[Relationship of diffusion kurtosis imaging parameters with the pathologic type and prognosis of rectal tumors].

Objective: To explore the application value of diffusion kurtosis imaging (DKI) in the differential diagnosis of rectal tumors and evaluating the prognostic factors associated with rectal adenocarcinoma. Methods: A total of 105 patients with rectal tumors admitted in the First Affiliated Hospital of Zhengzhou University from December 2018 to August 2020 were retrospectively analyzed. All patients underwent high-resolution magnetic resonance DKI scanning. The mean diffusivity (MD), mean kurtosis (MK) and apparent diffusion coefficient (ADC) were measured and the relationship of these parameters with pathological types and prognostic factors of rectal tumor were analyzed. The diagnostic efficacy of MD, MK, and ADC for positive circumferential resection margin (CRM) and extramural venous invasion (EMVI) of rectal adenocarcinoma was evaluated by the receiver operating characteristic (ROC) curve. Results: MD and ADC were only related to pathological type. The MD and ADC were (2.091±0.390)×10(-3) and (1.478±0.265)×10(-3) mm(2)/s in mucinous adenocarcinoma, higher than (1.136±0.182)×10(-3) and (0.767±0.077)×10(-3) mm(2)/s in unspecified adenocarcinoma and (1.617±0.697)×10(-3) and (0.940±0.179)×10(-3) mm(2)/s in tubulo-villous adenoma. The MD and ADC in unspecified adenocarcinoma were lower than those in tubule-villous adenoma (P<0.05). Nevertheless, MK was associated with pathological type, N stage, CRM and EMVI. The MK was 0.566±0.110 in mucinous adenocarcinoma, lower than 0.982±0.135 in unspecified adenocarcinoma and 0.827±0.121 in tubulo-villous adenoma. The MK in unspecified adenocarcinoma was higher than that in intubulo-villous adenoma. The MK was 0.984±0.107 in pN1-2, higher than 0.881±0.146 in pN0. The MK was 0.990±0.142 in positive CRM, higher than 0.862±0.114 in negative CRM. The MK was 0.996±0.140 in positive EMVI, higher than 0.832±0.100 in negative EMVI (P<0.05). The ROC curves showed that the AUCs of MD, MK and ADC in diagnosing positive CRM were 0.459, 0.653 and 0.408, respectively; with MK=1.006 as the optimal diagnostic threshold, the diagnostic sensitivity and specificity were 51.9% and 81.0%, respectively. The AUCs of MD, MK and ADC values in diagnosing positive EMVI were 0.510, 0.662 and 0.388, respectively; with MK=1.010 as the optimal diagnostic threshold, the diagnostic sensitivity and specificity were 50.9% and 87.5%, respectively. Conclusions: DKI quantitative parameter is helpful for discriminating rectal tubulo-villous adenoma, unspecified adenocarcinoma, and mucinous adenocarcinoma, and is helpful for predicting the prognosis of patients with rectal adenocarcinoma. High MK is associated with positive CRM and EMVI.

[Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors].

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

[Assessment of MS-Score and HScore in timeliness of diagnosis of macrophage activation syndrome associated with adult-onset Still's disease].

The data of 33 patients with adult-onset still's disease (AOSD)-associated macrophage activation syndrome (MAS) were retrospectively collected from January 2013 to December 2020 in Peking Union Medical College Hospital. Hemophagocytic lymphohistiocytosis (HLH)-2004 criteria, macrophage activation syndrome/juvenile idiopathic arthritis (MS-Score) and hemophagocytic syndrome diagnostic score (HScore) were used to diagnose AOSD-associated MAS, respectively. The time of diagnosis of AOSD-associated MAS by MS-Score was 19.0 (4.5, 31.0) days [M (Q1,Q3)] earlier than by HLH-2004 criteria, and 13.5 (0.5, 21.5) days earlier than by HScore (both P<0.05). The difference was not statistically significant between the time of diagnosis of AOSD-associated MAS by Hscore and by HLH-2004 criteria (P>0.05). There was significant difference among the three criteria (P<0.001). MS-Score can be used to diagnose AOSD-associated MAS earlier than HLH-2004 criteria, while the timeliness of HScore is not certain.

