Small extracellular vesicles facilitate epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps via the miR-375-3p/QKI axis.

BACKGROUND: Epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the involvement of small extracellular vesicles (sEVs) in EMT and their contributions to CRSwNP has not been extensively investigated. METHODS: SEVs were isolated from nasal mucosa through ultracentrifugation. MicroRNA sequencing and reverse-transcription quantitative polymerase chain reaction were employed to analyze the differential expression of microRNAs carried by sEVs. Human nasal epithelial cells (hNECs) were used to assess the EMT-inducing effect of sEVs/microRNAs. EMT-associated markers were detected by western blotting and immunofluorescence. Dual-luciferase reporter assay was performed to determine the target gene of miR-375-3p. MicroRNA mimic, lentiviral, and plasmid transduction were used for functional experiments. RESULTS: In line with the greater EMT status in eosinophilic CRSwNP (ENP), sEVs derived from ENP (ENP-sEVs) could induce EMT in hNECs. MiR-375-3p was elevated in ENP-sEVs compared to that in control and nonENP. MiR-375- 3p carried by ENP-sEVs facilitated EMT by directly targeting KH domain containing RNA binding (QKI) at seed sequences of 913-919, 1025-1033, and 2438-2444 in 3'-untranslated region. Inhibition of QKI by miR-375-3p overexpression promoted EMT, which could be reversed by restoration of QKI. Furthermore, the abundance of miR-375-3p in sEVs was closely correlated with the clinical symptom score and disease severity. CONCLUSIONS: MiR-375-3p-enriched sEVs facilitated EMT by suppressing QKI in hNECs. The association of miR-375-3p with disease severity underscores its potential as both a diagnostic marker and a therapeutic target for the innovative management of CRSwNP.

[Current status and reflection on molecular diagnosis of birth defects].

Birth defects are a major problem threatening the health of children in China. Genetic factors play a major role in birth defect etiology. Molecular diagnosis is the key means for screening, diagnosing, and preventing birth defects caused by genetic factors. How to carry out large-scale and cost-effective molecular diagnosis in clinical practice is a major challenge in the prevention and treatment of birth defects in China. This article reviews the current status of birth defects in China, the application of molecular diagnostic technology in birth defect prevention and control, and the challenges in promoting its use, to provide references for clinical practice in birth defect molecular diagnosis.

[Analysis of pollen sensitization characteristics of artemisia allergic rhinitis in three urban and rural areas of Inner Mongolia].

Objective: To investigate the distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three urban and rural areas of Inner Mongolia. Methods: From March to October 2019, in 3 central cities (Chifeng, Hohhot, Ordos) and rural areas of Inner Mongolia, an epidemiological investigation method combining multi-stage stratified random sampling and face-to-face questionnaire survey was adopted to screen suspected AR patients, and skin prick test (SPT) was applied for diagnosis. At the same time, pollen monitoring was carried out in 3 areas to analyze the distribution and clinical sensitization characteristics of artemisia pollen.SPSS26.0 statistical software was used to process all the data. Chi-square test was used to compare rates among different age, sex, region and nationality, Spearman test was used to describe correlation analysis, and pairwise comparison of positive rates among multiple samples was used Bonferroni method. Results: Among the 6 393 subjects, 1 093 cases were diagnosed with AR, and the prevalence of AR was 17.10% (1 093/6 393). Among them, pollen-induced allergic rhinitis, the prevalence of PiAR was 10.97% (701/6 393), accounting for 64.14%(701/1 093).The highest incidence was in the youth group (20-39 years old), accounting for 46.94% (329/701).The diagnosed prevalence was higher in females than in males (11.35% vs. 10.64%, χ2 value 12.304, P<0.001).The prevalence rate of ethnic minority was higher than that of Han nationality (13.01% vs. 10.65%, χ2 value 6.296, P=0.008).The prevalence in urban areas was also significantly higher than that in rural areas (18.40% vs. 5.50%, χ2 value 10.497, P<0.001).There was significant difference in prevalence rate among the three regions in Inner Mongolia (6.06% in Chifeng, 13.46% in Hohhot, 16.39% in Ordos, χ2 value 70.054, P<0.001).The main clinical symptoms of artemisia PiAR were sneezing (95.58%), nasal congestion (91.73%) and nasal itching (89.30%).Allergic conjunctivitis accounted for 79.60% (558/701), chronic sinusitis for 55.63% (390/701), asthma for 23.25% (163/701).The pattern of artemisia pollen sensitization was mainly multiple sensitization, and the frequency of clinical symptoms and clinical diseases induced by hypersensitization with other allergens accounted for more than that caused by single artemisia pollen. The spread period of Artemisia pollen in the three regions was from June to October, and the peak state was in August in summer. The peak time of clinical symptoms in artemisia PiAR patients was about 2 weeks earlier than the peak time of pollen concentration, and the two were significantly positively correlated (R=0.7671, P<0.001). Conclusion: Artemisia pollens are the dominant pollens in late summer and early autumn in Inner Mongolia, and the prevalence of artemisia PiAR is high. Controlling the spread of Artemisia pollens is of great significance for the prevention and treatment of AR.

