[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Risk perception for fractures and its related factors among family caregivers of underage patients with osteogenesis imperfecta in China: A cross-sectional study.

PURPOSE: To describe the level of risk perception for fractures among family caregivers of children diagnosed with osteogenesis imperfecta, and explore the related factors. DESIGN AND METHODS: This was a cross-sectional survey study. A self-administered questionnaire on family caregivers' perception of fracture risk of underage patients with osteogenesis imperfecta was used. The study was performed in mainland China from May to December 2022, with 127 family caregivers of patients aged 3-17. Stepwise backwards multivariable linear regression analysis was undertaken to examine risk factors for caregivers' risk perception of fractures. RESULTS: A total of 16.54% of caregivers had a higher level of risk perception for fractures of patients. The caregiver's educational level, the family members, the patient's self-care ability, fracture times in the past year, and whether or not they had received community services were associated with the caregiver's risk perception for fracture. CONCLUSIONS: Patients with osteogenesis imperfecta will eventually leave the medical system and receive more support from themselves or family caregivers instead of health personnel. These findings should be incorporated into the prevention and health education of fractures in caregivers of underage patients with osteogenesis imperfecta to help develop effective risk communication strategies and induce caregivers to implement appropriate protective behaviors. PRACTICE IMPLICATIONS: It is important to evaluate the risk perception for fractures and its related factors among family caregivers of underage patients with osteogenesis imperfecta. Identifying these factors can help healthcare providers to screen caregivers with high perceived level of fracture risk in a quicker and earlier way. This study provides evidence for the establishment of interventions to balance caregivers' risk perception and patient socialization.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[Treatment of intrauterine adhesions in rats with hypoxia-cultured BMSC-derived exosomes].

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O2) or hypoxia condition (1%O2). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×106/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×106/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 µg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 µg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD31], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor ß1 (TGF-ß1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-ß1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-ß1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-ß1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-ß1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD31 showed that, the expressions of VEGFA and CD31 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD31 in BMSC-exo group and CD31 in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD31 in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.

Association of non-alcoholic fatty liver disease with total testosterone in non-overweight/obese men with type 2 diabetes mellitus.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is considered as both a vital risk factor and a consequence of type 2 diabetes mellitus (T2DM). Low total testosterone (TT) is common in men with T2DM, contributing to increased risks of metabolic diseases. This study aimed to investigate the association between TT levels and the prevalence of NAFLD in men with T2DM. METHODS: In this cross-sectional study, 1005 men with T2DM were enrolled in National Metabolic Management Center (MMC) of First Affiliated Hospital of Wenzhou Medical University between January 2017 and August 2021. NAFLD was diagnosed using ultrasound as described by the Chinese Liver Disease Association. Overweight/obesity was defined as body mass index (BMI) ≥ 25 kg/m2 according to WHO BMI classifications. RESULTS: Individuals without NAFLD had higher serum TT levels than those with NAFLD. After adjustments for potential confounding factors, the top tertile was significantly associated with lower prevalence of NAFLD compared with the bottom tertile of TT level [odds ratio (OR) 0.303, 95% confidence interval (CI) 0.281-0.713; P < 0.001]. The association between TT with NAFLD in individuals with normal weight (OR 0.175, 95% CI 0.098-0.315; P < 0.001) was stronger than in individuals with overweight/obesity (OR 0.509, 95% CI 0.267-0.971; P = 0.040). There was a significant interaction of TT with overweight/obesity (P for interaction = 0.018 for NAFLD). CONCLUSION: Higher serum TT was significantly associated with a lower prevalence of NAFLD in men with T2DM. We found that the relationship of TT and NAFLD was stronger in individuals with non-overweight/obesity.

[Survival and prognosis analysis of patients with Hodgkin lymphoma treated with standard treatment paradigm].