[A multicenter, randomized, double-masked, placebo-controlled trial of compound wild chrysanthemum eye masks for mild and moderate dry eye].

Objective: To investigate the clinical efficacy and safety of compound wild chrysanthemum eye masks for mild and moderate dry eye. Methods: In this double-masked, multicenter, placebo-controlled, randomized trial, middle-aged and elderly patients with mild and moderate dry eye were enrolled from six hospitals (Xiamen Eye Center of Xiamen University, China-Japan Friendship Hospital, Peking Union Medical College Hospital, Wangjing Hospital of China Academy of Chinese Medical Sciences, Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine and Hebei Eye Hospital). The patients were assigned to the compound wild chrysanthemum eye mask group and the eye mask simulator group based on the random number table. Subjective symptoms of dry eye, visual acuity, break-up time (BUT), Schirmer Ⅰ test, and corneal fluorescent staining were evaluated in all patients before treatment and at 1 and 2 weeks after treatment. All adverse reactions during the treatment and follow-up were recorded. Results: A total of 120 patients were enrolled. Among them, 112 subjects were included for statistical analyses after the exclusion of 8 subjects who were lost for follow-up or had an adverse event, with an age of (54.26±7.44) years. All the indicators were equally comparable between the two groups. Before treatment and at 1 and 2 weeks after treatment, the median (lower quartile, upper quartile) of total score of questionnaires in the eye mask group was 14.50 (10.00, 19.00), 9.00 (5.00, 14.00) and 7.00 (4.00, 10.00), respectively, and that in the control group was 14.00 (9.00, 22.50), 12.00 (6.00, 20.00) and 10.00 (3.50, 17.00), respectively. The score decreased significantly in both groups after 1 week (t=9.1604, S=398.00; P<0.01) and 2 weeks (S=681.00, 575.50; P<0.05) of treatment. The total score of questionnaires in the eye mask group was significantly lower than that in the control group (Z=3.27, 2.81; P<0.05) after treatment. After 1 week of treatment, the average BUT of the eye mask group was (5.71±2.31) s, which was significantly longer than that before treatment (5.06±2.00) s (S =208.50, P<0.05). But there was no significant difference in the control group (S=150.00, P>0.05). After 2 weeks of treatment, there was statistically significant difference in BUT between the two groups (S=407.00, t=3.07; P<0.01). After 1 week of the treatment, the amount of tear secretion in the eye mask group [(6.88±4.78) mm] was significantly larger than that before treatment (S=196.50, P<0.05), while the control group [(6.80±5.85) mm] showed no significant difference (S=55.00, P<0.05). After 2 weeks of the treatment, the amount increased significantly to (7.43±4.86) mm and (7.29±4.56) mm, respectively, in both groups (t=-3.29, -2.26; P<0.05). The difference in the average BUT, Schirmer Ⅰ test result and corneal fluorescent staining between both groups was not statistically significant at each time point. Five mild adverse events occurred, including 2 adverse events (2 times, 3.51%) in the eye mask group and 3 adverse events (4 times, 5.36%) in the control group. Conclusions: Compound wild chrysanthemum eye masks can effectively improve the symptoms and physical signs of mild and moderate dry eye and can be used as an auxiliary treatment. (Chin J Ophthalmol, 2021, 57: 601-607).

[Mediated pathways of exosomes uptake by stem cells of apical papilla].

