilepsy/genetics* ; Female ; Humans ; Intellectual Disability/genetics* ; Male ; Muscle Hypotonia/complications* ; Mutation ; Phenotype ; Seizures/genetics* ; Strabismus/complications*

Objective:To evaluate the adjuvant role of the eCura scoring system in selecting appropriate treatment strategies after non-curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) patients.Methods:The clinicopathological data of 110 EGC patients who underwent non-curative ESD at Fujian Provincial Hospital from January 2015 to June 2019 were retrospectively analyzed. According to the eCura score, patients were divided into three lymph node metastasis (LNM) risk groups: low-risk group (79 cases), middle-risk group (22 cases), and high-risk group (9 cases). The receiver operator characteristic (ROC) curve analysis was used to test the diagnostic efficacy of eCura scoring system in predicting LNM. Logistic regression analysis was used to explore the influence of risk stratification of eCura scoring system on LNM. Kaplan-Meier method was used to evaluate cancer survival rate, which was then compared with log-rank test.Results:Thirty-five patients underwent additional standard surgery after ESD, including 22 in the low-risk group, 8 in the middle-risk group, and 5 in the high-risk group. Among them, 5 cases had LNM, including 1 case in the low-risk group and the middle-risk group respectively and 3 cases in the high-risk group. The area under the ROC curve was 0.857 (95% CI: 0.697-0.952, P=0.001), and when the cut-off value of the eCura score was set at 3, the Yuden index reached the maximum value of 0.7, with the corresponding sensitivity and specificity of 80% and 90%, respectively. Logistic regression analysis showed that the probability of LNM in the middle-risk group was about 3.00 times (95% CI: 0.17-54.57, P=0.458) as high as that in the low-risk group, and the probability of LNM in the high-risk group was about 31.50 times (95% CI: 2.14-463.14, P=0.012) of that in the low-risk group. The follow-up time was 12 to 58 months, and the median follow-up time was 40 months. There were 10 cases of recurrence, including 4 cases in the low-risk group, 3 cases in the middle-risk group and 3 cases in the high-risk group, of which 2 cases in the low-risk group were from those of additional standard surgery after ESD, and the remaining 8 cases were from those who did not receive additional standard surgery after ESD. Kaplan-Meier survival curve analysis showed that the survival rate of patients with additional surgery in the low-risk group was similar to that of patients without ( P=0.319), and the survival rate of patients with additional surgery in the middle-risk group was also similar to that of patients without ( P=0.296). The survival rate of patients with additional surgery in the high-risk group was significantly higher than that of those without ( P=0.013). Conclusion:The eCura scoring system can assist the selection of treatment strategies after non-curative resection of EGC, and can accurately predict the risk of subsequent LNM and recurrence. Close follow-up may be an acceptable option for patients with low risk of LNM, and additional standard surgical treatment may be more conducive to improving the prognosis in patients with high risk of LNM.

Objective:To evaluate type B2 vessels for predicting the invasion depth of superficial esophageal squamous cell carcinoma (SESCC) under narrow band imaging-magnifying endoscopy (NBI-ME), and to analyse the influencing factors of over-prediction and under-prediction.Methods:A total of 86 SESCC patients with 86 lesions confirmed by postoperative pathology, who underwent NBI-ME to evaluate the invasion depth of esophageal tumor and were observed for type B2 vessels in Department of Digestive Endoscopy of Fujian Provincial Hospital from January 2015 to April 2020, were included in the case-control study. According to the postoperative pathological results, the patients were divided into the correct prediction group ( n=25) and the wrong prediction group ( n=61), and the accuracy of prediction was calculated. The wrong prediction group was further divided into the over-prediction group ( n=49) and the under-prediction group ( n=12) to find the influencing factors of over-prediction and under-prediction, respectively. Further, multivariate Logistic analysis was performed to explore the independent influential factors for the prediction. Results:The accuracy of type B2 vessels under NBI-ME for predicting the invasion depth of SESCC was only 29.07% (25/86), and the over-prediction rate and under-prediction rates were 56.98% (49/86) and 13.95% (12/86), respectively. Univariate analysis showed that the classification of type B2 area ( χ2=36.25, P<0.001), the distinct endoscopic features (nodules, thickening and obvious depression, χ2=22.90, P<0.001), and inflammation around type B2 vessels ( χ2=9.54, P=0.004) were related to the over-prediction of the invasion depth of SESCC, and the distinct endoscopic features were related to the under-prediction of the invasion depth ( P=0.016). Multivariate Logistic regression analysis showed that B2-narrow (type B2 area ≤5 mm) ( P<0.001, OR=241.988,95% CI:15.229-3 845.252) and inflammation around type B2 vessels ( P=0.033, OR=12.801, 95% CI: 1.226-133.713) were independent risk factors for over-predicting the invasion depth of SESCC, while the distinct endoscopic features were independent protective factors for over-prediction ( P<0.001, OR=0.012, 95% CI: 0.001-0.150). The distinct endoscopic feature was an independent risk factor for under-predicting invasion depth of SESCC with type B2 vessels ( P=0.027, OR=7.899, 95% CI: 1.259-49.565). Conclusion:The accuracy of predicting the invasion depth of SESCC is low only based on type B2 vessels in NBI-ME, and over-prediction is prone to occur. B2-narrow, inflammation around type B2 vessels and without nodules, thickening and obvious depression are closely related to the over-prediction of invasion depth of SESCC by type B2 in NBI-ME, and nodules, thickening and obvious depression are closely associated with the under-prediction. However, whether the combined assessment of type B2 vessels under NBI-ME and endoscopic manifestation can improve the accuracy of prediction needs to be confirmed by further studies.

