[Clinicopathological and molecular genetic features of confined placental mosaicism].

Objective: To investigate the clinicopathological and genetic features of confined placental mosaicism (CPM) and its effect on fetal intrauterine growth. Methods: Fourteen CPM cases of Haidian Maternal and Children Health Hospital were collected from May 2018 to March 2022. Clinicopathological examination on placental specimens and molecular genetic analysis were performed. Results: The age of the parturient women ranged from 27 to 34 years, with an average age of (30.0±3.54) years. The gestational weeks ranged from 35+1 to 41+2 weeks. There were 4 premature births and 10 term births, among which 6 were female and 8 were male fetuses. Nine cases (9/14) had adverse pregnancy outcomes, including 7 cases of fetal growth restriction. The weight of CPM placenta decreased, with 6 cases below the 10th percentile of weight standards and 5 cases between the 10th and 25th percentile. All 14 CPM placental specimens showed morphological changes of perfusion dysfunction to varying degrees, with mainly placental-maternal vascular malperfusion followed by placental-fetal vascular malperfusion. The mosaic chromosomes in different CPM cases varied, with 16-trisomy/monosomy mosaicism being the most common followed by 7-trisomy and 21-trisomy/monosomy mosaicism. The mosaic proportion was unequal in different parts of the same CPM placenta, with the mosaic proportion of umbilical cord, fetal membranes, fetal surface, maternal surface, and edge ranging from 1% to 70%. Conclusions: The mosaic chromosomes in different CPM cases vary, and the mosaic proportion is unequal in different parts of the same CPM placenta. The pathological morphology is mainly manifested as perfusion dysfunction, which can lead to adverse pregnancy outcomes such as fetal growth restriction and preterm birth.

[A new concept from a global perspective for expanding the treatment of chronic hepatitis B].

The global chronic hepatitis B (CHB) guidelines have gradually expanded treatment indications in order to accelerate the elimination and improve the treatment rate of hepatitis B virus (HBV) infection. This article analyzes the new treatment concepts for chronic hepatitis B at home and abroad from two aspects: expanding treatment by paying more attention to the long-term prognosis of the disease and maximizing the use of existing drugs in order to achieve the early goal of the World Health Organization's of eliminating viral hepatitis by 2030.

[Thoracoscopic laparoscopy-assisted Ivor-Lewis resection of esophagogastric junction cancer].

Objective: To investigate the outcome of patients with esophagogastric junction cancer undergoing thoracoscopic laparoscopy-assisted Ivor-Lewis resection. Methods: Eighty-four patients who were diagnosed with esophagogastric junction cancer and underwent Ivor-Lewis resection assisted by thoracoscopic laparoscopy at the National Cancer Center from October 2019 to April 2022 were collected. The neoadjuvant treatment mode, surgical safety and clinicopathological characteristics were analyzed. Results: Siewert type Ⅱ (92.8%) and adenocarcinoma (95.2%) were predominant in the cases. A total of 2 774 lymph nodes were dissected in 84 patients. The average number was 33 per case, and the median was 31. Lymph node metastasis was found in 45 patients, and the lymph node metastasis rate was 53.6% (45/84). The total number of lymph node metastasis was 294, and the degree of lymph node metastasis was 10.6%(294/2 774). Among them, abdominal lymph nodes (100%, 45/45) were more likely to metastasize than thoracic lymph nodes (13.3%, 6/45). Sixty-eight patients received neoadjuvant therapy before surgery, and nine patients achieved pathological complete remission (pCR) (13.2%, 9/68). Eighty-three patients had negative surgical margins and underwent R0 resection (98.8%, 83/84). One patient, the intraoperative frozen pathology suggested resection margin was negative, while vascular tumor thrombus was seen on the postoperative pathological margin, R1 resection was performed (1.2%, 1/84). The average operation time of the 84 patients was 234.5 (199.3, 275.0) minutes, and the intraoperative blood loss was 90 (80, 100) ml. One case of intraoperative blood transfusion, one case of postoperative transfer to ICU ward, two cases of postoperative anastomotic leakage, one case of pleural effusion requiring catheter drainage, one case of small intestinal hernia with 12mm poke hole, no postoperative intestinal obstruction, chyle leakage and other complications were observed. The number of deaths within 30 days after surgery was 0. Number of lymph nodes dissection, operation duration, and intraoperative blood loss were not related to whether neoadjuvant therapy was performed (P>0.05). Preoperative neoadjuvant chemotherapy combined with radiotherapy or immunotherapy was not related to whether postoperative pathology achieved pCR (P>0.05). Conclusion: Laparoscopic-assisted Ivor-Lewis surgery for esophagogastric junction cancer has a low incidence of intraoperative and postoperative complications, high safety, wide range of lymph node dissection, and sufficient margin length, which is worthy of clinical promotion.