OBJECTIVE: To evaluate the uptake of exosomes by stem cells from apical papilla (SCAP), thus to provide experimental basis for mechanism of the exosomes endocytosis by SCAP. METHODS: (1) Exosomes of dental pulp stem cells (DPSCs) were isolated by hypercentrifugation combined with ultrafiltration method. The exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis and western blot. (2) PKH-26 membrane labeling technology was used to mark the DPSCs derived exosomes. The labeled exosomes were co-cultured with SCAP at 37 °C as positive control group, and co-cultured with SCAP at 4 °C as the low-temperature treatment group, while the negative control group was set up. (3) Using clathrin-mediated endocytosis inhibitor chlorpromazine (CPZ, 10 µmol /L) as CPZ group, caveolae-mediated endocytosis Genistein (200 µmol/L) as Genistein group, and macropinocytosis inhibitor LY294002 (50 µmol/L) as LY294002 group to treat the SCAP respectively. Solvent control group (DMSO group) was set. Immunofluorescence staining was used to detect the red fluorescence SCAP and flow cytometry was used to analyze the proportion of SCAP labeled with red fluorescence. RESULTS: (1) The bilayer membrane and cup-shaped appearance of representative exosomes were observed. The peak of the size of DPSCs-derived exosomes was at 144 nm. The exosomes expressed exosomal marker proteins TSG101 and CD63, but not GAPDH which was the cellular internal control protein. (2) Immunofluorescence staining showed that after being co-cultured at 37 °C for 6 hours, red fluorescence could be detected in SCAP but it could not be detected after being co-cultured at 4 °C for 6 hours. After endocytosis inhibition, the red fluorescence in SCAP was reduced. Flow cytometry showed that the proportion of SCAP labeled with red fluorescence in positive group was 35.0%, in negative control group was 0.5%, and in solvent control group was 29.7%, in CPZ group, Genistein group and Genistein group were reduced to 13.7%, 16.6%, and 20.9%, respectively. CONCLUSION: SCAP could uptake the DPSCs derived exosomes, and low temperature could inhibit this process. The exosomes uptake of SCAP was mediated by the clathrin endocytosis pathway, caveolae-mediated endocytosis and macropinocytosis pathway.

[Analysis of the first cluster of cases in a family of COVID-19 in Gansu Province].

The epidemiological history and clinical characteristics of 7 cases of COVID-19 and 1 case of close contact in the first family aggregation epidemic of COVID-19 in Gansu Province were analyzed. The first patient A developed on January 22, 2020, with a history of residence in Wuhan, and confirmed severe cases of NCP on January 24, 2020; patient B, on January 23, 2020, diagnosed on January 31, severe cases; patient C, asymptomatic, diagnosed on January 27; patient D, asymptomatic, diagnosed on January 27; patient E, on January 24, diagnosed on January 28; patient F, asymptomatic, diagnosed on January 31; Patient G was asymptomatic and was diagnosed on January 31. In close contact, H was asymptomatic, PCR test was negative and asymptomatic, and he was discharged early. Among the 7 patients, 1 case died of (B) aggravation, and the other patients' condition was effectively controlled after active treatment. Except for the discharged cases, 5 cases were positive for COVID-19 specific IgM antibody and 1 case was negative. In this clustering outbreak, 4 patients remained asymptomatic, but PCR and IgM antibodies were positive, indicating that asymptomatic patients may be the key point to control the epidemic. Specific IgM antibody screening for patients whose pharyngeal swab nucleic acid test is negative but with ground glass-like lung lesions is very important for early detection and early isolation.

[Analysis of the first cluster of cases in a family of novel coronavirus pneumonia in Gansu Province].

The epidemiological history and clinical characteristics of 7 cases of COVID-19 and 1 case of close contact in the first family aggregation epidemic of COVID-19 in Gansu Province were analyzed. The first patient A developed on January 22, 2020, with a history of residence in Wuhan, and confirmed severe cases of NCP on January 24, 2020; patient B, on January 23, 2020, diagnosed on January 31, severe cases; patient C, asymptomatic, diagnosed on January 27; patient D, asymptomatic, diagnosed on January 27; patient E, on January 24, diagnosed on January 28; patient F, asymptomatic, diagnosed on January 31; Patient G was asymptomatic and was diagnosed on January 31. In close contact, H was asymptomatic, PCR test was negative and asymptomatic, and he was discharged early. Among the 7 patients, 1 case died of (B) aggravation, and the other patients' condition was effectively controlled after active treatment. Except for the discharged cases, 5 cases were positive for COVID-19 specific IgM antibody and 1 case was negative. In this clustering outbreak, 4 patients remained asymptomatic, but PCR and IgM antibodies were positive, indicating that asymptomatic patients may be the key point to control the epidemic. Specific IgM antibody screening for patients whose pharyngeal swab nucleic acid test is negative but with ground glass-like lung lesions is very important for early detection and early isolation.

[Role of endocytosis in cell surface CXC chemokine receptor 4 expression of stem cells from apical papilla].

