[Research progress on differential diagnosis of thalassemia trait and iron deficiency anemia by blood erythrocyte parameters].

Thalassemia trait is an autosomal recessive genetic disease, which is a hemolytic anemia caused by disturbance of erythrocyte hemoglobin production caused by gene mutation or deletion. Iron deficiency anemia is caused by a lack of iron in the body due to an imbalance between the demand and supply of iron. The laboratory manifestations of both are microcytic hypochromic anemia, but the treatment schemes are completely different, and it is difficult to distinguish them from the results of blood count. Erythrocyte parameters can be used to establish a formula or model to differentiate them, which can achieve the purpose of early screening, early diagnosis and early treatment,preventing the occurrence of severe anemia and providing a scientific basis for the thalassemia and iron deficiency anemia prevention. This article will review the research progress of using erythrocyte parameters to distinguish thalassemia trait with iron deficiency anemia.

[Correlation between first tarsometatarsal joint sagittal mobility and hallux valgus combined with transfer metatarsalgia].

Objective: To investigate the correlation between the first tarsometatarsal joint (TMT1) sagittal mobility and hallux valgus (HV) combined with transfer metatarsalgia (TM). Methods: The weight-bearing CT (WBCT) imaging data of 111 HV patients (167 feet) who were treated at the Foot and Ankle Surgery Center, Beijing Tongren Hospital Affiliated to Capital Medical University from January 2018 to January 2020 were retrospectively analyzed. The patients underwent PedCAT WBCT scans of both feet, and the hallux valgus angle (HVA), intermetatarsal angle (IMA), plantar distance (PD), medial cuneiform-first metatarsal angle (CMA) and metatarsal protrusion distance (MPD) were measured using CubeVue software. PD and CMA were signs of TMT1 instability. Visual analogue scale (VAS) and foot and ankle ability measures (FAAM) scores were obtained. The patients were divided into TM group and non-TM group according to the presence of metatarsalgia. The TM group and the non-TM group were compared in terms of HVA, IMA, PD, CMA, MPD, VAS and FAAM. Correlations between PD, CMA and HVA, IMA, VAS, FAAM were analyzed using Spearman correlation. Results: Total of 111 cases were included in this study, there were 35 males and 76 females with a mean age of (57.7±14.1) years. The average values of HVA (37.9°±8.6°), IMA (17.9°±2.6°), CMA (2.1°±0.3°) and PD [(1.8±0.4) mm] in TM group were all significantly higher than those in the non-TM group [HVA (32.5°±9.1°), IMA (15.1°±3.4°), CMA (1.7°±0.3°) and PD (1.6±0.2) mm] (All P<0.001). There was no significant difference in MPD between the two groups (P=0.580). The TM group demonstrated a higher VAS score when compared with the non-TM group (P<0.001). The FAAM score of the TM group (54.1±11.8) was significantly lower than that in the non-TM group (66.2±11.4) (P<0.001). The results of Spearman correlation analysis showed that there was no correlation between PD and HVA, IMA and VAS score. There was a negative correlation between PD, CMA and FAAM score, and the difference was statistically significant (rs=-0.637, -0.254, both P<0.001); CMA was positively correlated with HVA, IMA, and VAS score (rs=0.603, 0.971, 0.269, all P<0.001). Conclusions: WBCT is helpful for the diagnosis of TMT1 sagittal instability. The severity of TMT1 sagittal instability is positively correlated with hallux valgus and TM. The TMT1 instability may play an important role in the pathogenesis of hallux valgus.

[The effect of strengthening nutrition education in the second trimester on the basis of the first trimester on blood glucose].

Objective: To explore the effect of strengthening individualized nutrition education in the second trimester based on first trimester on blood glucose. Methods: A retrospective study was conducted on 398 pregnant women aged (31.79±3.48) (23-41) years old who underwent an oral glucose tolerance test (OGTT) from October 2021 to December 2022 at Beijing Tsinghua Changgung Hospital. They were divided into two groups according to whether the women were re-visited in second trimester or not. The routine group consisted of 205 pregnant women aged between 24 and 41 (31.49±3.36) years old who only received the first trimester nutrition education and the strengthening group consisted of 193 pregnant women aged (31.92±3.97) (23-41) years old who received both the first and second trimester nutrition education. Then according to pre pregnancy body mass index (BMI), they were divided into normal (18.5 kg/m2≤BMI<24 kg/m2) and overweight (24 kg/m2≤BMI<28 kg/m2). The OGTT blood glucose level, the positive rate of gestational diabetes (GDM) and the weight gain during pregnancy were compared between the two groups with different BMI, in order to analyze the effect of strengthening nutrition education in the second trimester of pregnancy on blood glucose. Results: The differences between the two groups were not statistically significant in terms of the pregnant women's age, proportion of pregnant women aged≥35, proportion of pre-pregnancy BMI and overweight, parity and early pregnancy blood glucose (all P>0.05). The blood glucose levels of OGTT at 0, 1, and 2 hour were (4.57±0.37), (8.41±1.70), and (7.28±1.51) mmol/L, respectively, lower than those in the routine group [(4.74±0.48), (9.44±1.55), and (8.27±1.58) mmol/L, respectively, all P<0.001]. The positive rate of GDM in the strengthening group was 35.23% (68/193), which was lower than that in the routine group (91.71%, 188/205) (P<0.001). After the BMI stratification, the OGTT blood glucose levels and the positive rate of GDM in the strengthening group were still lower than those in the routine group (all P<0.05). The weight gain with normal BMI in the early pregnancy in routine group was higher than that in the strengthening group (P=0.003), but there was no significant statistical difference in weight gain of overweight pregnant women at different gestational weeks (all P>0.05). Conclusion: Strengthening a nutrition education about second trimester for pregnant women in the early stages of pregnancy can effectively improve blood glucose levels and reduce the positive rate of GDM.