Objective: To analyze the survival and prognosis of Hodgkin lymphoma (HL) patients receiving standard first-line therapy. Methods: Data of clinical characteristics and treatment outcomes of patients with HL diagnosed in Cancer Hospital Chinese Academy of Medical Sciences (CHCAMS) from January 1st, 2000 to December 31st, 2018 who received standard first-line treatment were retrospectively analyzed and compared with that of HL patients who received treatment in the Surveillance, Epidemiology and End Results (SEER) database in the United States during the same period. Factors associated with freedom from progression (FFP) of patients in CHCAMS were analyzed. Treatment and survival data of patients with relapsed/refractory HL (r/rHL) who had failed the standard first-line treatment during the corresponding period in CHCAMS were collected to analyze the outcomes of salvage therapy. Results: A total of 764 HL patients in CHCAMS were included in this study. The median age was 30 years (range, 14-83 years), with 424 males and 340 females. By February 26th, 2022, the patients were followed-up for a median time of 111 months(range, 0.3-262.0 months). Lymphoma-specific survival (LSS) rate and overall survival (OS) rate at 10 years for HL patients in CHCAMS was 91.7% (95%CI: 89.5%-93.9%) and 87.1% (95%CI: 84.5%-89.8%), respectively. LSS and OS rate at 10 years for HL patients from SEER database was 86.8% (95%CI: 86.3%-87.2%) and 79.0% (95%CI: 78.5%-79.5%), respectively. The unadjusted LSS and OS rate for patients in CHCAMS were higher than those for patients from SEER database (both P<0.001). No significant difference was observed in LSS and OS rate (both P>0.05) between the two groups after adjustment. European Organization for Research and Treatment of Cancer staging system (early-stage unfavorable: HR=2.35, 95%CI: 1.13-4.89, P=0.023; advanced stage: HR=5.44, 95%CI: 2.62-11.30, P<0.001) and serum ß2 microglobulin (HR=1.67, 95%CI: 1.08-2.58, P=0.021) were influencing factors of FFP for patients in CHCAMS. The complete remission rate, median progression-free survival (PFS), 5-year PFS rate and 5-year OS rate for the 116 patients with r/rHL was 37.9% (95%CI: 29.6%-47.0%), 15.0 months (95%CI: 9.9-20.1 months), 29.9% (95%CI: 20.9%-38.9%) and 62.9% (95%CI: 54.1%-71.7%), respectively. Conclusions: The outcomes of HL patients receiving standard first-line treatment are excellent. However, the therapeutic effect of HL patients who incurrs disease progression or relapse after standard first-line treatment is not satisfying.

A clinical investigation into the usefulness of fractional exhaled nitric oxide in guiding glucocorticoid therapy in children with bronchial asthma.

The present study aims to investigate the value of fractional exhaled nitric oxide (FeNO) combined with pulmonary function in guiding the dose adjustment of inhaled glucocorticosteroids (ICSs) in children with asthma. A total of 133 children aged 6-12 years with newly diagnosed asthma were enrolled as the study subjects and randomly divided into the experimental group (n=68) and the control group (n=65). After three months of ICS treatment, in the experimental group, the dose of ICSs was adjusted based on the control status of the children and the results of the pulmonary function tests and FeNO assays, and in the control group, the dose was adjusted based on the control status of the children and the results of the pulmonary function tests. After another three months of treatment, the number of acute asthma attacks and the Childhood Asthma Control Test (C-ACT) scores were compared between the two groups, and the outcome of pulmonary function tests and FeNO assays during treatment were analyzed. When examining pulmonary function and FeNO levels, when compared with before treatment, there were no statistically significant differences in either group or between the groups after three months of ICS treatment (P>0.05). After dose adjustment and another three months of treatment, when compared with the control group, the improvement in pulmonary function in the experimental group was greater, the reduction in FeNO levels was greater, the incidence of acute asthma attacks was lower, and the C-ACT score was higher (P<0.05). We concluded that the combination of FeNO assays and pulmonary function tests to guide the ICS dose adjustment in children with asthma could improve asthma control and reduce the risk of acute asthma attacks.

[Efficacy of early interdisciplinary palliative care based on WARM model in non-small-cell lung cancer].