OBJECTIVE: To evaluate the change of cell surface CXC chemokine receptor 4 (CXCR4) expression of stem cells from apical papilla (SCAP) after the inhibition of endocytotic pathway, thus to provide experimental basis for the mechanism of SCAP migration. METHODS: The immunofluorescence analysis was conducted to examine the co-expression of CXCR4 and endocytotic compartments, including early endosomes, recycling endosomes and lysosomes in SCAP. Several Rab proteins were applied as markers of organelles in the endocytotic pathway, including Rab5 for early endosomes, Rab11A for recycling endosomes, and Lamp1 for lysosomes. The co-localization of CXCR4 with these endodontic compartments was further observed by proximity ligation assay (PLA). SCAP was treated with two kinds of endocytotic inhibitors, Blebbistatin and Dynasore, at a concentration of 80 µmol/L, respectively. The conditioning time was 1 hour. Flow cytometry was carried out to evaluate the proportion of SCAP that expressed CXCR4 on cell surface. The data were analysed by analysis of variance (ANOVA). RESULTS: The red staining of CXCR4 on immunofluorescence confocal microscopy predominantly overlapped with the green staining of Rab5 and Rab11A, and partly overlapped with Lamp1. It indicated that most CXCR4 molecules were located in early endosomes and recycling endosomes, and some were located in lysosomes. The PLA results revealed that the co-localizaiton of CXCR4 with endocytotic compartments could be observed in early endosomes, recycling endosomes and lysosomes. According to the results of flow cytometry, the proportion of SCAP that expressed CXCR4 on cell surface was as low as 0.13%±0.10%. After the inhibition of endocytosis by pretreating the cells with the following two inhibitors, Blebbistatin and Dynasore, the percentage of SCAP that positively expressed CXCR4 on cell surface was significantly increased to 13.34%±1.31% in Blebbistatin group and 4.03%±0.92% in Dynasore group (F=16.721, P<0.001). Moreover, the number of SCAP that expressed CXCR4 on cell surface in Blebbistatin group was significantly higher than that in Dynasore group (P<0.001). CONCLUSION: The inhibition of endocytotic pathway could increase the number of SCAP that expressed CXCR4 on cell surface, and provide potency for the migration of SCAP.

[Relationship between overnight urinary sodium to potassium ratio and the risk of cardiovascular disease].

Objective: To explore the relationship between overnight urinary sodium to potassium ratio and the risk of cardiovascular disease (CVD). Methods: A subsample of 10 percent of the participants (35-59 years old) from the People's Republic of China-United States Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology (prospective survey) were used. Three consecutive overnight urine samples were collected in the autumn of 1983-1984 and the spring in 1985-1986, respectively. Urinary sodium and potassium were detected and calculated for 8 hours excretion. The occurrences of cardiovascular events were recorded in 2 years interval from 1987-1988 until December 31, 2005. Participants were divided into first ratio group, second ratio group, and third ratio group based on the tertiles of sodium to potassium ratio. Cox proportional hazard regression model was used to determine the relationship between sodium to potassium ratio and risk of CVD. In addition, participants were divided into 2 subgroups by the median of overnight urinary sodium and potassium, and then combined each other for 4 subgroups including low sodium-low potassium group, low sodium-high potassium group, high sodium-low potassium group, and high sodium-high potassium group, to explore the relationship between different sodium-potassium combinations and the risk of CVD. Results: A total of 954 participants were included in the final analysis, of whom 459 (48.1%) were males. There were 318 cases in the first, second and third ratio group, respectively. There were 347 cases in low sodium-low potassium group and high sodium-high potassium group, and 130 cases in low sodium-high potassium group and high sodium-low potassium group. After a median follow-up of 18.6 (18.3, 19.3) years, cardiovascular events occurred in 81 participants, including 64 stroke and 20 coronary heart disease events. Multivariate analysis showed that comparing with the first ratio group, the hazard ratios (HR) in the second and the third ratio groups were 2.04 (95%CI 1.06-3.95, P=0.034) and 2.07 (95%CI 1.07-4.03, P=0.032), respectively. The CVD risk in low sodium-low potassium group was 24% higher than the low sodium-high potassium group (reference), but this result did not reach statistical significant level (P=0.685). The risks in high sodium-high potassium group (HR=3.32, 95%CI 1.26-8.76,P=0.015) and high sodium-low potassium (HR=3.04, 95%CI 1.05-8.83, P=0.041) group were both significantly increased. Conclusions: Overnight urinary sodium to potassium ratio is positively correlated with the risk of cardiovascular events. High urinary sodium plays a more important role for the increased risk of cardiovascular events than low potassium.