[Comparative study of ultrasound and magnetic resonance imaging in the diagnosis of asymptomatic anterosuperior acetabular labrum tears].

OBJECTIVE: To explore the diagnostic value of ultrasound for asymptomatic anterosuperior acetabular labral tears (ALT). METHODS: From August 2018 to February 2020, a total of 64 asymptomatic volunteers (101 hips) were recruited to complete 3.0T magnetic resonance imaging (MRI) and ultrasound examination. Among these asymptomatic volunteers, 31 were male and 33 were female, with the median age 35 (32, 39) years. Using 3.0T MRI findings as golden standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ultrasound were calculated. RESULTS: The results showed the presence of unilateral or bilateral ALT in 33 (51.56%) asymptomatic vo-lunteers with a total of 47 hips (46.53%). Of the 37 asymptomatic volunteers with bilateral hip MRI examination, 14 had bilateral ALT and 8 had unilateral ALT. Of the 27 asymptomatic volunteers who underwent unilateral hip MRI, 11 had ALT. Of the 33 asymptomatic volunteers with labral tears, 11 were male and 22 were female, with 30 right hips and 17 left hips. The median age was 36 (33, 40) years in the ALT group and 34 (32, 38) years in the non-ALT group. There was no significant difference in age between the two groups (P > 0.05). In the asymptomatic population, the abnormal anterosuperior acetabular labrum manifestations on ultrasound were intra-labrum cleft in 26 cases, labral heterogeneous echogenicity in 25 cases, paralabral cysts in 2 cases, and labral focal hyperechoic area in 12 cases. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for ALT diagnosed by ultrasound were 73.53%, 67.16%, 53.19%, 83.33% and 69.31%, respectively. The cross- sectional area (CSA) of the anterosuperior acetabular labrum was 0.20 (0.15, 0.24) cm2 in this study. The labral median CSA of the ALT group and non-ALT group were 0.22 (0.17, 0.28) cm2 and 0.17 (0.14, 0.21) cm2, respectively, with a statistically significant difference (P < 0.001). CONCLUSION: The ALT are common findings in asymptomatic volunteers on MRI. Intra-labrum cleft and labral heterogeneous echogenicity are common ultrasonographic signs in asymptomatic volunteers with ALT. The labra were more swollen in the asymptomatic volunteers with ALT compared to those without ALT.

[Analysis of fast-growing culturable bacteria and pathogenic bacteria in the surface water of the northeast coast of Hainan Island in China].