Objective: To assess the therapeutic effect of the early interdisciplinary palliative care based on WARM model (whole, assessment, revaluation, management) on the quality of life, psychological state, pain and nutritional status in patients with non-small-cell lung cancer (NSCLC). Methods: A total of 60 patients from Chongqing University Cancer Hospital with newly diagnosed advanced NSCLC from Oct 15, 2019 to Jun 12, 2020 were enrolled. According to the method of random number table, the patients were divided into two groups: standard oncologic care group (SC, n=30) and early palliative care group (EPC, n=30). SC group only received standard oncological care, while EPC group received standard oncological care and additional comprehensive treatment from a MDT consisted of medical oncologists, palliative care nurses, dietitians and psychologists. The quality of life [functional assessment of cancer therapy-lung (FACT-L) scale], psychological state [hospital anxiety and depression scale (HADS) and patient health questionnaire-9 (PHQ-9)], nutritional status [patient-generated subjective global assessment (PG-SGA)], and cancer pain status [numerical rating scale (NRS)] were observed and compared between the two groups before and after the 6 months treatment, respectively. Results: A total of 45 patients completed 6 months treatment, including 24 males and 21 females, aged 38-82 (60.5±1.7), with 23 patients in the EPC group and 22 patients in the SC group. Patients assigned to EPC group had a better quality of life than those assigned to SC group [FACT-L scale: (122.3±1.6) vs (111.8±2.1), P<0.001]. Fewer patients had anxiety and depressive symptoms in the EPC group than those in the SC group [HADS anxiety subscale: (1.1±0.3) vs (2.9±0.4), P<0.001; HADS depression subscale: (0.7±0.3) vs (3.6±0.4), P<0.001]. The PHQ-9 results showed that 100.0% (23/23) patients were free of depression in the EPC group, while 45.5% (10/22) patients were free of depression in SC group (P<0.001). Furthermore, patients in the EPC group had a better nutritional status [moderate malnutrition: 60.9% (14/23); no malnutrition: 39.1% (9/23)] than those in the SC group [severe malnutrition: 40.9% (9/22); moderate malnutrition: 50.0% (11/22); no malnutrition: 9.1% (2/22)] (P<0.001). There was no significant difference in NRS score between EPC group and SC group (P=0.140). Conclusion: Early interdisciplinary palliative care based on WARM model can improve the quality of life, psychological state and nutritional status in NSCLC patients.

[Surgical diagnosis and treatment of adult huge undifferentiated embryonal sarcoma of the liver].

Objective: To investigate the clinical characteristics of adult undifferentiated embryonal sarcoma of the liver (UESL). Methods: A retrospective analysis was performed on the clinical data of 5 patients with UESL who underwent surgical resection and were pathologically confirmed from January 2005 to December 2020 at the First and the Second Affiliated Hospital of Anhui Medical University. All the patients were female aged from 49 to 77 years old. Preoperative CT showed a solid cystic mass with low density and a slight density of cord like septum. Imaging findings were misdiagnosed as hepatocellular carcinoma or cystadenocarcinoma. CA125 was higher in 3 patients,and AFP in all patients was normal. Results: All patients were treated by surgery. The mean diameter of tumor was 20.2 cm (range:15.0 to 30.0 cm). All five patients had vimentin expression in immunohistochemistry. Three cases underwent complete resection of the tumor and achieved R0 resection,2 of them had tumor free survival until the end of the follow-up (89 and 55 months),the other 1 case died from renal cell carcinoma 158 months later. The remaining 2 cases were radically resected,but the tumors were ruptured during operation,and relapsed after 2 months and 19 months respectively. The overall survival was 3 and 26 months respectively. Conclusions: Radical hepatectomy is the first choice for treatment of UESL. Intraoperative tumor rupture should be avoided and implant metastasis is a major factor affecting the prognosis of UESL.

[Expression of peroxisome proliferator-activated receptor-gamma coactivator 1ß in synovium in patients with rheumatoid arthritis and its clinical significance].