[Clinical characteristics of sudden sensorineural hearing loss with acute cerebral infarction].

Objective: To analyze the clinical and imaging features of patients with sudden sensorineural deafness and acute cerebral infarction in order to provide evidence for early recognition of such diseases. Methods: This was a case series reporting study. A retrospective analysis was performed on the clinical and imaging data of 29 patients with sudden hearing loss (SHL) who admitted to the Otolaryngology Head and Neck Surgery Department of Beijing Tiantan Hospital from January 2017 to December 2021 and diagnosed with acute cerebral infarction using MRI-DWI. Results: The patients were aged 31-71 years, with an average age of 56±12 years, and 82.8% (24/29) were men. In total, 82.8% (24/29) of the patients had three or more atherosclerotic risk factors, and 24.1% (7/29) had a history of SHL. The hearing types were flat and total deafness: 86.2% (25/29) of the patients had severe hearing loss, 27.6% (8/29) had bilateral SHL, 17.2% (5/29) had further hearing loss during hospitalization, and 82.8% (24/29) had dizziness or vertigo at the onset. The signs of central nervous system involvement mainly included speech impairment, diplopia, dysphagia, central facial paralysis, facial and limb hypoesthesia, ataxia, and decreased muscle strength. Imaging evaluation showed that 21 cases were located in the posterior circulation supply area and 8 cases in the anterior circulation supply area. Additionally, 82.8% (24/29) patients had vertebrobasilar artery stenosis, and 58.6% (17/29) patients had severe vertebrobasilar artery stenosis or occlusion. Conclusions: Patients with SHL who progress to cerebral infarction often have multiple atherosclerotic risk factors and SHL. Most of the patients are middle-aged and older men who often complain of dizziness or dizziness accompanied by severe flat and total deafness with unilateral or bilateral SHL. Imaging findings suggest that most patients have posterior circulation infarction, often accompanied by severe stenosis or occlusion of the vertebrobasilar artery.

[Effect of vitamin D3 on mild cognitive impairment in type 2 diabetic mice and its possible mechanism].

OBJECTIVE: To investigate the effect of vitamin D3 on mild cognitive impairment in type 2 diabetic mice and explore its possible mechanism. METHODS: Male db/db mice were randomly divided into 4 groups: the diabetes mellitus (DM) group, the low dose [250 IU/(kg·d)], medium dose [500 IU/ (kg·d)] and high dose [1 000 IU/(kg·d)] vitamin D3 intervention groups. The db/m mice were enrolled as the normal control group. The mice in vitamin D3 groups were gavaged with corresponding concentration of vitamin D3 in corn oil, and the mice in the normal control group and the DM group were gavaged with corn oil. After being fed for 16 weeks, fasting blood glucose of mice in each group was measured at the end of 0, 4, 8 and 16 weeks, and the new object recognition experiment was conducted at the end of 16 weeks. At the end of the experiment, the hippocampi and cortices of mice in each group were collected, and the concentration of 5-hydroxytryptamine (5-HT) and interleukin-18 (IL-18) in the hippocampal tissues of mice in each group were determined by enzyme linked immunosorbent assay (ELISA). Immunohistochemical staining was used to observe the expression of nucleotide binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) in the hippocampal tissues of the mice. RESULTS: Compared with the normal control group, the fasting blood glucose of mice in DM group was significantly increased (P < 0.01). The exploration and discrimination index (DI) in the new object recognition experiment were significantly decreased (P < 0.05). The concentrations of 5-HT in the hippocampal tissues of mice were significantly decreased (P < 0.01). The concentrations of IL-18 in cortical tissues of mice were significantly increased (P < 0.01) and the positive expression of NLRP3 in the hippocampal tissues was higher. However, compared with the DM group, the fasting blood glucose of mice was significantly decreased in the medium and high dose vitamin D3 groups at the end of 8 and 16 weeks (P < 0.05 or P < 0.01). The exploration and DI of mice in the new object recognition experiment were significantly increased in high dose vitamin D3 group (P < 0.05). The concentrations of 5-HT in hippocampal tissues were significantly increased (P < 0.01) and the concentrations of IL-18 in cortical tissues were significantly decreased in the medium and high dose vitamin D3 groups (P < 0.01). The positive expression of NLRP3 in hippocampal tissues was reduced in all the vitamin D3 groups. CONCLUSION: Vitamin D3 might reduce the inflammatory response by inhibiting the activity of NLRP3, and thus ameliorating mild cognitive impairment in type 2 diabetic mice.

[Analysis of adverse neonatal outcomes in pregnant women with positive anti-Ro/SSA and anti-La/SSB antibodies].