[The value of machine learning models based on biparametric MRI for diagnosis of prostate cancer and clinically significant prostate cancer].

Objective: To evaluate the value of machine learning (ML) models based on biparametric magnetic resonance imaging (bpMRI) for diagnosis of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). Methods: A total of 1 368 patients, aged from 30 to 92 (69.4±8.2) years, from 3 tertiary medical centers in Jiangsu Province were retrospectively collected from May 2015 to December 2020, including 412 cases of csPCa, 242 cases of clinically insignificant prostate cancer (ciPCa) and 714 cases of benign prostate lesions. The data of center 1 and center 2 were randomly divided into training cohort and internal testing cohort at a ratio of 7∶3 by random number sampling without replacement using Python Random package, and the data of center 3 were used as the independent external testing cohort. The training cohort includs 243 cases of csPCa, 135 cases of ciPCa and 384 cases of benign lesions, the internal testing cohort includs 104 cases of csPCa, 58 cases of ciPCa and 165 cases of benign lesions, and the external testing cohort includs 65 cases of csPCa, 49 cases of ciPCa and 165 cases of benign lesions. The radiomics features were extracted on T2-weighted imaging, diffusion-weighted imaging and apparent diffusion coefficient map, and optimal radiomics features were selected by using Pearson correlation coefficient method and analysis of variance. The ML models were built using two ML algorithms, including support vector machine and random forest (RF) and were further tested in the internal testing cohort and external testing cohort. Finally, the PI-RADS scores evaluated by the radiologists were adjusted by the ML models which had superior diagnostic performance, namely adjusted PI-RADS. The receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the ML models and PI-RADS. DeLong test was used to compare the areas under curve (AUC) of models with those of PI-RADS. Results: For PCa diagnosis, in internal testing cohort, the AUC of ML model using RF algorithm and PI-RADS were 0.869 (95%CI: 0.830-0.908) and 0.874 (95%CI: 0.836-0.913), respectively, and the difference between the model and PI-RADS did not reach to the statistical significance (P=0.793). In the external testing cohort, the AUC of model and PI-RADS were 0.845 (95%CI: 0.794-0.897) and 0.915 (95%CI: 0.880-0.951), respectively, and the difference was statistically significant (P=0.01). For csPCa diagnosis, the AUC of ML model using RF algorithm and PI-RADS were 0.874 (95%CI: 0.834-0.914) and 0.892 (95%CI: 0.857-0.927), respectively, in internal testing cohort, and the difference between the model and PI-RADS was not statistically significant (P=0.341). In the external testing cohort, the AUC of model and PI-RADS were 0.876 (95%CI: 0.831-0.920) and 0.884 (95%CI: 0.841-0.926), respectively, and the difference between the model and PI-RADS was not statistically significant (P=0.704). When PI-RADS assessment was adjusted with the assistance of ML models, the specificities increased from 63.0% to 80.0% in the internal testing cohort and from 92.7% to 93.3% in the external test group in diagnosing PCa. In diagnosing csPCa, the specificities increased from 52.5% to 72.6% in the internal testing cohort and from 75.2% to 79.9% in the external testing cohort. Conclusions: The ML models based on bpMRI showed comparable diagnostic performance to PI-RADS assessed by senior radiologists and achieved good generalization ability in both diagnosing PCa and csPCa. The specificities of the PI-RADS were improved by ML models.

[Analysis of dynamic functional connectivity states and influencing factors of brain network in male patients with obstructive sleep apnea].

Objective: To analyze dynamic functional connectivity (dFNC) states and influencing factors of brain network in male patients with obstructive sleep apnea (OSA). Methods: A total of 111 male patients diagnosed with obstructive sleep apnea or presenting with simple snoring, who visited the Sleep Clinic at the Second Affiliated Hospital of Soochow University between August 2020 and December 2021, were prospectively selected for this study. General information was collected, and polysomnography (PSG) was performed. Based on the oxygen desaturation index (ODI), the participants were divided into three groups: primary snoring group (ODI<5 events/hour, n=34), mild to moderate OSA group (5 events/hour≤ODI<30 events/hour, n=43), and sever OSA group (ODI≥30 events/hour, n=34). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). Resting-state functional magnetic resonance imaging (fMRI) data were collected and preprocessed. dFNC matrices were constructed using a sliding time window approach. The number of dFNC states was determined using k-means clustering analysis. Three parameters, namely, fractional time (FT), mean dwell time (MDT), and number of transitions (NT), were used to characterize the temporal properties of dFNC states. Differences in the temporal properties of dFNC states among the groups were compared. The correlations between temporal properties and PSG parameters, as well as MoCA and ESS scores, were further analyzed. Multiple stepwise linear regression analysis was performed to identify the influencing factors of the temporal properties of dFNC states. Results: The age of the patients was (40.2±8.6) years (range: 25-65 years). There were no significant differences in age, smoking history and alcohol history, and MoCA scores among the three groups (all P>0.05). Three dFNC states were extracted through k-means clustering analysis: state 1, characterized by strong connections within the visual and sensorimotor networks with a frequency of 31.7% (4 611/14 541); state 2, characterized by strong connections within the default mode network, attention network, and other cognitive networks, with the lowest frequency of 22.1% (3 213/14 541); state 3, characterized by weaker connections across the whole brain, with the highest frequency of 46.2% (6 717/14 541). The FT [0.28 (0.05, 0.35) vs 0.39 (0.26, 0.53)] and MDT [8.20 (4.35, 12.54) vs 11.68 (8.50, 16.69)] of state 2 in the sever OSA group were lower than those in the primary snoring group (both P<0.05), while there were no significant differences in the temporal properties of states 1 and 3 among the three groups (all P>0.05). The FT and MDT of state 2 were correlated with body mass index (BMI), apnea-hypopnea index (AHI), ODI, and minimum oxygen saturation (MinSaO2) (FT: r values were -0.218, -0.230, -0.249, 0.198, respectively; MDT: r values were 0.269, -0.253, -0.265, 0.209, respectively; all P<0.05). There were no significant correlations between the temporal properties and MoCA or ESS scores (all P>0.05). ODI was found to be an influencing factor for the temporal properties of state 2 (FT: ß=-0.225, 95%CI:-0.227 to -0.223; MDT: ß=-0.241, 95%CI:-0.289 to -0.195). Conclusions: Male patients with OSA exhibit alterations in specific temporal properties of brain network dynamic functional connectivity, which are associated with nocturnal oxygen parameters. This may be one of the mechanisms underlying brain functional damage in patients with OSA.