Objective: To investigate the expression of peroxisome proliferator-activated receptor-gamma coactivator (PGC)1ß in synovium of patients with rheumatoid arthritis (RA) and its association with histological synovitis. Methods: This cross-sectional study recruited RA patients at the Department of Rheumatology, Sun Yat-Sen Memorial Hospital from May 2010 to October 2016. Clinical data were collected. Conventional radiographs of bilateral hands and wrists were performed and assessed according to Sharp/van der Heijde-modified Sharp score(mTSS). Synovial tissues from knee joints of all RA patients were obtained by biopsies, and then stained with HE and immunohistochemically for PGC-1ß, CD3, CD20, CD38, CD68, CD15 and CD34 to evaluate synovitis, synovial PGC-1ß expression and the densities of inflammatory cells and endothelial cells. The relationship between synovial PGC-1ß expression and histological synovitis, disease activity and joint destruction in RA was analyzed by Spearman's rank correlation and multivariate linear regression. Results: There were 83 RA patients recruited with 20 (24.1%) males and 63 (75.9%) females, aged (54±14) years. PGC-1ß expressed in the nuclei of lining synoviocytes, sublining inflammatory cells and vascular endothelial cells of RA synovium. The percentage of synovial PGC-1ß+cells was positively correlated with histological synovitis score (r=0.333) and the densities of sublining CD3+ T cells (r=0.259), CD20+ B cells (r=0.320), CD38+plasma cells (r=0.342) and CD68+ macrophages (r=0.309)(all P<0.05). It was also positively correlated with erythrocyte sedimentation rate, C reactive protein and total mTSS (r=0.219-0.301, all P<0.05). Multiple linear regression analysis further confirmed the positive correlation between the percentage of synovial PGC-1ß+cells and mTSS (ß=0.312, P=0.004). Conclusion: Synovial PGC-1ß is positively associated with local and systemic inflammation as well as joint destruction, which implies that PGC-1ß might involve in the pathogenesis of synovitis and joint destruction in RA.

Whole-genome resequencing reveals genetic structure and introgression in Pudong White pigs.

Pudong White (PDW) pigs, historically originating from Shanghai, are the only Chinese indigenous pigs characterised by their completely white coats, with the exception of Rongchang pigs. However, there is limited information concerning their overall genetic structure or relationship with other breeds, especially the East Chinese (ECN) and European pigs. To uncover the genetic structure, selection signatures, and potential exotic introgression in PDW pigs, we sampled 15 PDW pigs using whole-genome sequencing (~20×). We then conducted in-depth population genetic analyses in 320 pigs from 27 global pig groups, namely, European wild boars, Chinese wild boars, and outgroup. Neighbour-joining tree and principal component analysis confirmed that PDW pigs belonged to the ecotype of ECN pigs. Both f3, D-statistics, and structure analysis showed that PDW pigs shared apparent alleles with Large White (LW) pigs. Three statistics, rIBD, a haplotype heat map and copy number variation, further indicated that PDW pigs shared apparent alleles with LW pigs at the KIT Proto-Oncogene, Receptor Tyrosine Kinase (KIT) and PARG-MARCHF8 loci, suggesting that the lineage of European pigs in PDW originated from LW pigs. After further detecting the KIT mutations in different pig breeds, PDW was confirmed to have the same duplication region 1, duplication region 2, and the splicing mutation on intron 17 of KIT as LW pigs that determine the white coat colour phenotype in European white pigs. We hypothesised that LW pigs were imported to China ∼110-160 years ago according to the admixture time estimate and then crossed with ECN pigs, resulting in the introgression of the KIT alleles that produce the white coat colour phenotype in the PDW pig breed. To our knowledge, this study presents the first thorough description of the genetic structure of PDW pigs via whole-genome resequencing data; moreover, the results provide a basis for the national project for the conservation of this unique Chinese local population.

Olig2 knockdown alleviates hypoxic-ischemic brain damage in newborn rats.