Objective: To investigate the relationship between positive anti-Ro/Sjögren syndrome antigen type A (SSA) antibody and anti-La/Sjögren syndrome antigen type B (SSB) antibody in pregnant women and neonatal adverse outcomes. Methods: This study was a retrospective study, and 145 deliveries of 136 anti-Ro/SSA and anti-La/SSB antibody positive pregnant women were selected who had prenatal examination and delivered in Peking University First Hospital from January 2017 to June 2022. According to whether adverse neonatal outcomes occurred, 145 deliveries were divided into adverse outcome group (26 cases) and no adverse outcome group (119 cases). According to the time when anti-Ro/SSA and anti-La/SSB antibodies were found positive, 145 deliveries were divided into the antibody positive during pregnancy group (69 cases) and the pre-pregnancy antibody positive group (76 cases). The pregnancy outcomes, treatment and maternal and infant antibody levels of pregnant women between the adverse outcome group and no adverse outcome group, between antibody positive during pregnancy group and the pre-pregnancy antibody positive group were compared. Results: (1) Most of the pregnant women with positive anti-Ro/SSA and anti-La/SSB antibodies were diagnosed as undifferentiated connective tissue disease, accounting for 40.4% (55/136), followed by Sjogren's syndrome (25.0%, 34/136), systemic lupus erythematosus (23.5%, 32/136), antiphospholipid antibody syndrome (6.6%, 9/136), idiopathic thrombocytopenic purpura (1.5%, 2/136), and 4 cases were not diagnosed. (2) The titers of anti-Ro/SSA and anti-La/SSB antibodies in the first trimester and the second trimester were compared, and there were no statistical significances (all P>0.05). (3) The proportion of high level anti-Ro/SSA antibody (>100 kU/L), positive level of anti-La/SSB antibody and positive rate of anti-La/SSB antibody in the adverse outcome group were higher than those in the no adverse outcome group, and the birth weight of newborns and live birth rate in the adverse outcome group were lower than that in the no adverse outcome group, all with statistical significances (all P<0.05). The anti-Ro/SSA antibody level, the proportion of drug treatment (hydroxychloroquine, glucocorticoid, gamma globulin), the incidence of fetal growth restriction (FGR), the rate of preterm birth, and the positive level of anti-Ro/SSA and anti-La/SSB antibodies in newborns were compared between the two groups, and there were no statistically significant differences (all P>0.05). (4) The anti-Ro/SSA antibody level of pregnant women in the pre-pregnancy antibody positive group, the proportion of hydroxychloroquine and glucocorticoid treatment, and the anti-Ro/SSA antibody positive rate of newborns were higher, while the incidence of FGR and gamma globulin treatment rate of newborns in the antibody positive during pregnancy group were higher, respectively, and the differences were statistically significant (all P<0.05). The levels of anti-La/SSB antibodies in pregnant women, anti-Ro/SSA and anti-La/SSB antibodies in newborns, the positive rate of anti-La/SSB antibodies in newborns and the incidence of adverse outcomes were compared between the antibody positive during pregnancy group and the pre-pregnancy antibody positive group, and there were no statistical significances (all P>0.05). Conclusions: High concentrations of anti-Ro/SSA antibodies and co-positive anti-La/SSB antibodies during pregnancy may increase the incidence of adverse neonatal outcomes. There is no significant difference in the incidence of adverse neonatal outcomes between antibody positive pregnant women and antibody positive pregnant women who were first found during pregnancy after comprehensive treatment in the rheumatology and immunology department.

[Different treatment strategies in patients with HBeAg-positive and negative chronic hepatitis B].

Patients with HBeAg-positive and negative chronic hepatitis B (CHB) have different immunological states and disease progression. Hence, the previously recommended antiviral therapy strategies for the two are different. In recent years, the antiviral indications have gradually eased, and the treatment goal has began to pursue clinical cure, as experts and scholars have gradually attached importance to the potential risk of disease progression in hepatitis B patients. Antiviral treatment strategies are gradually becoming uniform for patients with HBeAg-positive and negative. However, among them, HBeAg-negative patients can be combined with HBsAg quantification and other indicators to further screen the clinically cured dominant population in order to formulate the next treatment strategy.

[Value of autocrine motility factors in the prediction of the disease progression of PBC- associated hepatocellular carcinoma].