Natural extracellular vesicles (EVs) play important roles in many life processes such as in the intermolecular transfer of substances and genetic information exchanges. Investigating the origins and working mechanisms of natural EVs may provide an understanding of life activities, especially regarding the occurrence and development of diseases. Additionally, due to their vesicular structure, EVs (in small molecules, nucleic acids, proteins, etc.) could act as efficient drug-delivery carriers. Herein, we describe the sources and biological functions of various EVs, summarize the roles of EVs in disease diagnosis and treatment, and review the application of EVs as drug-delivery carriers. We also assess the challenges and perspectives of EVs in biomedical applications.

Objective:To explore the expression of circular RNA circ-MYBL2 in prostate cancer tissue and the molecular mechanism of its influence on the occurrence and metastasis of prostate cancer.Methods:From February 2017 to April 2021, 45 cases of prostate cancer tissues and paracancerous tissues from patients with prostate cancer in the Department of Urology, Jingmen No.2 People′s Hospital were selected. quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) was used to detect the difference in expression of circ-MYBL2 in prostate cancer tissues and adjacent tissues, and the difference in expression of circ-MYBL2 in prostate cancer cell lines and immortalized prostate duct epithelial cells. Cell lines with low circ-MYBL2 expression were respectively transfected with circ-MYBL2 plasmid (circ-MYBL2 group) or negative control plasmid (control group). qRT-PCR was used to detect the transfection efficiency of circ-MYBL2 plasmid. CCK-8 method and cell scratch test were used to detect the effect of circ-MYBL2 on cell proliferation and migration. The starBase v2.0 software was used to predict the miRNA bound by circ-MYBL2 and the target gene of miRNA. The dual luciferase reporter gene experiment was used to verify the regulatory relationship between circ-MYBL2 and miRNA. qRT-PCR was used to detect the influence of circ-MYBL2 on miRNA expression and the influence of miRNA on target gene mRNA expression. Western blotting was used to detect the expression of target gene protein and Wnt/β-catenin signaling pathway proteins. The measurement data were expressed as mean±standard deviation ( Mean± SD), the comparison between the means of multiple samples used one-way analysis of variance, and the comparison between the means of two samples used the t-test. Results:The expression of circ-MYBL2 of DU-145 cells in prostate cancer tissue was significantly lower than that in adjacent tissues ( P<0.01). The expression of circ-MYBL2 in prostate cancer cell lines was significantly lower than that of prostate ductal epithelial cells ( P<0.01), and the expression of DU-145 cells was the lowest ( P<0.01). Compared with the control group, the expression of circ-MYBL2 of DU-145 cells in the circ-MYBL2 group increased significantly ( P<0.01), and circ-MYBL2 reduced the proliferation activity ( P<0.05) and migration ability ( P<0.01) of DU-145 cells. circ-MYBL2 acted as a sponge to adsorb miR-324-3p, and miR-324-3p complementarily bound to the suppressor of SUFU gene. circ-MYBL2 inhibited the expression of miR-324-3p ( P<0.01), SUFU gene expression was increased ( P<0.01), and Wnt/β-catenin signal pathway transduction was inhibited. Conclusion:circ-MYBL2 promotes the expression of SUFU gene by adsorbing miR-324-3p, inhibits the Wnt/β-catenin signaling pathway, thereby reducing the proliferation activity and migration ability of prostate cancer cells.