OBJECTIVES: Neuronal damage is an important pathological mechanism in neonatal hypoxic-ischemic brain damage (HIBD). We found in our previous studies that oligodendrocyte transcription factor 2 (Olig2) downregulation was able to increase cell survival in the brain. However, the specific mechanism has yet to be clarified. METHODS: Sprague-Dawley rats aged 3 d were randomly divided into three groups: the normal control group, the Olig2-RNAi group, and the RNAi-negative control group. The normal control group received no treatment, the Olig2-RNAi group received the Olig2 RNAi adenovirus, and the RNAi-negative control group was given the control adenovirus after the completion of the HIBD model. Infarct lesions and their volumes were observed by triphenyltetrazolium chloride (TTC) staining 3 d after the completion of the adenovirus local injection. The condition of the tissue was characterized by hematoxylin-eosin staining 7 d after the model was established, and cell viability was determined by azure methylene blue staining. Subcellular damage was analyzed by transmission electron microscopy. Rotarod analysis was performed to detect moving behavior ability and an MWM assay was conducted to evaluate the memory. RESULTS: TTC staining showed a smaller brain injury area in the Olig2-RNAi group than in the RNAi-negative control group. Hematoxylin-eosin staining indicated the presence of severe cell injury in the hippocampal region after HIBD, which improved after Olig2 knockdown. Azure methylene blue staining and electron microscopy results suggested that the cells improved after Olig2 knockdown. The rats stayed longer on the rotating rod, and their latency in the water maze test was gradually shortened relative to that of the rats in the Olig2-RNAi negative control group. CONCLUSION: Olig2 knockdown can promote the repair of hypoxic-ischemic brain damage in newborn rats.

[Predictive value of anti-mutated citrullinated vimentin antibody on one-year radiographic progression in patients with rheumatoid arthritis].

Objective: To investigate the value of baseline anti-mutated citrullinated vimentin (MCV) antibody for predicting one-year radiographic progression in patients with rheumatoid arthritis (RA). Methods: Consecutive RA patients were recruited from November 2014 to July 2018 at Department of Rheumatology, Sun Yat-sen Memorial Hospital, Clinical data were collected including disease activity score in 28 joints with four variables including C-reactive protein (CRP).Serum anti-MCV antibody at baseline was detected by enzyme-linked immunosorbent assay. X ray assessment of both hands/wrists was performed and assessed according to the Sharp/van der Heijde modified score (mTSS) at baseline and the 12th month. Univariate and multivariate logistic regression analyses were used to identify the risk factors for one-year radiographic progression. Results: Among 220 RA patients recruited, the positive rate of anti-MCV antibody at baseline was 77.7%. Compared with those with negative anti-MCV antibody, RA patients with positive anti-MCV antibody had higher disease activity score in 28 joints with four variables induding CRP [3.8 (2.4, 5.0) vs. 3.1 (2.1, 4.0), P=0.007], more physical dysfunction (21.6% vs. 8.2%, P=0.033) and higher radiographic indicators including mTSS [11 (2, 27) vs. 4 (1, 10), P=0.003], joint space narrowing [JSN, 4 (0, 14) vs. 2 (0, 6), P=0.024] and joint erosion[JE, 5 (1, 18)vs. 3 (0, 5), P=0.003]. After one-year follow-up, sixty-six RA patients (30.0%) developed radiographic progression, the percentage of whom was significantly higher in positive anti-MCV group than that in negative anti-MCV group (33.9% vs.16.3%, P=0.018). Multivariate logistic regression analysis suggested that positive anti-MCV antibody at baseline was an independent risk factor for one-year radiographic progression (OR=2.341, 95%CI 1.002-5.469). Conclusion: Positive anti-MCV antibody at baseline predicts one-year radiographic progression in RA patients. In the future, anti-MCV antibody can be used not only as a supplementary laboratory marker, but also in disease activity assessment and prognosis prediction for RA.

NLRP6-caspase 4 inflammasome activation in response to cariogenic bacterial lipoteichoic acid in human dental pulp inflammation.

AIM: To explore the presence and function of NLRP6-caspase 4 inflammasome in human pulp tissue and human dental pulp cells (HDPCs). METHODOLOGY: Pulp tissue was collected from freshly extracted human caries-free third molars and third molars with irreversible pulpitis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were performed to assess the expression of NLRP6-caspase 4 inflammasome. HDPCs were prepared from normal human pulp tissues and challenged with Porphyromonas gingivalis LPS. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were performed to assess if LPS can upregulate NLRP6 and caspase-4. HDPCs were further challenged with LPS followed with cytosolic Streptococcus mutans lipoteichoic acid (LTA). SiRNA targeting NLRP6 and Casp4 and pharmacology inhibitor Ac-FLTD-CMK and MCC950 were used to assess if Streptococcus mutans LTA can activate the NLRP6 but not the NLRP3 inflammasome. Western blot and ELISA were performed to evaluate inflammasome activation. The Student's t-test and one-way anova were used for statistical analysis. RESULTS: NLRP6-caspase 4 inflammasome was upregulated and activated in inflamed human dental pulp tissue. In HDPCs, Porphyromonas gingivalis LPS upregulated the expression of NLRP6, CASP1 and CASP4 in a type I interferon dependent manner. After LPS priming, cytosolic Streptococcus mutans LTA triggered NLRP6-caspase 4 inflammasome activation. Knockdown of NLRP6 or CASP4 using siRNA or using pharmacology inhibitor Ac-FLTD-CMK but not MCC950 efficiently suppressed inflammasome activation by cytosolic LTA. CONCLUSIONS: NLRP6-caspase 4 inflammasome may play an important role in pulp inflammation and immune defence. Inflammatory caspases represent a pharmacological target to restrain pulpal inflammation.