Objective: To clarify the value of autocrine motility factor (ATX) in predicting the disease progression of primary biliary cholangitis (PBC)-associated hepatocellular carcinoma (HCC). Methods: A prospective cohort of 179 newly diagnosed autoimmune liver disease (PBC) patients admitted to the Department of Hepatology at the Fifth Medical Center of the People's Liberation Army General Hospital from January 2016 to January 2018 was selected. All PBC patients received ursodeoxycholic acid (UDCA) treatment and were followed up.The endpoint of the follow-up was the occurrence of primary liver cancer. The relationship between ATX and the clinical characteristics of patients and its significance in predicting disease progression and HCC were analyzed. Results: The peripheral blood ATX level was significantly higher in PBC patients than that of alcoholic cirrhosis (t = 3.278, P = 0.001) and healthy controls (t = 6.594, P < 0.001), but there was no significant difference in ATX levels compared with patients with non-PBC- associated HCC (t = -0.240, P = 0.811). The expression of ATX in liver tissue of PBC patients was significantly higher than that of healthy individuals (Z = -3.633, P < 0.001) and patients with alcoholic cirrhosis (Z = -3.283, P < 0.001), while the expression of ATX in the advanced stage was significantly higher than that in early-stage PBC patients (Z = -2.018, P = 0.034). There was a significant difference in baseline ATX levels between PBC patients without HCC and PBC patients with HCC (228.451 ± 124.093 ng/ml vs. 301.583 ± 100.512 ng/ml, t = 2.339, P = 0.021). Multivariate logistic regression analysis showed that ATX was an independent predictor of PBC progression to HCC (OR = 1.245, 95%CI 1.097-1.413). The baseline peripheral blood ATX level in predicting AUROC of PBC-associated HCC was 0.714, 95%CI 0.597-0.857 and the sensitivity and specificity were 84.6%, and 59.0%, respectively. The optimal cutoff value for predicting serum ATX levels in the occurrence of HCC was 235.254 ng/ml. Conclusion: Patients with PBC have significantly higher levels of ATX expression in their peripheral blood and liver tissue, which can be utilized to assess treatment effectiveness and predict disease progression.

[Interpretation of the essential updates in guidelines for the prevention and treatment of chronic hepatitis B (Version 2022)].

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.

[Effect of autologous hematopoietic stem cell transplantation on minimal residual disease in patients with multiple myeloma].

Objective: To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on minimal residual disease (MRD) in patients with multiple myeloma (MM). Method: From August 2018 to August 2021, 92 patients newly diagnosed with MM who had received either the bortezomib combined with cyclophosphamide and dexamethasone (VCD) or the bortezomib, lenalidomide and dexamethasone (VRD) induction regimens followed by sequential ASCT were assessed for overall survival (OS) and the MRD negative rate. The differences in efficacy at 100 days after transplantation were assessed according to factors, including age, risk stratification, target organ damage, and pre-transplant regimen, etc. Results: Among the 92 patients, there were 45 males and 47 females, with a median age of 57.3 (35-67) years. Fifty-seven patients received the VCD regimen, and 35 received VRD as induction regimen. Forty-three patients received busulphan combined with cyclophosphamide and etoposide (BCV), and 49 patients received high-dose melphan (HDM) regimen as pre-transplantation treatment. After transplantation, the total complete remission (CR) rate of 92 patients increased from 23.9% (22/92) to 58.7% (54/92), and the MRD negative rate increased from 4.4% (4/92) to 33.7% (31/92), and the differences were statistically significant (all P<0.05). After transplantation, the MRD negative rates of patients with PR, VGPR and ≥CR before transplantation were 17.6% (6/34), 33.3% (12/36) and 59.1% (13/22), respectively (P=0.006). The CR rates of patients with or without plasmacytoma at initial diagnosis were 36.4% (4/11) and 65.4% (53/81), respectively (P=0.029), and the MRD negative rates were 18.2% (2/11) and 39.5% (32/81), respectively (P=0.037), and the differences were statistically significant. The MRD negative rates in high-risk patients and standard-risk group were 30.5% (12/28) and 42.9% (18/59), respectively (P=0.258). For patients who achieved efficacy above VGPR before transplantation, the MRD negative rates after transplantation in VCD-induced group and VRD group were 29% (9/31) and 59.3% (16/27), respectively (P=0.033), and in BCV group and HDM group were 24% (6/25) and 57.6% (19/33), respectively (P=0.016), the differences between the groups were both statistically significant. Conclusion: ASCT can overcome the adverse factors such as high-risk cytogenetic abnormalities, and significantly improve the CR rate and MRD negative rate of MM patients. However, the benefit for patients with plasmacytoma at initial diagnosis is not as good as that of patients without.

[Expanding antiviral therapy for chronic hepatitis B: scale up screening and treatment].

The Chinese Society of Hepatology, Chinese Medical Association published "Expert Opinions on Expanding Antiviral Therapy for Chronic Hepatitis B" in 2022, with a focus on "active screening of the existing patients, paying attention to the potential risk of disease progression, and active intervening of the low level viremia," and recommended that specific actions be taken to further optimize the expanding screening, widening the antiviral indications, and scale up the diagnosis and treatment of low level viremia.

[Diagnostic efficiency and incremental value of myocardial blood flow quantification by CZT SPECT for patients with coronary artery disease].