Objective:To preliminarily study the effect of Q self-traction endoscopic submucosal dissection (Q-ESD) on treatment of large early esophageal cancer (EEC).Methods:A retrospective analysis was performed on the data of 82 cases of large EEC (single lesion>1/2 cross-section diameter or longitudinal diameter length >5 cm) who underwent ESD on Fujian Provincial Hospital between January 2015 and December 2018. According to the treatment schedule, patients were divided into the conventional ESD group (n=44) and the Q-ESD group (n=38). The procedural area, time, and speed, en bloc resection rate, complete resection rate and complications of the two groups were analyzed.Results:All of the 82 lesions were resected completely under endoscope. There was no statistical difference in the procedural area [779.8 (329.9-2 552.5)mm 2 VS 875.7 (417.8-1 914.8)mm 2, U=155, P=0.636], procedural time [63 (41-177)min VS 59 (42-169)min, U=171, P=0.167] and complete resection rate [94.7% (36/38) VS 93.2% (41/44), χ2=0.086, P=0.769] between the Q-ESD group and the conventional ESD group. Compared with the conventional ESD group, the Q-ESD group had a faster dissection speed [14.9 (5.4-20.8) mm 2/min VS 9.0 (5.0-19.5) mm 2/min, U=142, P=0.035], lower muscularis propria injury rate [7.9% (3/38) VS 27.3% (12/44), χ2=5.123, P=0.023], and a lower stricture rate [5.3% (2/38) VS 20.5% (9/44), χ2=4.051, P=0.044]. No other adverse events occurred except for one case of perforation in the conventional ESD group. Conclusion:The new traction technique of Q-ESD is a safe and effective treatment for large EEC.

Objective:To evaluate the efficacy and safety of budesonide viscous suspension (BVS) in preventing extensive esophageal stenosis after endoscopic submucosal dissection(ESD).Methods:Data of 62 cases of early esophageal neoplasms or precancerous lesions receiving ESD whose postoperative mucosal defects were more than half the circumference of the esophageal lumen at Fujian Provincial Hospital from October 2014 to December 2018 were retrospectively studied. The patients were divided into the BVS group who received BVS therapy (n=24) and the control group who received no intervention (n=38). The incidence of postoperative stenosis, the number of bougie dilation procedures and complications were compared between the two groups. Risk factors for postoperative stricture were analyzed by logistic regression.Results:The incidence of postoperative stenosis [16.7% (4/24) VS 47.3% (18/38), P=0.005], the number of bougie dilation procedures (1.50±0.58 VS 2.70±1.09, P=0.039) in the BVS group were significantly lower than those in the control group. No serious adverse events such as perforation or massive hemorrhage related to BVS were observed in the BVS group. Multivariate logistic regression analysis showed circumferential extension ≥3/4 ( OR=37.970, 95% CI: 6.338-227.482) and non-intervention with BVS( OR=20.962, 95% CI: 3.374-130.243) were the independent risk factors for esophageal stricture after ESD. Conclusion:Administration of BVS is an effective and safe method to reduce the incidence of stenosis and the number of bougie dilation procedures for extensive esophageal stenosis after ESD.

Objective:To evaluate the accuracy of white light conventional endoscopy (CE), endoscopic ultrasonography (EUS) and narrow-band imaging with magnifying endoscopy (ME-NBI) in evaluating the invasion depth of early gastric cardiac cancer, and to explore the diagnostic strategy of preoperative evaluation of invasive depth of early gastric cardiac cancer.Methods:From January 2016 to June 2019, the endoscopic images of 135 patients with early gastric cardiac cancer confirmed by pathology in Fujian Provincial Hospital were retrospectively analyzed. Intramucosal carcinoma (M) and superficial submucosal invasive carcinoma (SM1) were classified as M-SM1 cancer and compared with deep submucosal invasive cancer. The pathological diagnosis after operation was used as gold standard. The accuracy of CE, EUS, ME-NBI and the combination of them in determining the invasion depth of early gastric cardiac cancer was evaluated. Kappa test was performed for consistency test. Kappa value < 0.2 was considered as poor consistency, 0.2 to 0.4 as general consistency, more than 0.4 to 0.6 as medium consistency, more than 0.6 to 0.8 as high consistency, and 0.8 to 1.0 as close to full consistency. Results:The data of 73 patients with early gastric cardiac cancer were enrolled in this study. According to the pathological results after operation, 47 cases were M-SM1 cancer and 26 cases were deep submucosal invasive cancer. The diagnostic accuracy of CE, EUS, ME-NBI and the combination of them before operation were 79.5% (58/73), 72.6% (53/73), 65.7% (48/73) and 87.7% (64/73), respectively. The results of consistency test indicated that the consistency of CE diagnosis and pathological results after operation was medium ( Kappa=0.540, P<0.01), that of EUS and pathological results after operation was general ( Kappa=0.346, P=0.002), that of ME-NBI and pathological results after operation was poor ( Kappa=0.175, P=0.108), while that of the combination of them and pathological results after operation was high ( Kappa=0.724, P<0.01). Conclusions:Compared with single examination method, the combination of CE, EUS and ME-NBI is more accurate in evaluating the invasive depth of early gastric cardiac cancer.