[Study on spatial clustering characteristics of tuberculosis in China, 2013-2018].

Objective: To explore the tuberculosis (TB) clustering areas and changing tendency in China from 2013 to 2018, so as to provide evidence for improving the control and prevention programs on TB. Methods: Spatial distribution of TB in China from 2013 to 2018 was studied using data from TB information management system of Chinese disease prevention and control information system. The SaTScan 9.6 software was used to detect and analyze the TB clusters and relative risks. Likelihood ratio and P value under the scan windows were used as the main index to define the clusters. Results: The TB registration rate declined in China from 2013 to 2018. High-risk clusters were mainly located in western regions of Xinjiang, Tibet, Shaanxi, Sichuan, Chongqing, Yunnan, Guizhou, Guangxi provinces and central and eastern regions of Inner Mongolia, Hubei, Hunan, Jiangxi, Guangdong and Hainan provinces. The number of counties with TB clusters declined slowly, from 1 112 in 2013 to 806 in 2018. In comparison with areas other than the clusters, the RR of TB in the clusters remained at high levels in southern Xinjiang and western Tibet from 2013 to 2018 (RR>3.0). Conclusions: The number of the counties with TB clustering declined slowly from 2013 to 2018, and most of them were located in western and central China. Early detection and health education should be focused on TB patients to prevent the spread of TB. Management programs set for TB patients should be strengthened, especially in the western parts of the country where TB clusters and high relative risks existed.

Differentially Expressed Homologous Genes Reveal Interspecies Differences of Paragonimus Proliferus based on Transcriptome Analysis.

Paragonimus proliferus (P. proliferus), one of 46 Paragonimus species registered in the National Center for Biotechnology Information database, may be much more widely distributed in Southeast Asia than previously thought, as its reported natural foci have increased in the past decades. However, very little is known about its molecular biology, especially at the transcriptome level. For the first time, the transcriptome of this species was sequenced and compared with four other common Paragonimus species, namely Paragonimus skrjabini, Paragonimus kellicotti, Paragonimus miyazakii, and Paragonimus westermani, to predict homologous genes and differentially expressed homologous genes to explore interspecies differences of Paragonimus proliferus. A total of 7393 genes were found to be significantly differentially expressed. Of these, 49 were considered to be core genes because they were differentially expressed in all four comparison groups. Annotations revealed that these genes were related mainly to "duplication, transcription, or translation", energy or nutrient metabolism, and parasitic growth, proliferation, motility, invasion, adaptation to the host, or virulence. Interestingly, a majority (5601/7393) of the identified genes, and in particular the core genes (48/49), were expressed at lower levels in P. proliferus. The identified genes may play essential roles in the biological differences between Paragonimus species. This work provides fundamental background information for further research into the molecular biology of P. proliferus.

[Ultrastructural study of ampulla of mouse inner ear].

Objective: To observe the ultrastructure of the ampulla, and analyze its physiological and pathological significance. Methods: In this study, 20 Kunming mice were used, and scanning electron microscopy was used to observe the ultrastructure of the ampulla of inner ear. Results: Otoconia was found among the cilia bundles of different haircell(intercilla otoconia of ampulla). The cupula was attached to the lateral wall of the ampulla, and easily to be separated; after separated, a kind of slender crystal(surface otoconia of ampulla) could be seen between the cupula and lateral wall of the ampulla, both sides of ampullary crest were covered with slender crystals too. On the canal side of the ampulla wall, there was more particulate matter attached to the wall near the bottom of ampullary crest, partially embedded in the wall, and less on the utricle side of the ampulla wall. Conclusions: The observation of the ultrastructure of the ampulla is helpful for better understanding the physiological functions of the semicircular canals and the ampulla, and better understanding the pathogenesis and solution of some vertigo diseases.