Objective: To investigate the diagnostic efficiency and incremental value of quantitative myocardial blood flow measurements by Cadmium-Zine-Telluride (CZT) single photon emission computed tomography (SPECT) dynamic myocardial perfusion imaging (MPI) in patients with coronary artery disease (CAD) compared with traditional semi-quantitative measurements by MPI. Methods: This is a retrospective, cross-sectional study. We retrospectively analyzed clinical data of patients with suspected or known CAD, who underwent the dynamic MPI quantitative blood flow measurement of CZT SPECT in TEDA International Cardiovascular Hospital from October 2018 to December 2020. Clinical data, semi-quantitative parameters (stress score (SS), rest score (RS) and different score (DS)) and myocardial quantitative blood flow parameters (rest myocardial blood flow (rMBF), stress myocardial blood flow (sMBF) and myocardial flow reserve (MFR)) were analyzed. According to the results of coronary angiography, patients were divided into the stenosis group and the control group with coronary artery stenosis ≥50% or ≥75% as the diagnosis criteria. The differences of quantitative and semi-quantitative parameters between the two groups were compared, and the diagnostic efficacy was compared by receiver operating characteristic(ROC) curve. Results: A total of 98 patients with a mean age of (62.1±8.7) years were included in the study, including 66 males (67%). At the patient level, with the positive standard of coronary artery stenosis≥50%, the left ventricle (LV) stress MBF (LV-sMBF) ((1.36±0.45) ml·min-1·g-1) and LV-MFR (1.45±0.43) of the stenosis group were lower than the LV-sMBF ((2.09±0.64) ml·min-1·g-1) and LV-MFR (2.17±0.54) of control group; summed SS and summed DS were higher than control group (all P<0.05). With the positive standard of coronary artery stenosis ≥75%, the LV-sMBF ((1.19±0.34) ml·min-1·g-1) and LV-MFR (1.34±0.35) of stenosis group were lower than the LV-sMBF ((1.94±0.63) ml·min-1·g-1) and MFR (2.00±0.58) of control group; all semi-quantitative parameters were higher than control group (all P<0.05). At the vascular level, with coronary artery stenosis ≥50% as the diagnosis criteria, the sMBF ((1.26±0.49) ml·min-1·g-1) and MFR (1.35±0.46) of stenosis group were lower than the sMBF ((1.95±0.70) ml·min-1·g-1) and MFR (2.05±0.65) of control group; SS and DS were higher than control group (all P<0.05). With coronary artery stenosis≥75% as the diagnosis criteria, the sMBF ((1.12±0.41) ml·min-1·g-1) and MFR (1.25±0.38) of stenosis group were lower than the sMBF ((1.84±0.70) ml·min-1·g-1) and MFR (1.93±0.66) of control group; all semi-quantitative parameters were higher than control group (all P<0.05). With coronary artery stenosis≥50% as the diagnosis criteria and CAG as the reference standard, the AUC and 95%CI of myocardial quantitative blood flow parameters indicated by ROC curve for diagnosis of CAD were 0.830 (0.783-0.877). The sensitivity (86.1% vs. 61.5%), specificity (82.6% vs. 73.8%), positive predictive value (77.8% vs. 62.5%), negative predictive value (89.3% vs. 73.0%) and accuracy (84.0% vs. 68.7%) were all higher than the semi-quantitative parameters (all P<0.05). With coronary artery stenosis≥75% as the diagnosis criteria, the AUC and 95%CI of myocardial quantitative blood flow parameters indicated by ROC curve for diagnosis of CAD were 0.832(0.785-0.879). The sensitivity (89.2% vs. 67.6%), negative predictive value (95.5% vs. 86.2%) and accuracy (80.6% vs. 68.0%) were all higher than semi-quantitative parameters (all P<0.05). Conclusion: Compared with traditional SPECT MPI derived semi-quantitative parameters, diagnostic efficacy for CAD is higher using CZT SPECT quantitative myocardial blood flow parameters, this strategy thus has additional diagnostic benefits and incremental value on the diagnosis of CAD.

[The possibility of neoadjuvant chemotherapy course adjustment for delayed operation of patients with esophageal cancer in special period].

Objective: To investigate the effect of the neoadjuvant chemotherapy course adjustment on the patients with esophageal cancer underwent delayed operation. Methods: The clinical data of patients with esophageal cancer treated in Cancer Hospital, Chinese Academy of Medical Sciences from 2019-2020, who underwent neoadjuvant chemotherapy strategy adjustment (multiple course chemotherapy group) or not (control group), were retrospectively studied. The clinical pathological characteristics and postoperative complication of these two group were compared and analyzed. Results: The cases who underwent the interval between chemotherapy and operation more than 4 weeks in multiple course chemotherapy group and control group were 17 and 6, with significant difference (P<0.05). The average operative blood loss of these two groups were 88.6 ml and 46.1 ml, the average postoperative hospital stays were 14.7 days and 10.0 days, with significant difference (P<0.05). The incidence rate of postoperative complication in the multiple course chemotherapy group was 40.9% (9/22), not significantly different from 31.8% (7/22) of control group (P>0.05). There were no death within postoperative 7 days and 30 days in both groups. Cases with apparent tumor regression [tumor regression grade (TRG) 1 to 3] in multiple course chemotherapy group were 14, with marginal tumor regression (TRG 4 to 5) were 8, while there were 7 and 15 in the control group, respectively, with significant difference (P<0.05). After multiple neoadjuvant chemotherapy, the imaging examination of patients indicated an almost total tumor degradation and the postoperative pathology showed no residual malignant tumor tissue was observed. Conclusions: Increased neoadjuvant chemotherapy course for patients with locally advanced esophageal cancer can obtain more obvious tumor degradation response. Neoadjuvant chemotherapy adjustment according to the operation schedule is recommended.