Objective: To obtain the diversity and abundance of fast-growing bacteria in the surface water of the northeast coast of Hainan Island in China, different cultivation methods were employed. This study also aims to provide a reference for isolating bacterial samples from seawater sources and preventing marine-derived pathogens. Methods: Based on the principles of taxonomic design, surface seawater samples were collected from six locations along the northeast coast of Hainan Island in China in March, June, October, and December 2021. Then, bacterial enrichment was performed based on traditional cultivation methods for Salmonella, Vibrio, Burkholderia pseudomallei, Actinomycetes, and general marine bacteria. After that, bacterial species identification was conducted by 16S rDNA amplicon sequencing and metagenomic sequencing. Results: A total of 1 151 fast-growing cultivable bacteria belonging to 66 genera and 213 species were identified using five different culture protocols. In different cultivation protocols, Bacillus and Klebsiella demonstrated extensive discriminatory advantages and ranked among the top genera in terms of abundance. Protocol 1 had Escherichia, Klebsiella, and Citrobacter as dominant genera. Pathogenic bacteria detected by protocol 1 included Klebsiella pneumoniae and Escherichia coli, with 37 and 29 strains respectively, while Salmonella enterica was uniquely detected with seven isolates. Proteus, Enterococcus, and Providencia were the dominant genera in protocol 2, and Proteus mirabilis was the most abundant pathogenic bacteria detected with 66 isolates. Vibrio cholerae was uniquely detected with six isolates at a higher abundance. Klebsiella, Escherichia, and Acinetobacter were the dominant genera in protocol 3, and Klebsiella pneumoniae was the most abundant pathogenic bacteria detected with 53 isolates, while Acinetobacter nosocomialis was uniquely detected with seven isolates. Vibrio and Pseudoalteromonas were the dominant genera in protocol 4, and they showed advantages in isolating and cultivating Marine-derived Vibrio. Exiguobacterium, Staphylococcus, and Bacillus were the dominant genera in protocol 5. Bacillus cereus and Lactococcus lactis were the most abundant pathogenic bacteria detected with 20 and 15 isolates, respectively, while Lactococcus lactis was uniquely detected at higher abundance. Metagenomic sequencing showed that Klebsiella pneumoniae was significantly dominant with a gene abundance of 51.11%, followed by Alcanivorax sp. at 12.57%. Conclusion: The surface water of the northeast coast of Hainan Island in China exhibits a rich diversity of bacteria, with Klebsiella pneumoniae being highly abundant in the studied area. Different cultivation methods demonstrate distinct selective advantages in culturing bacterial genera and pathogens. Therefore, it is necessary to optimize cultivation conditions for specific marine bacteria.

[Endoscopic resection of type D trigeminal schwannoma through nasal sinus approach].

Objective: To examine the feasibility and surgical approach of removing type D trigeminal schwannoma through nasal cavity and nasal sinus under endoscope. Methods: Eleven patients with trigeminal schwannoma who were treated in the Department of Otorhinolaryngology, Qilu Hospital of Shandong University from December 2014 to August 2021 were analyzed retrospectively in this study. There were 7 males and 4 females, aged (47.5±13.5) years (range: 12 to 64 years). The neoplasm involved the pterygopalatine fossa, infratemporal fossa, ethmoidal sinus, sphenoid sinus, cavernous sinus, and middle cranial fossa. The size of tumors were between 1.6 cm×2.0 cm×2.0 cm and 5.7 cm×6.0 cm×6.0 cm. Under general anesthesia, the tumors were resected through the transpterygoid approach in 4 cases, through the prelacrimal recess approach in 4 cases, through the extended prelacrimal recess approach in 2 cases, and through the endoscopic medial maxillectomy approach in 1 case. The nasal endoscopy and imaging examination were conducted to detect whether neoplasm recurred or not, and the main clinical symptoms during follow-up. Results: All the surgical procedures were performed under endonasal endoscope, including Gross total resection in 10 patients. The tumor of a 12-year-old patient was not resected completely due to huge tumor size and limited operation space. One patient was accompanied by two other schwannomas located in the occipital region and the ipsilateral parotid gland region originating from the zygomatic branch of the facial nerve, both of which were removed concurrently. After tumor resection, the dura mater of middle cranial fossa was directly exposed in the nasal sinus in 2 cases, including 1 case accompanied by cerebrospinal fluid leakage which was reconstructed by a free mucosal flap obtained from the middle turbinate, the other case was packed by the autologous fat to protect the dura mater. The operation time was (M(IQR)) 180 (160) minutes (range: 120 to 485 minutes). No complications and deaths were observed. No recurrence was observed in the 10 patients with total tumor resection during a 58 (68) months' (range: 10 to 90 months) follow-up. No obvious change was observed in the facial appearance of all patients during the follow-up. Conclusion: Type D trigeminal schwannoma involving pterygopalatine fossa and infratemporal fossa can be removed safely through purely endoscopic endonasal approach by selecting the appropriate approach according to the size and involvement of the tumor.

[Study on risk factors of abnormal pulmonary function among dust-exposed workers and prediction model].