[Characteristics and clinical significance of body composition in gout patients].

Objective: To investigate the characteristics of body composition (BC) in gout patients and its clinical significance. Methods: Consecutive gout patients were recruited between August 2017 and December 2018. Demographic information, clinical characteristics and comorbidities were collected. BC was assessed by bioelectric impedance analysis including body fat percentage (BF%), trunk and limb BF%, appendicular skeletal muscle index. Overfat was defined by BF% ≥25% for male and ≥35% for female. The association between BC and serum uric acid (sUA) was evaluated by multiple linear regression. Results: A total of 362 gout patients were recruited with median age 38 (30, 52) years, 96.1% (348/362) were male. Mean sUA was (551±133) µmol/L. The mean BF% was (25.8±6.4)% with 53.6%(194/362) patients overfat. Male gout patients with overfat showed more affected joints [4(2, 6) vs. 2(2, 5)], higher sUA [(576±126)µmol/L vs. (523±134) µmol/L], higher prevalence of dyslipidemia [70.1%(131/187) vs. 54.0%(87/161)], metabolic syndrome [60.8%(118/187) vs. 28.0%(47/161)], fatty liver [58.2%(113/187) vs. 35.1%(59/161)] and hypertension [44.4%(83/187) vs. 25.5%(41/161)] than male patients with normal fat (all P<0.05). Their BF%, trunk BF% and limb BF% were positively correlated with the numbers of affected joints, sUA, metabolic syndrome, fatty liver, and hypertension, respectively (r=0.154-0.435, all P<0.05). Multivariable linear regression suggested that BF% (ß=4.29, P=0.020) and trunk BF% (ß=9.11, P=0.007), but not limb BF%, were positively correlated with sUA. Conclusion: Overfat is very common in gout patients. The proportion of trunk fat in male patients is positively correlated with sUA. When assessing obesity in gout patients clinically, body composition analysis should be performed simultaneously.

MiR-506 suppresses papillary thyroid carcinoma cell proliferation and metastasis via targeting IL17RD.

OBJECTIVE: The aim of this study was to determine the role of microRNA-506-3p (miR-506) in papillary thyroid carcinoma (PTC), and to further explore the underlying mechanism. PATIENTS AND METHODS: The expression level of miR-506 in clinical cases was detected by Real Time-fluorescence quantitative Polymerase Chain Reaction (RT-qPCR). Meanwhile, RT-qPCR was performed to determine miR-506 expression in different PTC cell lines. Bioinformatics software was used to predict the possible target genes of miR-506. Dual-Luciferase reporter gene assay together with Western blot (WB) assay were used to verify the prediction results. Finally, cellular functions such as proliferation and metastasis capacities were detected in vitro. RESULTS: RT-qPCR was used to measure the expression level of miR-506 in 80 paired PTC cases. The results showed that the expression level of miR-506 in PTC tissues was significantly decreased. In vitro, miR-506 expression was also markedly suppressed in four PTC cell lines. TPC-1 cells expressed the lowest level of miR-506. Subsequently, the target gene of miR-506 was predicted by TargetScan, miRBase and miRanda. The prediction results indicated that IL17RD was an alternative target gene of miR-506. Furthermore, miR-506 was found to remarkably inhibit the Luciferase activity of wild-type IL17RD. However, it had no effect on mutant-type. Besides, the protein expression level of IL17RD was significantly reduced in miR-506-overexpressing TPC-1 cells. More importantly, the restored expression of IL17RD could alleviate the blocking effects of miR-506 on cell proliferation, migration and invasion. CONCLUSIONS: In this study, we found that miR-506 could inhibit the proliferation and metastasis of PTC cells. Meanwhile, IL17RD might be a downstream target of the biological process. Our findings provided a new therapeutic direction for the treatment of PTC.