[Genetic diagnosis of microcephaly].

Objective: To explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly. Methods: A total of 9 cases of microcephaly fetuses diagnosed by prenatal ultrasound or children with microcephaly diagnosed after birth were selected from the Sixth Affiliated Hospital of Guangzhou Medical University from January 2014 to August 2022.Karyotype analysis and/or CMA were used to detect. The cases with negative karyotype analysis and CMA results were further sequenced by trio-based WES (Trio-WES). Then the coding genes contained in the pathogenic copy number variation (CNV) fragments were analyzed by gene ontology (GO) enrichment. The genes related to the development of the central nervous system contained in the pathogenic CNV and the pathogenic genes found by Trio-WES were combined for gene interaction network analysis. Results: In this study, 9 cases of microcephaly were recruited, with the time of diagnosis ranged from 23 weeks of gestation to 7 years after birth, and the head circumference of fetus or children ranged from 18.3 to 42.5 cm (-7SD to -2SD). Karyotype analysis was detected in all 9 cases and no abnormality result was found. Eight cases were detected by CMA, and one abnormal was found. Five cases were detected by Trio-WES, and two cases were detected with likely pathogenic genes. The GO enrichment analysis of the coding gene in the 4p16.3 microdeletion (pathogenic CNV) region showed that: in biological process, it was mainly concentrated in phototransduction, visible light; in terms of molecular function, it was mainly concentrated in fibroblast growth factor binding; in terms of cell components, it was mainly concentrated in rough endoplasmic reticulum. Gene interaction network analysis suggested that CDC42 gene could interact with CTBP1, HTT and ASPM gene. Conclusions: CMA could be used as a first-line detection technique for microcephaly. When the results of chromosome karyotype analysis and/or CMA are negative, Trio-WES could improve the detection rate of pathogenicity of microcephaly.

[Analysis on missed diagnosis or misdiagnosis of anomalous origin of left coronary artery from pulmonary artery by echocardiography from one single medical center].

Objectives: To analyze the reasons of missed diagnosis or misdiagnosis on anomalous origin of left coronary artery from pulmonary artery (ALCAPA) by echocardiography. Methods: This is a retrospective study. Patients with ALCAPA who underwent surgical treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from August 2008 to December 2021 were included. According to the results of preoperative echocardiography and surgical diagnosis, the patients were divided into confirmed group or missed diagnosis/misdiagnosis group. The results of preoperative echocardiography were collected, and the specific echocardiographic signs were analyzed. According to the experience of the doctors, the echocardiographic signs were divided into four types, namely clear displayed, vague/doubtful displayed, no display and no notice, and the display rate of each sign was calculated (display rate=number of clearly displayed cases/total number of cases×100%). By referring the surgical data, we analyzed and recorded the pathological anatomy and pathophysiological characteristics of the patients, and the rate of missed diagnosis/misdiagnosis of echocardiography in patients with different characteristics was compared. Results: A total of 21 patients were enrolled, including 11 males, aged 1.8 (0.8, 12.3) years (range 1 month to 47 years). Except for one patient with anomalous origin of left anterior descending artery, the others were all originated from the main left coronary artery (LCA). There were 13 cases of ALCAPA in infant and children, and 8 cases of adult ALCAPA. There were 15 cases in the confirmed group (diagnostic accuracy was 71.4% (15/21)), and 6 cases in the missed diagnosis/misdiagnosis group (three cases were misdiagnosed as primary endocardial fibroelastosis, two cases were misdiagnosed as coronary-pulmonary artery fistula; and one case was missed diagnosis). The working years of the physicians in the confirmed group were longer than those in the missed diagnosis/misdiagnosed group ((12.8±5.6) years vs. (8.3±4.7) years, P=0.045). In infants with ALCAPA, the detection rate of LCA-pulmonary shunt (8/10 vs. 0, P=0.035) and coronary collateral circulation (7/10 vs. 0, P=0.042) in confirmed group was higher than that in missed diagnosis/misdiagnosed group. In adult ALCAPA patients, the detection rate of LCA-pulmonary artery shunt was higher in confirmed group than that in missed diagnosis/misdiagnosed group (4/5 vs. 0, P=0.021). The missed diagnosis/misdiagnosis rate of adult type was higher than that of infant type (3/8 vs. 3/13, P=0.410). The rate of missed diagnosis/misdiagnosis was higher in patients with abnormal origin of branches than that of abnormal origin of main trunk (1/1 vs. 5/21, P=0.028). The rate of missed diagnosis/misdiagnosis in patients with LCA running between the main and pulmonary arteries was higher than that distant from the main pulmonary artery septum (4/7 vs. 2/14, P=0.064). The rate of missed diagnosis/misdiagnosis in patients with severe pulmonary hypertension was higher than that in patients without severe pulmonary hypertension (2/3 vs. 4/18, P=0.184). The reasons with an echocardiography missed diagnosis/misdiagnosis rate of≥50% included that (1) the proximal segment of LCA ran between the main and pulmonary arteries; (2) abnormal opening of LCA at the right posterior part of the pulmonary artery; (3) abnormal origin of LCA branches; (4) complicated with severe pulmonary hypertension. Conclusions: Echocardiography physicians' knowledge of ALCAPA and diagnostic vigilance are critical to the accuracy of diagnosis. Attention should be paid to the pediatric cases with no obvious precipitating factors of left ventricular enlargement, regardless of whether the left ventricular function is normal or not, the origin of coronary artery should be routinely explored.