[Treatment outcome evaluation of different mandibular advancements using oral appliance to treat obstructive sleep apnea and hyponea syndrome: a systematic review].

OBJECTIVE: To evaluate the polysomnology results along with mandibular titrated advancement using oral appliance to treat obstructive sleep apnea and hyponea syndrome (OSAHS). METHODS: Several electronic databases (PubMed, Embase, Cochrane Library, CNKI, VIP, and Wanfang) were systematically searched up to September 2015. There was no restriction of language or source of information. All randomized clinical trials (RCT) and before-after trials (BAT) comparing at least two different mandibular advancements were included. Two independent reviewers selected the studies, extracted data and evaluated risk of bias by quality assessment. Data were pooled using a fixed-effects model, and the summary effect measure was calculated by risk ratio (RR) and 95%CI. Meta-analysis was performed using RevMan 5.3 software. RESULTS: Two RCTs and five BATs were included in the review. Among the five BATs, two of them were randomized, while the other three were not. Outcomes including apnea hypopnea index (AHI), oxygen desaturation index (ODI), success rate (reduction of AHI or ODI >50%), normalization rate (AHI or ODI<10/h) were assessed in this review. Based on the trial design and quality assessment, four studies were included for meta-analysis. No significant difference in the success rate was found between the group with 50% of the maximal mandibular advancement (MMA) and the group with 75% of MMA [I2=0%, RR=0.93, with 95%CI (0.80, 1.09)]. No significant difference in the normalization rate was found between the 50% of MMA and 75% of MMA groups [I2=45%, RR=0.85, with 95%CI (0.68, 1.06)]. Subgroup analysis displayed that the severity of OSAHS before treatment was a potential factor affecting the normalization rate. CONCLUSION: Based on current available evidence, the success rate and normalization rate for treating OSAHS in the patients with 75% MMA were not found to be significantly higher than those with 50% MMA. Due to small simple size in this meta-analysis, the results of the present study should be interpreted with caution. Further prospective studies are needed to strengthen the evidence.

[Efficacy of oral appliance therapy of obstructive sleep apnea and hypopnea syndrome in different periods of treatment].

OBJECTIVE: To investigate the long-term efficacy of oral appliance treating of obstructive sleep apnea and hypopnea syndrome (OSAHS) in different periods of treatment. METHODS: A total of 55 patients were included in the study. Patients were all diagnosed with OSAHS by overnight polysomnography and all received oral appliance (OA) as the therapy. The OA positioned the mandible at 60%-70% of the maximal mandible advancement position and created a 4-5 mm incisor separation. The patients were instructed to wear the appliance during sleep, 6-8 hours per day, for 5-7 days per week. They were divided into four groups by the period of treatment, including less than 1 year group; 1-2 years group; 2-6 years group and 6-9 years group. The polysomnographic study was used to investigate the efficacy of the four groups. The outcome measures included the score on the apnea-hypopnea index (AHI), the longest apnea time and the lowest oxygen saturation (LSaO2) levels during an overnight sleep. RESULTS: The AHI decreased significantly in all the four groups. The less than 1 year group decreased from 24.50 (14.65, 54.05) to 7.40 (2.12,10.00) events/h (P<0.001); The 1-2 years group decreased from 19.50 (12.15, 39.23) to 1.80 (0.70, 6.58) events/h (P=0.001); The 2-6 years group decreased from 25.00 (11.41, 42.60) to 4.50 (1.35, 7.90) events/h (P=0.001); The 6-9 years group decreased from 26.2 (16.95, 47.45) to 4.00 (1.90, 26.70) events/h (P=0.043). The longest apnea decreased significantly in less than 1 year group, 1-2 years group and 2-6 years group. The longest apnea decreased from 57.00 (37.70, 61.50) to 25.00 (15.90, 33.50) seconds (P<0.001) in the less than 1 year group, from 41.00 (25.50, 62.26) to 13.10 (0.00, 22.10) seconds (P=0.001) in the 1-2 year group and from 42.50 (30.35, 58.15) to 15.60 (0.00, 28.10) seconds (P=0.003) in the 2-6 year group. The LSaO2 levels increased significantly in the less than 1 year group and 2-6 years group. The LSaO(2) levels rose significantly in the less than 1 year group, from 74.18%±7.96% to 84.06%±7.67% (P=0.001), and in the 2-6 years group, from 76.71%±10.98% to 84.06%±4.64% (P=0.006), The LSaO2 levels did not increase significantly in the 1-2 years and 6-9 years groups. Kruskal-Wallis test showed that there were no statistically significant differences in the AHI, longest apnea time and LSaO(2) in 4 the groups. CONCLUSION: The oral appliance is an effective therapy for patients with OSAHS in the long-term treatment. However, it's recommended to make appointments with patients as a follow-up supervision whether there is any efficacy decrease. And the oral appliance should be replaced if necessary.