[Exploring and bioinformatics analysis of differentially expressed genes in bronchial asthma].

Objective: To screen core differentially expressed genes of bronchial asthma and conduct bioinformatics analysis. Methods: Macrophage microarray data GSE22528 from asthma patients were downloaded from gene expression database (GEO). The dataset included transcriptome information from 10 human alveolar lavage fluid samples, and five of them were from allergic asthmatic subjects and five from control subjects. Differential expression genes (DEGs) were screened by R 4.0.4 software. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to select DEGs using DAVID 6.8 database. Protein interaction network (PPI) was constructed from DEGs encoded proteins using STRING online database. Cytoscape software was used to construct core modules and determine core DEGs. Results: Alveolar lavage fluid samples were all collected from Caucasian Canadians, with age range as (20, 37) and (18, 36) years, respectively, including 3 males for each group. In asthmatic patients, 449 genes were up-regulated and 47 down-regulated. GO analysis showed that the up-regulated genes in asthmatic patients were mainly involved in biological processes such as response to folded proteins, and the molecular function was focused on binding of folded proteins and growth factors. Down-regulated genes were mainly involved in biological processes such as histone deacetylation and ubiquitin-mediated protein degradation, and their molecular functions focused on histone deacetylation activity. KEGG pathway enrichment analysis showed that pathways were mainly enriched by up-regulation genes, involving Hippo signaling pathway, hypertrophic cardiomyopathy, estrogen signaling pathway, arrhythmogenic right ventricular cardiomyopathy, basal cell carcinoma, neuro-activated receptor ligand interaction, dilated cardiomyopathy and adhesion and connection signaling pathways. Two core modules were obtained by PPI analysis, and 14 core DEGs were screened out. They were pro-melanin concentrating hormone (PMCH), prepronociceptin (PNOC), Sphingosinol-1-phosphate receptor 2 (S1PR2), Sphingosinol-1-phosphate receptor 5 (S1PR5), CC-type chemokine ligand 21 (CCL21), Kelch-like protein 25 (KLHL25), ubiquitin binding enzyme E2V2 (UBE2V2), F-box protein 17 (FBXO17), taste receptor type 2 member 3 (TAS2R3), somatostatin receptor 2 (SSTR2), metabolic glutamate receptor 2 (GRM2), Lister E3 ubiquitin protein ligase 1 (LTN1), LIM domain specific protein 7 (LMO7) and ring finger protein 19A gene(RNF19A), in which LTN1 and UBE2V2 were down-regulated and the rest were up-regulated. Conclusion: DEGs was found in macrophages of asthmatic and control individuals. PMCH, PNOC, S1PR2, S1PR5 and CCL21 might be the core genes in the pathological process of asthma.

[The diagnostic performance of 2020 Chinese Ultrasound Thyroid Imaging Reporting and Data System in thyroid nodules].

Objective: To evaluate the diagnostic performance of the Chinese Ultrasound Thyroid Imaging Reporting and Data System (C-TIRADS) in thyroid nodules,and to compare it with the TIRADS proposed by Kwak et al. (K-TIRADS) and the TIRADS proposed by the American College of Radiology (ACR-TIRADS). Methods: The data of 1 750 patients with 2 029 thyroid nodules in the Department of Thyroid Surgery, the Affiliated Hospital of Jining Medical University from January 2018 to November 2020 was retrospectively collected. Among them, there were 328 males and 1 422 females,aged from 6 to 86 with an average of (47±12) years. The nodules were divided into≤1.0 cm group(n=997) and>1.0 cm group(n=1 032)based on the size of the nodules. The stratification for malignant risk and the determination of benign or malignancy of the nodules was evaluated using the C-TIRADS, K-TIRADS and ACR-TIRADS, respectively. The receiver operating characteristic (ROC)curve analysis was performed to compare the diagnostic performance of the aforementioned three kinds of TIRADS using pathological results as the referent standard. Results: The optimal diagnosis points in the determination of malignant nodules of C-TIRADS, K-TIRADS and ACR-TIRADS in the two groups were 4A, 4b and 4 respectively according to ROC curve analysis. For the diagnosis of the malignant nodules, the C-TIRADS achieved with an AUC value of 0.772 and 0.892 in the ≤1.0 cm group and>1.0 cm group, respectively, which was significantly higher than K-TIRADS (AUC= 0.762 and 0.869, respectively) and ACR-TIRADS (AUC= 0.735 and 0.832, respectively) (P<0.05). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of C-TIRADS were 94.99%, 59.41%, 86.46%, 88.13%, 78.89% (≤1.0 cm group)and 88.34%, 90.05%, 89.34%, 86.33%, 91.57%(>1.0 cm group), respectively. C-TIRADS had the highest sensitivity, accuracy, and negative predictive value in the determination of malignant nodules in both groups compared to the other two kinds of TIRADS. Conclusions: The three kinds of TIRADS all have high diagnostic performance for the determination of the malignant nodules, and the C-TIRADS has the best overall efficacy, which can effectively assist clinicians for medical decision, and is worth to be popularized and applied in the clinical setting.