Difference responses of soil fungal communities to cattle and chicken manure composting application.

AIMS: Cattle and poultry manure composting are often applied on agricultural lands but the fungal community composition before and after application in soils is still unclear. This study describes soil fungal diversity after manure applications contribute to the correct resource use of livestock and poultry manures. METHODS AND RESULTS: Fresh manure samples were obtained from 10 beef cow farms and 12 egg-laying poultry farms at five distinct phases of rearing. Surface soil samples were collected from vegetable plots within the farms after manure application at 15, 30 and 45 t hm-2 . Using high-throughput sequencing techniques, the ITS region was used to describe soil fungus populations. The fungal OTUs, Chao1 and ACE of cattle manure were relatively higher in the fattening stage (>12 months), the OTUs and ACE of chicken manure were the highest in the initial laying stage (16-24 weeks). The fungal diversity indices of vegetable soils had no linear change after cow or chicken manure application compared with the control. Ascomycota (84.7% of total sequences), Neocallimastigomycota (9.69%) and Basidiomycota (4.6%) were the dominant phyla in cattle manure. Ascomycota (88.9%) also predominated in chicken manure followed by Basidiomycota (8.9%). Following both cattle and chicken manure applications, the abundance of Ascomycota decreased, whereas Basidiomycota and Chytridiomycota increased in the soils. None of the dominant genus increased or decreased linearly with the increase of cattle and chicken composting application rate. The fungal-dominant genera of the soils with and without manure composting application were mostly affected by soil pH and EC than manure. Pearson's correlation analysis revealed that organic matter, Cu and Hg contents were strongly linked to the fungal diversity and the abundance of specific taxa in cattle manure. In chicken manure, OM, TN and Zn were major factors controlling the fungal diversity and community composition. Soil pH, EC and Cu, Zn, Cd, Hg and As content had pronounced effects on the beneficial and pathogenic genus in soil with and without manure composting. Beneficial fungal genus such as Aspergillus, Plectosphaerella, Acremonium, Meyerozyma and fungal pathogenic such as Fusarium, Cladosporium, Verticillium were sensitive to properties (EC, pH, OM) and heavy metals (Cu, Zn, Hg) contents of the environment relatively. This study can serve as an applicable contribution helping in farms management (especially to cattle and poultry breeding) and improving their resource use of livestock and poultry manures. CONCLUSIONS: Soil heterogeneity rather than manure determines fungal communities in the vegetable fields, but we can encourage the sensible use of cattle and chicken manures in agroecosystems. SIGNIFICANCE AND IMPACT OF THE STUDY: This study will help farmers regulate the dosage of feed components which can increase the number of beneficial fungal genus or reduce the number of pathogenic fungal genus, improve their resource use of livestock and poultry manures and encourage the sensible use of cattle and chicken manures in agroecosystems.

Molecular typing and epidemiology profiles of human adenovirus infection among children with severe acute respiratory infection in Huzhou, China.

Human adenoviruses (HAdVs) are prevalent worldwide and are a common cause of respiratory tract infection in people of all ages. However, little is known about HAdV infection among children with severe acute respiratory infection (SARI). The present study retrospectively analysed the molecular typing and epidemiological characteristics of HAdV-positive samples from children with SARI from January 2017 to December 2021 in Huzhou. The results showed that 89 (8·27%) of 1078 SARI paediatric patients were positive for HAdVs. Children <5 years of age accounted for 87·64% of the positive cases. The peak seasons for HAdV infection were the first quarter and the fourth quarter. In addition, HAdV-B and HAdV-C were circulating among paediatric patients with SARI, of which the B3 genotype (n = 30, 51·72%) was the most prevalent and was detected every year, indicating that B3 is the main epidemic strain in the Huzhou area, followed by C1 (n = 9, 15·52%), C2 (n = 7, 12·07%) and B7 (n = 5, 8·62%). These findings provide a benchmark for future epidemiology and prevention strategies for HAdVs.

[Kawasaki disease complicated with mild encephalitis/encephalopathy with a reversible splenial lesion: A case report and literature review].