Objective: To explore the influencing factors of abnormal pulmonary function in dust-exposed workers and establish the risk prediction model of abnormal pulmonary function. Methods: In April 2021, a total of 4255 dust exposed workers from 47 enterprises in 2020 were included in the study. logistic regression was used to analyze the influencing factors of abnormal pulmonary function in dust-exposed workers, and the corresponding nomogram prediction model was established. The model was evaluated by ROC curve, Calibrationpolt and decision analysis curve. Results: logistic regression analysis showed that age (OR=1.03, 95%CI=1.02~1.05, P<0.001) , physical examination type (OR=4.52, 95%CI=1.69~12.10, P=0.003) , dust type (Comparison with coal dust, Cement dust, OR=3.45, 95%CI=1.45~8.18, P=0.005, Silica dust (OR=2.25, 95%CI=1.01~5.03, P=0.049) , blood pressure (OR=1.63, 95%CI=1.22~2.18, P=0.001) , creatinine (OR=0.08, 95%CI=0.05~0.12, P<0.001) , daily exposure time (OR=1.06, 95%CI=1.10~1.12, P=0.034) and total dust concentration (OR=1.29, 95%CI=1.08~1.54, P=0.005) were the influencing factors of abnormal pulmonary function. The area under the ROC curve of risk prediction nomogram model was 0.764. The results of decision analysis curve showed that the nomogram model had reference value in the prevention and intervention of abnormal pulmonary function when the threshold probability exceeded 0.05. Conclusion: The accuracy ofthe nomogram model constructed by logistic regression werewell in predicting the risk of abnormal lung function of dust-exposed workers.

[Analysis of clinicopathological features of 68 cases of malignant pleural mesothelioma].

Objective: To analyze the clinicopathological characteristics of diffuse malignant pleural mesothelioma (MPM), and explore the diagnostic methods in order to improve the early diagnosis rate. Methods: In January 2019 to January 2022, the clinical features, auxiliary examination and immunohistochemical results of 68 cases of MPM were analyzed retrospectively. The pathogenic features, histopathological morphology and the expression of related antibodies including Calretinin (CR), D2-40 and WT-1 were summarized. Results: Among the 68 patients, 40 male (58.82%), 28 female (41.18%), male to female ratio was 1.43%, median age was 58 years old; 50% of patients in Dayao County, epithelial mesothelioma 59 cases (86.76%), occurred in right chest in 39 cases (57.35%), left chest in 25 cases (36.76%), and 4 cases in both sides (5.89%). The most common initial clinical manifestations were pleural effusion (95.59%), chest pain (36.75%), chest tightness and shortness of breath (30.88%). The main imaging findings were pleural effusion in 49 cases (98.00%) and pleural thickening in 46 cases (92.00%). MPM tumor cells often expressed Calretinin, CK5/6, WT1 and D2-40, while TTF-1, NapsinA and CEA, the main markers differentiated from lung adenocarcinoma were negative. Serum CYFRA21-1 and CEA have high value in differential diagnosis of benign and malignant pleural effusions. Conclusion: Diffuse MPM has diverse histological and cytological morphology, which needs to be differentiated from a variety of diseases. Correct diagnosis of diffuse MPM through immunohistochemistry requires the combined application of a group of Mesothelium related antibodies.

Organ-specific metastatic landscape dissects PD-(L)1 blockade efficacy in advanced non-small cell lung cancer: applicability from clinical trials to real-world practice.

BACKGROUND: Organ-specific metastatic context has not been incorporated into the clinical practice of guiding programmed death-(ligand) 1 [PD-(L)1] blockade, due to a lack of understanding of its predictive versus prognostic value. We aim at delineating and then incorporating both the predictive and prognostic effects of the metastatic-organ landscape to dissect PD-(L)1 blockade efficacy in non-small cell lung cancer (NSCLC). METHODS: A total of 2062 NSCLC patients from a double-arm randomized trial (OAK), two immunotherapy trials (FIR, BIRCH), and a real-world cohort (NFyy) were included. The metastatic organs were stratified into two categories based on their treatment-dependent predictive significance versus treatment-independent prognosis. A metastasis-based scoring system (METscore) was developed and validated for guiding PD-(L)1 blockade in clinical trials and real-world practice. RESULTS: Patients harboring various organ-specific metastases presented significantly different responses to immunotherapy, and those with brain and adrenal gland metastases survived longer than others [overall survival (OS), p = 0.0105; progression-free survival (PFS), p = 0.0167]. In contrast, survival outcomes were similar in chemotherapy-treated patients regardless of metastatic sites (OS, p = 0.3742; PFS, p = 0.8242). Intriguingly, the immunotherapeutic predictive significance of the metastatic-organ landscape was specifically presented in PD-L1-positive populations (PD-L1 > 1%). Among them, a paradoxical coexistence of a favorable predictive effect coupled with an unfavorable prognostic effect was observed in metastases to adrenal glands, brain, and liver (category I organs), whereas metastases to bone, pleura, pleural effusion, and mediastinum yielded consistent unfavorable predictive and prognostic effects (category II organs). METscore was capable of integrating both predictive and prognostic effects of the entire landscape and dissected OS outcome of NSCLC patients received PD-(L)1 blockade (p < 0.0001) but not chemotherapy (p = 0.0805) in the OAK training cohort. Meanwhile, general performance of METscore was first validated in FIR (p = 0.0350) and BIRCH (p < 0.0001), and then in the real-world NFyy cohort (p = 0.0181). Notably, METscore was also applicable to patients received PD-(L)1 blockade as first-line treatment both in the clinical trials (OS, p = 0.0087; PFS, p = 0.0290) and in the real-world practice (OS, p = 0.0182; PFS, p = 0.0045). CONCLUSIONS: Organ-specific metastatic landscape served as a potential predictor of immunotherapy, and METscore might enable noninvasive forecast of PD-(L)1 blockade efficacy using baseline radiologic assessments in advanced NSCLC.