Downregulation of ZBTB24 hampers the G0/1- to S-phase cell-cycle transition via upregulating the expression of IRF-4 in human B cells.

It has been recently identified that loss-of-function mutations in the uncharacterized gene ZBTB24 (zinc finger and BTB domain-containing 24) cause ICF2 (immunodeficiency, centromeric instability and facial anomalies syndrome 2) with immunological characteristics of greatly reduced serum antibodies and circulating memory B cells. ZBTB24 belongs to the large ZBTB family of transcriptional repressors with members like B-cell lymphoma 6 (BCL-6; ZBTB27) playing critical roles in B-cell functions. Given the genotype-phenotype correlation analyses in ICF2 patients and the high expression of ZBTB24 in human B cells, we, in the present study, investigated the function of ZBTB24 in human B-cell line Raji cells. Knockdown of endogenous ZBTB24 by small hairpin RNAs results in a significantly reduced proliferation through blocking the G0/1- to S-phase cell-cycle progression, but not apoptosis induction. Moreover, downregulation of ZBTB24 increases the expression of IRF-4 (interferon regulatory factor 4) and Blimp-1 (B lymphocyte-induced maturation protein 1), two crucial factors involved in the proliferation and differentiation of B cells. Importantly, ZBTB24 exerts these functions independent of BCL-6 as it does not affect the expression and function of BCL-6. Our study thus not only provides a molecular explanation for the B-cell and antibody defects observed in ZBTB24-deficient ICF2 patients, but also indicates that ZBTB24 represents a novel transcriptional factor essentially involved in human B-cell functions.

A network approach predicts NFKBIA and BIRC3 as pathogenic genes in childhood asthma.

This study aimed to predict pathogenic genes of childhood asthma based on molecular interaction networks and gene expression data. Known pathogenic genes identified from the human protein-protein interaction network were denoted as seed genes, and were included in network A. We extracted sub-network B (pathogenic network), which consisted of genes that interacted with at least two seed genes. We assigned a weight to select the pathogenic genes from this network according to its interactions and co-expressions with the seed genes. We also conducted ClusterONE analysis for the pathogenic network, and determined the statistical significance of the predicted clusters through a significance score (SS). Lastly, we investigated the biological pathways of the seed and candidate genes based on information obtained from the KEGG database. In network A, we identified 172 interactions and 125 genes that interacted with seed genes. In the pathogenic network, we found 51 genes and 102 interactions. The top 10 candidate genes with high weight scores were recorded. The SS of the predicted clusters demonstrated that 3 gene clusters were statistically relevant for childhood asthma. Pathway analysis showed that the seed genes and the top 10 candidate genes were significantly enriched in the same three biological processes. NFKBIA and BIRC3, which were involved in all three biological processes, may therefore be pathogenic genes. Using the network approach, we predicted that the pathogenic genes NFKBIA and BIRC3 are associated with childhood asthma. This information can provide guidelines for future experimental verification of childhood asthma.

[Craniofacial anatomical Characteristics of patients with catathrenia].