We reported a pediatric case of Kawasaki disease complicated with mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) from Beijing Tsinghua Changgung Hospital. The clinical data were retrospectively analyzed and the related literature was reviewed. The clinical features, treatment and prognosis of the disease were summarized to improve recognition of Kawasaki disease complicated with MERS. A 7-year-old boy was diagnosed with Kawasaki disease due to continuous high fever for 6 d, accompanied by strawberry tongue, conjunctival congestion, erythema-like hyperemia rash, and cervical enlarged lymph nodes. And treatment was started with intravenous immunoglobulin (IVIG: 2 g/kg) and oral aspirin [40 mg/(kg·d)]. Twenty-four hours after the treatment of IVIG, the patient' s fever persisted and in addition he developed headache and drowsiness. His cranial magnetic resonance imaging (MRI) demonstrated a localized lesion in the splenium of the corpus callosum with high intensity signal on diffusion-weighted images (DWI) and T2-weighted, and low intensity signal on apparent diffusion coefficient (ADC) and T1-weighted. Based on these findings, he was diagnosed with MERS-complicated Kawasaki disease. Methylprednisolone [2 mg/(kg·d)] treatment was started intravenously, and within several hours he was afebrile and the neurological symptoms disappeared. A follow-up MRI was conducted after 1 week was normal. He was discharged without any neurological sequelae and coronary artery lesions. A total of 12 qualified foreign literature were retrieved, with no Chinese literature searched. Seventeen children were reported, the median age was 6.5 years (range: 1-14 years), among them 11 cases were children over 5 years old, and 4 cases were complicated with coronary artery lesions. All children had neurological symptoms, such as consciousness disorder, visual hallucination or convulsion. MRI conformed to MERS imaging changes. After active treatment, the neurological manifestations and radiological abnormalities completely disappeared, leaving no neurological sequelae. Kawasaki disease complicated with MERS had not been reported in China by now. Literature that identified Kawasaki disease complicated with MERS mostly occurred in children over 5 years old. Cranial MRI examination is helpful for early diagnosis. Timely treatment can reverse MERS in a short time, without neurological sequelae left.

[Diagnostic values of urinary citrate for kidney stones in patients with primary gout].

OBJECTIVE: To evaluate the relationship between 24 h urinary ion content and kidney stones, and to explore the diagnostic values of kidney stone in primary gout patients. METHODS: Patients diagnosed with primary gout had ultrasound scanning of both feet and kidneys in Peking University First Hospital from Jan. 2020 to May 2021. Their clinical characteristics were compared between the positive and negative kidney stone groups, and the relationship between kidney stone and urinary ion composition were analyzed. Risk factors of kidney stone were analyzed. The explored diagnostic values were evaluated for urinary oxalate and citrate according with uric acid kidney stones by dual-energy computed tomography (DECT). RESULTS: Among the 100 gouty patients, 80 patients had uric acid crystal deposition in lower joints of extremity by ultrasonography, 61 patients had kidney stone, and 34 had kidney uric acid stones by DECT. All the multiple kidney stones were proved as uric acid kidney stones by DECT. Compared with patients without kidney stone group proved by ultrasonography, patients with kidney stone had longer gouty duration [(48.7±26.6) months vs. (84.0±30.6) months, P=0.01], higher 24 h urinary oxalate [(20.1±9.6) mg vs. (28.6±20.7) mg, P=0.001] and lower 24 h urinary citrate [(506.3±315.4) mg vs. (355.7±219.6) mg, P=0.001]. Compared with the patients without kidney stone by DECT, the patients with uric acid kidney stone also had longer disease duration [(49.1±28.4) months vs. (108.3±72.2) months, P=0.001], higher 24 h urinary oxalate [(23.6±16.9) mg vs. (28.5±18.8) mg, P < 0.05], lower 24 h urinary citrate [(556.0±316.3) mg vs. (391.7±261.2) mg, P < 0.05], higher serum uric acid [(466.2±134.5) µmol/L vs. (517.2±18.1) µmol/L, P < 0.05] and higher 24 h urinary uric acid [(1 518.1±893.4) mg vs. (1 684.2±812.1) mg, P < 0.05]. Logistic regression analysis showed long gout disease duration (OR=1.229, 95%CI: 1.062-1.522, P < 0.05), high serum uric acid level (OR=1.137, 95%CI: 1.001-1.213, P=0.01), low 24 h urinary citrate (OR=0.821, 95%CI: 0.659-0.952, P=0.01) were all risk factors of kidney stones by ultrasonography. Also, long gout disease duration (OR=1.201, 95%CI: 1.101-1.437, P=0.005), high serum creatine uric level (OR=1.145, 95%CI: 1.001-1.182, P=0.04), low 24 h urinary citrate (OR=0.837, 95%CI: 0.739-0.931, P=0.02) were all risk factors of kidney uric acid stones by DECT. CONCLUSION: Long disease duration and low 24 h urinary citrate were risk factors for kidney stones.

The role of Dock2 on macrophage migration and functions during Citrobacter rodentium infection.