[A cohort study on plasma uric acid levels and the risk of type 2 diabetes mellitus among the oldest old in longevity areas of China].

Objective: To investigate the effect of plasma uric acid level on the incident risk of type 2 diabetes mellitus (T2DM) among the oldest old (those aged ≥80 years). Methods: Participants were recruited from the Healthy Aging and Biomarkers Cohort Study (HABCS), which conducted a baseline survey in 2008-2009 and follow-up of 3 times in 2011-2012, 2014, and 2017-2018, respectively. A total of 2 213 oldest old were enrolled in this study. The general demographic, socioeconomic, lifestyle and disease data of the oldest old were collected, and physical measurements were made for the oldest old. Fasting venous blood was collected for uric acid and blood glucose detection. Information on the incident and death of T2DM were collected through the follow-up. Cox proportional hazard regression model was used to explore the association of hyperuricemia and plasma uric acid level with the incidence of T2DM. Restricted cubic spline (RCS) function was used to explore the dose-response relationship of plasma uric acid levels with the risk of T2DM. Results: The age of participants was (93.2±7.6) years old, and 66.7% of the participants (1 475) were female. The plasma uric acid level at baseline was (289.1±88.0)µmol/L, and the prevalence of hyperuricemia was 13.3% (294 cases). During 9 years of cumulative follow-up of 7 471 person-years (average of 3.38 years for each), 122 new cases of T2DM occurred and the incidence density was 1 632.98/105 person year. Cox proportional hazards regression analysis showed that per 10µmol/L increase in plasma uric acid level, the risk of T2DM increased by 1.1% [HR (95%CI): 1.011 (1.004, 1.017)]. Compared with the participants with the lowest quintile of plasma uric acid (Q1), the risk of diabetes increased by 20.7 % among the oldest old with uric acid in the highest quintile (Q5) [HR (95%CI):1.207 (1.029, 1.416)]. The risk of T2DM was 19.2% higher in the hyperuricemia group than that in the oldest old with normal plasma uric acid [HR (95%CI): 1.192 (1.033, 1.377)]. RCS function showed that the risk of T2DM increased with the increase in plasma uric acid levels in a nonlinear dose-response relationship (P=0.016). Conclusion: The incident risk of T2DM increases with the elevates of plasma uric acid levels in the oldest old.

[Association of blood oxidative stress level with hypertriglyceridemia in the elderly aged 65 years and older in 9 longevity areas of China].

Objective: To investigate the association of blood oxidative stress level with hypertriglyceridemia in the elderly aged 65 years and older in China. Methods: A total of 2 393 participants aged 65 years and older were recruited in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study, during 2017 to 2018. Information on demographics characteristic, life style and health status were collected by questionnaire and physical examination, and venous blood was collected to detect the levels of blood oxidative stress and hypertriglyceridemia. The linear or non-linear association between oxidative stress and hypertriglyceridemia was described by restrictive cubic splines (RCS) fitting multiple linear regression model. The generalized linear mixed effect model was conducted to assess the association between oxidative stress and hypertriglyceridemia. Results: A total of 2 393 participants, mean age was 84.6 years, the youngest was 65 and the oldest was 112, the male was 47.9%(1 145/2 393), the triglyceride level was (1.4±0.8) mmol/L. The hypertriglyceridemia detection rate was 9.99%(239/2 393). The results of multiple linear regression model with restrictive cubic spline fitting showed that MDA level was linear association with triglyceride level; SOD level was nonlinear association with triglyceride level. MDA level had significantly association with hypertriglyceridemia, and the corresponding OR value was 1.063 (95%CI: 1.046,1.081) with 1 nmol/ml increment of blood MDA; SOD level had significantly association with hypertriglyceridemia, and the corresponding OR value was 0.986(95%CI: 0.983,0.989) with 1 U/ml increment of blood SOD. Conclusion: Among the elderly aged 65 and older in 9 longevity areas in China, MDA and SOD levels were associated with the risk of hypertriglyceridemia.