Objective: To analyze whether the upper airway of patients with catathrenia has obstructive manifestations using nasal resistance, craniofacial, and upper airway imaging methods, which could benefit the exploration of the etiology and treatment options. Methods: From August 2012 to September 2019, a total of 57 patients with catathrenia in the Department of Orthodontics at Peking University Hospital of Stomatology were included in the study, including 22 males and 35 females, aged (31.1±10.9) years, with a body mass index of (21.7±2.7) kg/m2. All the patients were diagnosed by full-night polysomnography at the Sleep Division, Peking University People's Hospital, of which 10 patients were combined with obstructive sleep apnea hypopnea syndrome (OSAHS). The median groaning index of patients was 4.8 (1.8, 13.0) events/h. Nasal resistance and cone-beam CT were conducted on the patients, and measurements were performed on the craniofacial structures, upper airway, and surrounding soft tissues, compared with non-snoring normal occlusion individuals' references published by the same research team (144 college students recruited at Peking University and 100 non-snoring young adults with normal occlusion recruited at six universities in Beijing). Results: The total nasal resistance of patients with catathrenia was (0.26±0.08) Pa·cm-3·s-1. The patients had overall well-developed mandibular hard tissues. However, the patients were found with increased FH/BaN (steep anterior cranial base plane), increased MP/FH (forward rotation of the mandible); increased U1/NA and L1/MP (proclined upper and lower incisors). The sagittal diameter of the velopharynx [(19.2±4.5) mm] was significantly larger than the normal reference (t=8.44, P<0.001), while the sagittal diameter at the hypopharynx [(17.4±6.4) mm] was statistically smaller than the normal reference (t=-2.79, P=0.006). Catarhrenia patients combined with OSAHS presented longer soft palate, tongue, and lower hyoid bone than those with primary catathrenia. Conclusions: In patients with catathrenia, the overall craniofacial characteristics are well-developed skeletal structures, lower nasal resistance, proclined upper and lower incisors, wide upper sagittal development of the upper airway and narrow hypopharynx. Groaning sounds might be related to the narrowing of the hypopharynx during sleep.

Single nucleotide polymorphisms of the bovine VEGF-B gene and their associations with growth traits in the Nanyang cattle breed.

PCR-SSCP and DNA sequencing methods were applied to reveal single nucleotide polymorphisms (SNPs) in the bovine VEGF-B gene in 675 samples belonging to three native Chinese cattle breeds. We found 3 SNPs and a duplication NC_007330.5: g. [782 A>G p. (Gly112 =) (;) 1000-1001dup CT (;) 1079 C>T (;) 2129 G>A p. (Arg184Gln)]. We also observed a statistically significant association of the polymorphism (1000-1001dup CT) in intron 3 of the VEGF-B gene with the body weight of the Nanyang cattle (p < 0.05). This polymorphisms of VEGF-B gene need to be verified among a larger cattle population before it can be identified as a marker for bovine body weight.

Lack of association of single nucleotide polymorphisms of the bovine Flt-1 gene with growth traits in Chinese cattle breeds.

We analyzed 20 exons, with their intron-exon boundaries, of the bovine Flt-1 gene, using a strategy combining PCR amplification and single-strand conformational polymorphism analysis (PCR-SSCP), followed by nucleotide sequence analysis, in 675 cattle. We then looked for associations between polymorphisms and growth traits. Twelve novel SNPs (ss#184956516, ss#184956517, ss#184956518, ss#184956519, ss#251343993, ss#251343994, ss#251343995, ss#251343996, ss#251343997, ss#251343998, ss#251343999, and ss#251344000) were detected in the bovine Flt-1 gene in all three breeds. We observed no significant associations between these polymorphisms and birth weight, body weight and average daily gain during different growth periods (6, 12, 18, and 24 months old) (P > 0.05), or in body height, body length, heart girth, or height at the hip in Nanyang cattle breeds.

Elevated expression of transmembrane IL-15 in immune cells correlates with the development of murine lupus: a potential target for immunotherapy against SLE.