Dedicator of cytokinesis 2 (Dock2), an atypical guanine exchange factor, is specifically expressed on immune cells and mediates cell adhesion and migration by activating Rac and regulates actin cytoskeleton remodeling. It plays a crucial role in the migration, formation of immune synapses, cell proliferation, activation of T and B lymphocytes and chemotaxis of pDCs and neutrophils. However, in-vivo physiological functions of Dock2 have been relatively seldom studied. Our previous studies showed that Dock2-/- mice were highly susceptible to colitis induced by Citrobacter rodentium infection, and in early infection, Dock2-/- mice had defects in macrophage migration. However, the specific roles of Dock2 in the migration and functions of macrophages are not clear. In this study, we found that the expression of chemokines such as chemokine (C-C motif) ligand (CCL)4 and CCL5 and chemokine receptors such as chemokine (C-C motif) receptor (CCR)4 and CCR5 in bone marrow-derived macrophages (BMDM) of Dock2-/- mice decreased after infection, which were supported by the in-vivo infection experimental results; the Transwell experiment results showed that Dock2-/- BMDM had a defect in chemotaxis. The bacterial phagocytic and bactericidal experiment results also showed that Dock2-/- BMDM had the defects of bacterial phagocytosis and killing. Furthermore, the adoptive transfer of wild-type BMDM alleviated the susceptibility of Dock2-/- mice to C. rodentium infection. Our results show that Dock2 affects migration and phagocytic and bactericidal ability of macrophages by regulating the expression of chemokines, chemokine receptors and their responses to chemokine stimulation, thus playing an essential role in the host defense against enteric bacterial infection.

Sex-specific associations of serum insulin-like growth factor-1 with bone density and risk of fractures in Chinese patients with type 2 diabetes.

We evaluated the associations of serum insulin-like growth factor-1 (IGF-1) with bone mineral density (BMD) and risk of fractures in Chinese patients with type 2 diabetes (T2D). We found positive associations between IGF-I and BMD and negative associations between IGF-I and all three modified 10-year probabilities of MOFs and HFs in men, but not in women. INTRODUCTION: The objective was to investigate the associations of serum insulin-like growth factor-1 (IGF-1) with bone mineral density (BMD) and risk of fractures in Chinese patients with type 2 diabetes (T2D) in each gender. METHODS: This was a cross-sectional, retrospective study that included men over 50 years and postmenopausal women with T2D without medical conditions or medications known to significantly affect BMD or serum IGF-I levels. Data of IGF-1, bone metabolism markers, lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD were obtained; 10-year probability of major osteoporotic fractures (MOFs) and hip fractures (HFs) was calculated and modified with rheumatoid arthritis, femoral neck T-score, and age. Correlations of IGF-1 levels with bone metabolism and risk of fractures were statistically analyzed in men and women, respectively. RESULTS: A total of 391 patients, including 226 men and 165 women, were included. The age, serum fasting C-peptide, glycosylated hemoglobin (HbA1c), bone formation marker, and all three modified 10-year probabilities of MOFs and HFs were higher in women than those in men (all p < 0.05). The levels of 25 hydroxyvitamin D (25OHD), IGF-1, and BMD were lower in women than those in men (all p < 0.05). In men, IGF-1 was positively correlated with FN and TH BMD (FN BMD: r = 0.267, p < 0.001; TH BMD: r = 0.235, p < 0.001) and negatively correlated with all three modified 10-year probabilities of MOFs (RA-modified MOFs: r = - 0.289, p < 0.001; age-modified MOFs: r = - 0.237, p < 0.001; FN T-score-modified MOFs: r = - 0.280, p < 0.001) and HFs (RA-modified HFs: r = - 0.291, p < 0.001; age-modified HFs: r = - 0.271, p < 0.001; FN T-score-modified HFs: r = - 0.270, p < 0.001), while no significant correlations were found between serum IGF-I and BMD and three modified 10-year probability in women. CONCLUSIONS: According to this study, we found sex differences in the associations of serum IGF-1 with BMD and risk of fractures in Chinese patients with T2D. These results suggested that increasing serum IGF-1 might be a clinical target for protecting fractures in T2D, especially in men.

[Urinary retinol binding protein and ß2-microglobulin were associated with urinary albumin to creatinine ratio and renal function in hospitalized diabetic patients].

Objective: To explore the associations of urinary retinol binding protein (RBP) and ß2-microglobulin (ß2-MG) with urinary albumin to creatinine ratio (UACR) and renal function in hospitalized patients with type 2 diabetes mellitus (T2DM). Methods: A total of 1 030 Chinese patients with T2DM were included in this study. The subjects were divided into the UACR normal group (<30 mg/g), microalbuminuria group (30-300 mg/g) and macroalbuminuria group (>300 mg/g). Patients with normal UACR were further divided into two groups according to the estimated glomerular filtration rate (eGFR): the eGFR low group (<90 ml·min-1·1.73m-2) and the normal eGFR group (≥90 ml·min-1·1.73m-2). Urine RBP and ß2-MG levels among the groups were compared. Multiple linear regression analyses were applied to evaluate risk factors of urine RBP and ß2-MG. Results: In all patients (n=1 030), urine RBP and ß2-MG increased gradually with the increase of UACR across the three groups, the proportions of abnormal urine RBP (>0.7 mg/L) and ß2-MG (>370 µg/L) in these groups were 3.8%, 8.5%, 39.0% (P<0.001), and 12.9%, 26.7%, 46.8% (P<0.001), respectively. In the UACR normal group (n=788), 12.2% of the patients were with eGFR<90 ml·min-1·1.73m-2. The proportion of abnormal ß2-MG (>370 µg/L) was higher in the eGFR low group than that in the eGFR normal group (29.2% vs. 10.7%, P<0.001). Multivariate linear stepwise regression analyses were performed using natural logarithm of urine RBP or ß2-MG as dependent variable, and showed that urine RBP was independently associated with UACR (ß=0.0005, P<0.001), serum creatinine (ß=0.006, P<0.001) and glycosylated hemoglobin A1c (ß=0.050, P=0.001), and ß2-MG was independently correlated with UACR (ß=0.000 4, P<0.001), serum creatinine (ß=0.011, P<0.001), systolic blood pressure (ß=0.005, P=0.031) and fasting blood-glucose (ß=0.027, P=0.046). Conclusions: Urine RBP and ß2-MG are positively associated with high UACR and impaired renal function in T2DM patients, and these changes could occur before UACR and eGFR turned out to be abnormal. It is recommended that urine RBP and ß2-MG be detected as early as possible to identify diabetic kidney disease in patients with normal UACR and eGFR.