Effect of Al substitution on the magnetization reversal and complex magnetic properties of NiCr2O4 ceramics.

A series of polycrystalline NiCr2-xAlxO4 (0.1 ≤ x ≤ 0.25) spinel ceramics have been synthesized using a sol-gel method. DC magnetization measurements are carried out at different temperatures and magnetic fields. A novel magnetization reversal has been observed in the field cooling process for the x = 0.2 sample, which can be ascribed to the competition between two magnetic sublattices due to their different temperature dependences. The magnetic interaction evolution, related to the complex magnetic properties, is revealed by exchange constants that have been estimated according to ferrimagnetic Curie-Weiss fitting and mean field theory. The fitting result confirmed the evolution of antiferromagnetic and ferromagnetic components with Al substitution, which is supported by the observations from the isothermal magnetization measurements. The positive and negative values of the magnetic moment can be utilized for storage applications based on the results of magnetic switching effect measurements.

[Comparison of clinical features between sporadic pancreatic neuroendocrine tumors and those associated with multiple endocrine neoplasia type 1].

Objective: To compare the clinical features of multiple endocrine adenoma type 1 (MEN-1) associated pancreatic neuroendocrine neoplasms (pNENs) as well as sporadic pNENs. Methods: The clinical data of 28 sporadic pNENs patients and 10 MEN-1-related pNENs patients admitted to the First Affiliated Hospital of Nanjing Medical University from January 2010 to June 2021 were collected. Meanwhile, by searching PubMed database and reviewing the clinical data of 20 foreign patients with MEN-1-related pNENs which were reported at the same time.Compare and analyze the similarities and differences between MEN1-associated pNENs and sporadic pNENs in clinical features, such as family history, blood tests, pathological diagnostic indicators, tumor grade, stage and metastasis, treatment and prognosis and so on. Results: A total of 58 pNENs patients were included, and there were 30 MEN1-related pNENs patients and 28 sporadic pNENs patients. Eighteen patients (60%) had a family history of MEN1-related pNENs, and the mean age of onset was (35.3±13.0)years. There were no patients (0) with family history of sporadic pNENs, and the mean age of onset was(55.3±13.4)years. In contrast, the differences in family history, age of onset and NSE were statistically significant(all P<0.05).Among the pathological diagnostic indicators, there were 19 patients (63.3%) with Grade G2 of MEN1-related pNENs, and 25 patients (83.3%) with somatostatin receptor 2(SSTR2) negative. In sporadic pNENs, there were 16 patients (57.1%) with Grade G2 and 9 patients (32.1%) with SSTR2 negative. The differences in pathological grade, immunohistochemistry (Chromogranin A, CD56, and somatostatin receptor 2, SSTR2) between the two groups were statistically significant(all P<0.05). In terms of tumor staging and metastasis, 21 patients with MEN-1-related pNENs had metastasis (70%) and 20 patients with stage Ⅰ and Ⅱ AJCC (71%) in all. Eight patients with sporadic pNENs had metastasis (26.7%) and 8 patients were with stage Ⅰ and Ⅱ AJCC (28.6%). By contrast, the differences in total metastasis rate, AJCC stage and distant metastasis between the two groups were statistically significant(all P<0.05). In terms of treatment and prognosis, there was no statistical significance in the differences between surgical treatment and prognosis (P>0.05), and the difference was also not statistically significant in survival rate between them (P>0.05). Conclusions: There are no significant differences between MEN1-related pNENs and sporadic pNENs in terms of treatment, prognosis, and survival rate, but there are significant differences in clinical features, pathological features and the staging and grading of tumors. The rate of tumor grade, stage and metastasis of sporadic pNENs is higher.