[Association of blood lead level with cognition impairment among elderly aged 65 years and older in 9 longevity areas of China].

Objective: To investigate the association between blood lead concentrations and cognition impairment among Chinese older adults aged 65 or over. Method: Data was collected in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study between 2017 and 2018. This study included 1 684 elderly aged 65 years and older. Information about demographic characteristics, socioeconomic factors, health status and cognitive function score of respondents were collected by questionnaire survey and physical examination. Venous blood of the subjects was collected to detect the blood lead concentration. Subjects were stratified into four groups (Q1-Q4) by quartile of blood lead concentration. Multivariate logistic regression model was used to analyze the association between blood lead concentration and cognitive impairment. The linear or non-linear association between blood lead concentration and cognitive impairment were described by restrictive cubic splines (RCS). Results: Among the 1 684 respondents, 843 (50.1%) were female and 191 (11.3%) suffered from cognition impairment. After adjusting for confounding factors, the OR value and 95%CI of cognition impairment was 1.05 (1.01-1.10) for every 10 µg/L increase in blood lead concentration in elderly; Compared with the elderly in Q1, the elderly with higher blood lead concentration had an increased risk of cognitive impairment. The OR value and 95%CI of Q2, Q3 and Q4 groups were 1.19 (0.69-2.05), 1.45 (0.84-2.51) and 1.92 (1.13-3.27), respectively. Conclusion: Higher blood lead concentration is associated with cognitive impairment among the elderly aged 65 years and older in 9 longevity areas in China.

[Immune pathogenesis of primary biliary cholangitis].

Primary biliary cholangitis (PBC) is an autoimmune liver disease, mainly characterized by chronic progressive cholestasis. The root cause of PBC is the loss of immune tolerance to autoantigen E2 subunit of pyruvate dehydrogenase (PDC-E2). The unique immunobiological characteristics of intrahepatic bile duct epithelial cells make it an active participant in the pathogenesis of PBC. In recent years, the detection rate of PBC has been increasing year by year, but the clinical situation of ursodeoxycholic acid monotherapy has not changed. Therefore, an in-depth understanding of the immune pathogenesis of PBC will help clinicians better prevent and treat diseases.

[Human bone marrow mesenchymal stem cells improve steroid resistance of human airway epithelial BEAS-2B cells in vitro].

Objective: To explore the effect of human bone marrow mesenchymal stem cells(MSC) on the steroid resistance of human airway epithelial cells. Methods: Ovalbumin (OVA)/lipopolysaccharide (LPS) were used to construct steroid resistant BEAS-2B cells, which were then co-cultured with MSC. Groups were set as follows: blank group, model group, Glucocorticoid group, MSC group, MSC+Glucocorticoid group (MSC+bud group). The expression of interleukin (IL)-8 in the cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA); the expression of reactive oxygen species (ROS) in the cells was detected by flow cytometry; the expression of glucocorticoid receptor α (GRα) and histone deacetylase 2 (HDAC2) protein in the cell was detected by Western blotting; and the expression of GRα and HDAC2 mRNA was detected by reverse transcription-polymerase chain reaction (RTPCR). Results: The expression level of IL-8 in the MSC group was significantly lower than that in the Glucocorticoid group (31.7±0.7 vs. 49.8±3.6, P<0.01). The expression of ROS in the MSC group was significantly lower than that in the Glucocorticoid group (2754±154 vs.4624±228, P<0.05). The expression level of HDAC2 mRNA in the MSC group was significantly higher than that in the Glucocorticoid group(1.749±0.005 vs. 1.283±0.098, P<0.05). The expression level of GRα mRNA in the MSC group was significantly higher than that in the Glucocorticoid group (1.623±0.079 vs.1.047±0.220, P<0.01). The expression of HDAC2 protein in the MSC group was significantly higher than that in the Glucocorticoid group (1.067±0.100 vs. 0.620±0.083, P<0.01). The expression of GRα protein in the MSC group was significantly higher than that in the Glucocorticoid group (0.834±0.053 vs. 0.579±0.017, P<0.01). ROS was positively correlated with the IL-8 expression (r=0.796, P<0.01) and negatively correlated with the HDAC2 and GRα mRNA expression (r=-0.893 3, P<0.01; r=0.931 4, P<0.01, respectively), as well as the HDAC2 and GRα Protein expression (r=-0.929 5, P<0.01;r=-0.864 3, P<0.01, respectively). Conclusions: Human MSC can improve steroid resistance of airway epithelial cells in an exocrine manner. The mechanism may be related to the down-regulation of ROS and up-regulation of HDAC2, which lead to GRα overexpression. In addition, MSC may improve the steroid resistance by reducing the expression of IL-8.