[Analysis of the changes and characteristics of pediatric outpatient visits in a general hospital in Beijing before and after the COVID-19 pandemic].

OBJECTIVE: To analyze the changes and characteristics of pediatric outpatient visits in a general hospital before and after the coronavirus disease (COVID-19) epidemic. METHODS: Based on the registration data of pediatric outpatient visits in the information system (HIS)of Beijing Tsinghua Changgung Hospital, from January 1 2018 to December 31 2020, aged 0 to 16 years, we analyzed the changes of outpatient visits before and after the epidemic, focusing on respiratory infection including influenza. The relationship between the outpatient visits and age and quarterly distribution were also studied. RESULTS: (1) Respiratory infection accounted for the majority of outpatient visits in 2018 and 2019 (60.6% and 60.5%, respectively). Non-respiratory infection accounted for the main proportion of outpatient visits in 2020, while respiratory infection accounted for only 47.4%. Annual respiratory infection visits, respiratory infectious diseases visits especially influenza visits all decreased significantly in 2020 compared with that in 2018 and 2019 (P < 0.05). (2)Respiratory infection visits were highest in the infant group, lowest in the school age group (P < 0.05) and highest in the fourth quarter each year. It decreased significantly in the second quarter of 2020 with statistical significance when compared with the other quarters of 2020(P < 0.05). (3)Influenza accounted for the highest proportion of respiratory infectious diseases visits in each year. It was highest in first quarter, which was significantly different from the other quarters of the year (P < 0.05). There were different distributions of influenza visits throughout 2018 and 2019, while it was only distributed in the first quarter and 99% in January in 2020. CONCLUSION: The respiratory infection and influenza visits have decreased significantly in our pediatric outpatient department after the COVID-19 epidemic, which is considered closely related to the lifestyle and personal protection after the epidemic. It is recommended that health education on respiratory infection and influenza prevention should be strengthened, especially in winter and spring, to promote the development of good respiratory and hand hygiene habits.

[Visualization analysis of relevant literature on occupational health risk assessment from 2010 to 2019].

Objective: To understand the research status of occupational health risk assessment in recent ten years. Methods: In April 2020, the literatures related to occupational health risk assessment published by CNKI and Web of Science core collection (WoSCC) databases from 2010 to 2019 were searched, and Excel 2016 software was used to organize the literature, CiteSpace 5.6.R2 software was used for visual analysis. Results: A total of 58 Chinese literatures and 407 English literatures were included. The authors of the high frequency posts were Zhang Meibian, and Alessandro Marinaccio, and the publishing institutions were mainly the National Institute for Occupational Health and Poison Control of Chinese Center for Disease Control and Prevention and Finnish Institute Occupational Health. The Chinese journal with the most articles was Chinese Journal of Industrial Hygiene and Occupational Diseases, and the English journal was Safety Science. Chinese high-frequency keywords mainly included risk assessment, occupational health, occupational exposure. English high-frequency keywords mainly included occupational health, risk, risk factor. The prominent words in Chinese literature were occupational health, coal dust, occupational hazards, occupational health and occupational disease hazards; Risk assessment, worker, exposure, heart disease, cardiovascular disease and so on were prominent words in English literature. Conclusion: The main research keywords in the field of occupational health risk assessment at home and abroad focus on occupational health and risk assessment, but the research direction and focus are slightly different.

Effect of GATA4 gene methylation on proliferation and apoptosis of SGC-7901 gastric cancer cells.

Gastric cancer (GC) remains a major cause of cancer-related deaths worldwide. GATA4 has been previously reported to exhibit functions in GC. In this study, we aimed to investigate the effect of GATA4 gene methylation on GC progression. Methylation-Sensitive High-Resolution Melting was used to detect the methylation of GATA4 promoter region in GC tissues and adjacent normal tissues, GC cell lines and GES-1 cells. The relationship between GATA4 methylation level and clinical characteristics of GC patients was analyzed. GATA4 levels in GC tissues and adjacent normal tissues, GC cell lines and GES-1 cell lines were detected, and gain-of-function was performed to investigate the role of GATA4 in GC. si-GATA4 was transfected into GES-1 cells to observe the changes of various indicators. RNA-seq detected the differentially expressed genes in SGC-7901 cells overexpressing GATA4, and western blot analysis verified their expression. GATA4 methylation rate was increased in GC tissues, and GATA4 promoter was abnormally methylated in GC cells. GATA4 methylation rate in GC tissues was related to lymph node metastasis, differentiation degree and clinical stage of GC patients. Lower expressed GATA4 was observed in GC tissues and cells. Cell proliferation rate decreased and cell apoptosis rate increased in SGC-7901 cells overexpressing GATA4. Transfecting si-GATA4 into GES-1 cells led to increased proliferation, inhibited apoptosis, and restoration of GATA4 led to decreased APC and GSK3ß levels. In conclusion, restoration of GATA4 caused by 5-Aza treatment can inhibit the proliferation and promote apoptosis of GC cells possibly via Wnt/ß-catenin signaling pathway. This study may offer new sight for GC treatment.

[Application of the superior thyroid artery peak systolic velocity in differentiating Graves' disease from autoimmune thyroiditis].