[Value of indocyanine green fluorescence tracer in laparoscopic cholecystectomy for acute cholecystitis].

Objective: To explore the value of low-dose indocyanine green (ICG) fluorescence imaging in laparoscopic cholecystectomy (LC) for acute cholecystitis. Methods: Clinical data of 198 patients with acute cholecystitis and had received LC in Changzhou No.2 People's Hospital from January 2020 to September 2021 were collected. In the fluorescence group (n=97), peripheral intravenous injection of ICG was performed 15 minutes before LC, while conventional white light was applied in the control group (n=101). The efficiency of bile duct discrimination, operation time, intraoperative bleeding and postoperative complications were compared between the two groups. Results: Of the 198 patients, 86 were males and 112 females. The differences were not statisticly significant in age [52 (44, 63) vs 56 (46, 68) years, P>0.05], history of chronic inflammation [34(35.1%) vs 31(30.7%) cases, P>0.05] and other clinical baseline data between the two groups. Compared with the control group, the fluorescence group had higher efficiency of bile duct identification [18 (16,19) vs 38 (28,55) min,P<0.001], shorter operation time [45 (40,60) vs 80 (65,100) min,P<0.001], less intraoperative bleeding [10 (5,15) vs 60 (20,100) ml,P<0.001], and less postoperative liver function damage [alanine aminotransferase 35.0 (23.4,51.0) vs 98.3 (67.0,134.8)U/L,P<0.001]. In the control group, there was one case of biliary duct injury during operation, one case of postoperative biliary fistula, and one case of postoperative hemorrhage. No similar adverse event was found in fluorescence group. Conclusions: ICG fluorescence imaging can improve the efficiency of LC for patients with acute cholecystitis. It is easy to operate and has a good clinical application value.

[Altered dynamics of brain spontaneous activity in betel quid dependence chewers].

Objective: To investigate the dynamic characteristics of brain spontaneous activity in betel quid dependence (BQD) chewers and its relationship with clinical indexes. Method: This study was conducted in Hainan General Hospital from April to December 2019 and the data of 53 BQD chewers (37 males and 16 females, aged 20 to 58(38±11) years) and 37 healthy controls (HC) (24 males and 13 females, aged 23-57(42±12) years) were collected. All these subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scan. The dynamic characteristics of resting fMRI indexes, including dynamic amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and degree centrality (DC) of these subjects were calculated using the sliding time window method, parameters such as age and dynamic local consistency were analyzed and compared between the two groups. Pearson correlation was used to analyze the relationship between dynamic indexes, betel quid dependence score (BQDS) and disease duration in BQD group. Results: BQD chewers showed decreased dynamic ALFF in the left orbital prefrontal cortex (0.138±0.041 vs 0.171±0.070), the right temporal pole superior temporal gyrus (0.277±0.070 vs 0.319±0.086) and the right inferior parietal lobule (0.223±0.052 vs 0.259±0.088) than HC (all P<0.05). For regional homogeneity, BQD chewers showed a decrease dynamic ReHo in the right inferior temporal gyrus (0.055±0.008 vs 0.061±0.009), the orbital prefrontal cortex (0.058±0.005 vs 0.063±0.008), the right inferior frontal gyrus (0.081±0.006 vs 0.087±0.011), the right superior occipital gyrus (0.056±0.007 vs 0.062±0.008), the left precentral gyrus (0.068±0.008 vs 0.074±0.008), and the left superior frontal gyrus (0.058±0.008 vs 0.064±0.009) than HC (all P<0.05). BQD chewers showed an increase dynamic ReHo in the right precuneus (0.095±0.009 vs 0.089±0.008) (P<0.05). There was no significant difference in DC between the two groups (all P>0.05). The relationships between three dynamic ALFF and BQDS (r=-0.104, -0.015, -0.119), seven dynamic ReHo and BQDS (r=-0.099, -0.141, -0.055, -0.078, -0.027, -0.111, -0.090), three dynamic ALFF and disease duration (r=-0.122, -0.095, -0.171), and seven dynamic ReHo and disease duration (r=0.242, -0.252, 0.035, 0.056, 0.047, 0.081, 0.169) were not statistically significant (all P>0.05). Conclusions: BQD chewers showed a decrease dynamic ReHo and/or ALFF in multiple brain regions dominated by prefrontal cortex, and an increase dynamic ReHo in the right precuneus.