Presentation in trans by the Interleukin-15 receptor alpha chain (IL-15Ralpha) has been suggested as the main mechanism for IL-15 anchoring to the cell surface, but it is also evident that IL-15 can exist as a transmembrane protein. We herein demonstrate that replacement of the first 41 residues of human IL-15 (hIL-15) with Igkappa chain leader sequence resulted in secretion of most of the recombinant hIL-15 expressed in transfectant cells, thus identifying the transmembrane region of IL-15. A fusion protein (hIL-15Ralpha-Fc) between the extracellular domain of hIL-15Ralpha and the Fc fragment of IgG1 was prepared and shown to be able to bind with transmembrane IL-15 (tmIL-15). The level of tmIL-15 expression in macrophages, activated T cells and B cells from 6-month-old BXSB male mice, an animal model for systemic lupus erythematosus (SLE), was significantly increased compared with that from BXSB females or young males. In addition, hIL-15Ralpha-Fc was able to block the T cell stimulating and anti-apoptotic effect of the tmIL-15-positive BXSB macrophages in vitro. Intravenous administration of hIL-15Ralpha-Fc reduced the titre of autoantibodies against dsDNA and also proteinuria in aged BXSB males, implying that neutralization of IL-15 activity in vivo may be an effective way of treating SLE.

Elevated levels of serum antibodies against Saccharomyces cerevisiae mannan in patients with systemic lupus erythematosus.

This study was undertaken to investigate whether levels of anti-Saccharomyces cerevisiae mannan antibodies (ASCMAs), a serological marker for Crohn's disease, seronegative spondyloarthritis and Behcet's disease, also correlate with systemic lupus erythematosus (SLE) in humans. Serum samples from healthy volunteers (n = 152) and patients with SLE (n = 40) were compared for ASCMA-IgA, -IgG and -IgM levels using enzyme linked immunosorbent assays. ASCMA-IgG, but not IgM and IgA, prevalence was significantly raised in active SLE patients (57.5%) compared with healthy controls (8.5%). ASCMA-IgG levels in SLE patients during remission were relatively lower, indicating a possible correlation with disease activity. These results differ from a previous study, which did not detect a difference between ASCMA levels in SLE patients and healthy control. It remains to be evaluated whether elevated ASCMA-levels are common to all rheumatic disorders.

[Effect of oral appliance treatment on age-related changes of sleep respiratory function in patients with obstructive sleep apnea hypopnea syndrome].

Objective: The severity of obstructive sleep apnea hypopnea syndrome (OSAHS) has a tendency to increase with age. The purpose of this study was to explore whether oral appliance (OA) treatment can block this age-related change. Methods: This study was a retrospective study. Fifteen patients (12 males,3 females) of OSAHS treated with OA were selected as treatment group,with an average age of (47.44±10.00) years and initial body mass index (BMI) of (26.31±3.33) kg/m(2). The follow-up length was 54 [22, 100] months. Nineteen patients (13 males,6 females) with untreated OSAHS served as controls, with an average age of (45.00±9.26) years and initial BMI of (25.53±2.58) kg/m(2),and the follow-up length was 35 [26,63] months. There were no significant differences in terms of gender,age,initial BMI, apnea hypopnea index(AHI), and follow-up length between the two groups. Polysomnography(PSG) data for the two groups were compared to observe the sleep respiratory function changes as aging by Wilcoxon test. Results: There was no significant difference in BMI of the treatment group and the control group at the time of follow-up, with BMI of treatment group from (26.31±3.33) kg/m(2) to (25.67±3.65) kg/m(2),Z=-1.223,P=0.221; and BMI of control group from (25.53±2.58) kg/m(2) to (25.12±2.72) kg/m(2),Z=-1.193,P=0.233. There was no significant difference in the change of AHI within the treatment group, from 26.20 [11.50, 52.98]/h to 23.10 [16.00, 45.00]/h, Z=-0.284, P=0.776; AHI in the control group was higher than that at the first visit, and the AHI increased from 15.00 [10.72, 28.90]/h to 31.10 [13.00, 41.80]/h, Z=-3.481, P<0.001. The longest apnea duration was not statistically different in the treatment group, from 60.00 [56.40, 74.00] s to 63.00 [52.00, 77.00] s, Z=-0.345, P=0.730; the longest apnea duration in the control group increased from 42.00 [34.00, 56.70] s to 46.00 [37.00,62.00] s,Z=-2.274,P=0.023. There was no significant difference in the lowest blood oxygen saturation of the treatment group and the control group, with the treatment group from 72.47%±12.69% to 72.73%±17.59%, Z=-0.597, P=0.550; and the control group from 78.21%±9.30% to 76.42%±12.17%, Z=-0.153, P=0.879. Conclusion: Symptoms of sleep apnea in OSAHS patients tend to increase with age,and oral appliance treatment may have the effect of slowing down this age-related worsening effect.