Objective: To evaluate the clinical value of the superior thyroid artery peak systolic velocity (STA-PSV) for the differential diagnosis of autoimmune thyrotoxicosis. Methods: A total of 301 patients with newly diagnosed thyrotoxicosis and without any anti-thyroid drug intervention were collected from the Department of Endocrinology and Metabolism, Peking University People's Hospital from Jan. 2015 to Oct. 2018. Among them, 241 patients were with Graves' disease (GD) and 60 patients were with autoimmune thyroiditis (AIT). STA-PSV, thyroid function and thyrotropin receptor antibody (TRAb) were determined. A multiple linear regression was used to identify factors associated with STA-PSV. A receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the discriminating ability of STA-PSV to GD. Results: STA-PSV leves in GD group were significantly higher than those in AIT group [61.00 (41.00, 86.50) cm/s vs. 34.50 (25.25, 46.00) cm/s, P<0.001]. The ROC curve analysis showed that the AUC was 0.790 (95%CI 0.734-0.845), and 49.5cm/s was the optimal cutoff point for the diagnosis of GD, in which the sensitivity was 64.3% and the specificity was 83.3%. In all patients with thyrotoxicosis, multiple linear regression analyses showed free thyroxine (FT(4)) (ß=0.371, 95%CI 0.005-0.010, P<0.001) and TRAb (ß=0.138, 95%CI 0.001-0.014, P=0.035) were positively associated with STA-PSV. Conclusions: The STA-PSV is positively associated with FT(4) and TRAb levels, and it is a helpful marker in differential diagnosis between GD and AIT.

[Abnormalities of white matter differentiate the Parkinson variant of multiple system atrophy from Parkinson's disease].

Objective: To identify objective markers between the Parkinson variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD). Methods: Retrospective analysis was performed on 10 patients with MSA-P, 15 patients with PD, and 15 healthy control group during the period from August 2016 to February 2019 in Baoshan Branch of Shanghai First People's Hospital.We combined the novel tract based spatial statistics (TBSS) and region of interest (ROI) analyses for the first time to investigate three groups with diffusion tensor imaging. By TBSS, we performed pairwise comparisons of mean diffusivity and fractional anisotropy (FA) maps. The clusters with significant differences between MSA-P and PD were used as ROIs for further analyses. Results: FA values in the left anterior thalamic radiation(ATR) (ROI values were 0.371(0.287-0.535), 0.472(0.390-0.594), 0.473(0.388-0.555); P values were 0.008, 0.008) and left superior longitudinal fasciculus (SLF)(ROI values were 0.397(0.291-0.469), 0.456(0.338-0.560), 0.473(0.427-0.530); P values were 0.013,<0.001) were significantly decreased in MSA-P compared with PD or controls, and significantly correlated with clinical data((r =-0.807, P =0.005),(r =-0.455, P =0.022)). Conclusion: Our findings indicate the abnormalities of left ATR and left SLF as specific biomarkers for differential diagnosis.

[Analysis of risk factors influencing the detection rate of urate crystal by dual energy computed tomography].

OBJECTIVE: To explore the risk factors of detection of uric acid crystals by dual energy CT (DECT) in patients with gout diagnosed by gold standard. METHODS: From June 2011 to December 2018, clinical data of 29 patients were collected who were diagnosed with acute or chronic gout by positive polarized light analysis of joint synovial fluid in First Hospital of Peking University. Chi-square test, Logistic regression and t-test were used. The relationship between DECT and the clinical data, laboratory examination and drug treatment were analyzed. RESULTS: In this study, 29 patients were included, of whom, 22 patients were detected with uric acid crystals by DECT, and 7 patients were not. According to whether the uric acid crystals were detected or not by DECT, the patients were divided into two groups. Compared with the negative group, the patients were older in positive group [(47±12) vs. (39±11) years, P=0.15], had higher body bass index (BMI) [(27.9±3.7) vs. (22.8±2.1) kg/m2, P=0.002], longer gout disease duration [(135±102) vs.(45±53) months, P=0.035], higher in the highest serum uric acid in history [(643±121) vs. (543±103) µmol/L, P=0.043]. Although uric acid near DECT in positive group was higher than in negative group, there was no statistical difference [(558±150) vs. (513±89) µmol/L, P=0.497]. Comparing positive group with negative group, the percentage of the patients in acute phase was higher than in chronic phase [18(81.8%) vs. 4(57%), P=0.311];the percentage of the patients taking uric-acid-lowering drugs was higher than the other group [22(100%) vs. 5 (71%), P=0.052];the percentage of the patients with recurrent typical attacks was higher than that of those without typical attacks [22 (100%) vs.6 (85%), P=0.241]. The consistency of symptoms and the finding of uric acid crystals by DECT had been compared between the joints. The right knee joint had the highest consistency (Kappa=0.627), followed by the left MTP1 (Kappa=0.58), the right metatarsophalangeal 1(MTP1, Kappa=0.551) and the left knee (Kappa=0.494), all of which had statistical significance. The consistency of the ankle joint was lower (the right ankle joint: Kappa=0.19, the left ankle joint: Kappa=0.256), showing no statistical significance. BMI (kg/m2) [2.307 (1.139-4.670), P=0.02], gout duration (years) [0.306 (0.906-4.881), P=0.186], and the highest uric acid level in history (mg/dL) [0.023 (0.981-2.764), P=0.137] had relationship to the positive result of urate crystals in DECT. CONCLUSION: Gout patients with larger BMI, higher previous highest uric acid value and longer gout duration had higher sensitivity of the positive result in DECT.