[Advance in pathogenesis of oligodendrocytes-associated autism spectrum disorder].

Autism spectrum disorder (ASD) is a serious neurodevelopmental impairment of children. Because of its difficulty of early diagnosis, length of disease course, irreversible injury and slim chance of curability, it brings heavy burdens to patients, their families and the whole society. Recent studies have shown that the pathogenic mechanism of ASD is closely related to the abnormal myelination caused by the imbalance of differentiation, proliferation and apoptosis of oligodendroglial lineage cells. This article will review on the role of oligodendroglial lineage cells in myelination and the mechanisms of ASD caused by improper differentiation, proliferation and apoptosis of oligodendroglial lineage cells, according to advanced researches. Oligodendrocytes play vital roles in neurodevelopment, and the defect in these cells has been recognized as one of the key pathogenic mechanisms leading to ASD. Elucidating the effects and disciplines which oligodendrocytes exert on the occurrence and development of ASD would provide guidance for precise prevention and control of neurodevelopmental disorders such as ASD.

[Advances of nanomaterials applied in ophthalmic treatment].

Nanomaterials have been used in many aspects of ophthalmic treatment. By emphasizing the ubiquitous characteristics of nanoparticles and composites, we first explained their relatively mature applications in drug delivery. Then we reviewed the research on nanomaterials in regenerative medicine and gene therapy in recent years. We also discussed the main limitations of the wider application of nanomaterials in ophthalmology: stability, biotoxicity and preclinical-clinical differences. The development of efficient and non-toxic nanomaterials, combined with appropriate transportation systems and application occasions, will provide more possibilities for the future application of nanomaterials in ophthalmic treatments.

Effects of lipids and surfactants on the fermentation production of echinocandin B by Aspergillus nidulans.

AIMS: Echinocandin B (ECB) is a kind of lipopeptide antifungal antibiotic, as well as the key precursor of antifungal drug Anidulafungin. Its efficient bioproduction plays an important role in promoting the industrial production of Anidulafungin. METHODS AND RESULTS: In this study, methyl oleate and Tween 80 were firstly used to enhance the ECB fermentation by Aspergillus nidulans, the results showed that the ECB titre was significantly enhanced with the addition of methyl oleate and Tween 80. Among the lipids, methyl oleate was found to play a pivotal role in increasing the ECB titre to 2123 mg l-1 , which was more than five times higher than that of the control. The addition of Tween 80 in the medium resulted in ECB titre increased to 2584 mg l-1 . The scanning electron microscope (SEM) and N-phenyl-1-naphthylamine (NPN) assay indicated that Tween 80 could influence the cell membrane permeability of A. nidulans, and enhance the intracellular and extracellular substance exchange, therefore lead to the increasing of ECB titre. CONCLUSIONS: Methyl oleate and Tween 80 are optimal carbon sources and surfactants for efficient ECB biosynthesis respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: Surfactant was used in ECB fermentation for the first time, which provided feasible ideas for optimizing the fermentation process of other fungi.

[Prognostic significance of DEK-NUP214 fusion gene in patients with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the dynamic change and clinical impact of DEK-NUP214 fusion gene in patients with acute myeloid leukemia (AML) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Real-time quantitative polymerase chain reaction (RQ-PCR) and multicolor flow cytometry (FCM) were used to detect DEK-NUP214 gene expression and leukemia-associated immunophenotype (LAIP) in 15 newly diagnosed patients with positive DEK-NUP214 and receiving allo-HSCT from September 2012 to September 2017 at Peking University People's Hospital. The clinical outcome was analyzed using Kaplan-Meier survival curves. The impact of DEK-NUP214 expression was analyzed by log-rank test. Results: The subjects were followed-up with a median period of 657 (62-2 212) days. The median DEK-NUP214 expression level at diagnosis was 488% (274%-1 692%). Thirteen patients achieved complete remission before allo-HSCT. Thirteen patients had a residual DEK-NUP214 expression of 0.38% (0.029%-738.9%) before allo-HSCT. After allo-HSCT, DEK-NUP214 expression in 9/13 patients remained positive, which dropped by around 500 folds (5.7-5 663.0 folds) within a month post-transplant. Five patients died and 2 patients relapsed. The 3-year cumulative incidence of relapse in patients with positive DEK-NUP214 before transplant was 17.5%±11.3% and the 3-year overall survival was 60.5%±13.8%. After allo-HSCT, DEK-NUP214-negative patients had a better outcome. Conclusion: Quantitative monitor of DEK-NUP214 fusion gene could be a sensitive indicator of MRD status after allo-HSCT.

[The effect of donor cytomegalovirus serological status on the outcome of allogeneic stem cell transplantation].

Objective: Donor cytomegalovirus (CMV) serological negative status may have an adverse effect on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT), while there is inadequate data for Chinese people. This study is to explore the impact of donor CMV serological status on the outcome of CMV seropositive patients receiving allo-HSCT. Methods: Our study retrospectively analyzed 16 CMV seropositive patients with hematological malignancies receiving allogeneic grafts from CMV seronegative donors (antibody IgG negative) at Peking University People's Hospital from March 2013 to March 2020, which was defined as D-/R+ group. The other 64 CMV seropositive patients receiving grafts from CMV seropositive donors at the same period of time were selected as matched controls through a propensity score with 1∶4 depending on age, disease state and donor-recipient relationship (D+/R+ group). Results: Patients in D-/R+ group developed CMV DNAemia later than patients in the D+/R+ group (+37 days vs. +31 days after allo-HSCT, P=0.011), but the duration of CMV DNAemia in D-/R+ group was longer than that of D+/R+ group (99 days vs. 34 days, P=0.012). The rate of CMV reactivation 4 times or more in D-/R+ group was 4/16, significantly higher than that of D+/R+ group (4.7%, 3/64, P=0.01). The incidences of refractory CMV DNAemia (14/16 vs. 56.3%, P=0.021) and CMV disease (4/16 vs. 4.7%, P=0.01) in D-/R+ group were both higher than those in D+/R+ group. In addition, the application of CMV-CTL as the second-line antiviral treatment in D-/R+ group was more than that in D+/R+ group. Univariate analysis and multivariate analysis suggested that CMV serological negativity is an independent risk factor for refractory CMV DNAemia and the duration of CMV infection. The cumulative incidence of aGVHDⅡ-Ⅳ, cGVHD, 3-year probability of NRM, overall survival, and the cumulative incidence of relapse were all comparable in two groups. Conclusions: Although there is no significant effect on OS and NRM, the incidence of refractory CMV DNAemia, the frequency of virus reactivation, and the development of CMV disease in D-/R+ group are higher than those in controls. Therefore, CMV seropositive donors are preferred for CMV seropositive patients.

[Prevention and control of birth defects and rare diseases in the era of genomic medicine].

Birth defects and rare diseases have become major public health problems, and early prevention and control are the most effective interventions. In recent years, with the rapid development of genomic techniques such as high-throughput sequencing, the level of screening and diagnosis of genetic birth defects and rare diseases has been greatly improved. This article reviews the application of genomic technologies in the pre-pregnancy, preimplantation, prenatal and neonatal stages, as well as the trend of clinical transformation, highlighting the broad prospects of constructing an early and precise prevention and control system in the era of genomic medicine.

Education intervention for older adults with osteoporosis: a systematic review.

BACKGROUND: Various education interventions were developed for preventing or managing OP, but the effects of those interventions on older adults were inconclusive. PURPOSE: This study evaluated the effectiveness of educational interventions in preventing osteoporosis in older adults. A literature search was performed in MEDLINE (PubMed), Cochrane Library, and CBM (China BioMed Database) from the initial date of each database to Oct 2016. DATA EXTRACTION: Two investigators independently extracted essential data from qualified studies concerning the settings, population, interventions, follow-ups, and outcomes of interest, namely effects of bone mineral density tests, changes in behavior, knowledge increase, self-efficacy, medication adherence (calcium and vitamin D), and quality of life, respectively. DATA SYNTHESIS: A total of 17 studies met the inclusion criteria and therefore were included in the current study. The overall quality of the included studies was moderate. We were unable to carry out a meta-analysis due to the heterogeneity of these studies. We fond that compared with control groups, patients' knowledge of osteoporosis increased significantly (p < .05) through all five interventions, which included PowerPoint presentations and discussion, class-based educational programs, osteoporosis self-management courses, revised health belief model and classes, computerized support programs and brush-up courses. LIMITATION: Studies included in the present study were all conducted in Western countries and only descriptive methods were applied in synthesis due to heterogeneity in interventions and outcomes. CONCLUSION: Education interventions were effective in preventing osteoporosis in older adults. Future research should focus on approaching this issue quantitatively (i.e., through meta-analysis).