[Effects of Dapagliflozin on contrast-induced acute kidney injury in patients with type 2 diabetes mellitus underwent percutaneous coronary intervention].

Objective: To investigate the effect of Dapagliflozin, sodium-glucose cotransporter 2 inhibitor (SGLT2i), on contrast-induced acute kidney injury (CIAKI) in patients with type 2 diabetes mellitus (T2DM) after percutaneous coronary intervention(PCI). Methods: A cohort study. The clinical data of 366 patients with coronary heart disease combined with T2DM who underwent PCI in the Department of Cardiology, Tianjin University Chest Hospital, from June 2021 to June 2022 were retrospectively analyzed, including 218 males and 148 females, aged (64.6±11.0) years old. According to whether the patients had used Dapagliflozin or not, the selected patients were divided into SGLT2i group(n=124) and control group(n=242). The changes in cardiac indicators, renal function, and inflammatory response indicators before and 72 hours after PCI treatment were analyzed and compared between the two groups. The incidence rate of CIAKI in the two groups was analyzed, and the influencing factors of CIAKI were analyzed by multivariate logistic regression. The major adverse cardiac events (MACE) were recorded during the follow-up period of the two groups, and Kaplan-Meier survival analysis and log-rank test were used to compare the differences in MACE occurrence between the two group. Results: The left ventricular ejection fraction (LVEF) of the SGLT2i group was lower than that of the control group, and the proportion of patients with LVEF<45% and CIAKI risk score were higher than those of the control group, with statistical significance (all P<0.05). 72 h after PCI treatment, ß-2 Microglobulin(ß-2MG), cystatin-C(Cys-C), and neutrophil gelatinase-associated lipocalin (NGAL) in both groups were all increased compared to those before PCI treatment, with statistical significance (all P<0.05).ß-2MG, Cys-C, and NGAL in SGLT2i group were all lower than those in the control group, with statistical significance(all P<0.05).The levels of interleukin-6(IL-6), hypersensitive C-reactive protein (hs-CRP), and malondialdehyde in both groups of patients increased compared to preoperative levels, while the levels of superoxide dismutase (SOD) decreased compared to preoperative levels, with statistical significance (all P<0.05). The levels of IL-6, hs-CRP, and malondialdehyde in the SGLT2i group were lower than those in the control group, while SOD was higher than that in the control group, with statistical significance (all P<0.05). Among all patients included, 34 cases experienced CIAKI (9.8%), and the incidence of CIAKI in the SGLT2i group was lower than that in the control group [4.8% (6/124) vs 11.6% (28/242),P=0.037]. Multivariate logistic regression analysis showed that the use of dapagliflozin was a protective factor for CIAKI in T2DM patients receiving PCI treatment (OR=0.321, 95%CI: 0.127-0.816, P=0.017). After a follow-up of 14.0 (12.0, 16.2) months, the incidence of MACE in SGLT2i group was lower than that in the control group (7.3% vs 12.8%, P=0.048). Conclusions: Dapagliflozin may reduce the risk of CIAKI and MACE in T2DM patients after PCI treatment. Its mechanism may be related to the anti-inflammatory and antioxidant effects of SGLT2i.

Genetic analysis of health traits and their associations with longevity, fertility, production, and conformation traits in Holstein cattle.

Health traits have high economic values in dairy cattle breeding, which can cause considerable financial loss through involuntary culling. In this study, fourteen health traits were analysed, including five composite health traits: reproductive disorders, udder health (UH), digestive disorders, metabolic disorders, locomotory diseases (LD), and nine independent health traits: gestation disorders and peripartum disorders, irregular estrus cycle and sterility, metritis (ME), mastitis (MA), abomasal displacement (AD), enteritis (EN), and ketosis, claw diseases (CD), laminitis complex. This study analysed variance components for health traits through both single and bivariate repeatability animal models. All health traits showed low heritability, ranging from 0.001 to 0.025. Most of the health traits in five categories showed negative genetic correlations, ranging from -0.012 (CD and EN) to -0.634 (ME and EN). Strong positive genetic correlations appeared within the same category, ranging from 0.469 (EN and AD) to 0.994 (UH and MA, LD and CD). Furthermore, approximate genetic correlations were evaluated between health traits and routinely collected traits (longevity, fertility, production, and conformation). In general, the low to moderate approximate genetic correlations were estimated between health traits and routinely collected traits. The estimated correlations between health traits and longevity, fertility, production, and conformation traits could provide an indirect reference for disease-resistance breeding in Holstein cattle.

[Development in diagnostic criteria for allergic bronchopulmonary aspergillosis].

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic lung disease caused by the sensitization of Aspergillus fumigatus. In recent years, the research into ABPA has progressed, the testing methods have improved and the diagnostic criteria have been continuously updated. There is no gold standard for the diagnosis of the disease. The diagnostic criteria for ABPA include predisposing diseases, fungal-related immunoassay and pathological examination. Understanding the clinical significance of ABPA diagnostic criteria may help to prevent irreversible bronchopulmonary injury, improve respiratory function and improve the prognosis of patients.

Genetic analysis of longevity and their associations with fertility traits in Holstein cattle.

The increase of longevity is intended to reduce involuntary culling rates, not extend the life span, and it reflects the ability of animals to successfully cope with the environment and disease during production. Sire model, animal model and repeatability animal models were used to estimate the (co) variance components of longevity and fertility traits. Six longevity and thirteen fertility traits were analysed, including herd life (HL), productive life (PL), number of days between first calving and the end of first lactation or culling (L1); number of days between first calving and the end of the second lactation or culling (L2); number of days between first calving and the end of the third lactation or culling (L3); number of days between first calving and the end of the fourth lactation or culling (L4); age at first service, age at first calving (AFC), the interval from first to last inseminations in heifer (IFLh), conception rate of first insemination in heifer, days open (DO), calving interval, gestation length, interval from calving to first insemination (ICF), interval from first to last inseminations in cow (IFLc), conception rate of first insemination in cow, calving ease (CE), birth weight, and calf survival. The estimated heritabilities (±SE) were 0.018 (±0.003), 0.015 (±0.003), 0.049 (±0.004), 0.025 (±0.003), 0.009 (±0.002) and 0.011 (±0.002) for HL, PL, L1, L2, L3 and L4, respectively. Strong correlations were appeared in HL and PL; the genetic and phenotypic correlation coefficients were 0.998 and 0.985, respectively. There were high genetic and phenotypic correlations which were observed in L1 and L2, L2 and L3, L3 and L4, respectively. All fertility traits of heifer showed medium to high heritability, while the cow showed low heritability. All heifer fertility traits had low genetic associations with longevity traits, ranging from -0.018 (L2 and IFLh) to 0.257 (L3 and AFC). Most of the fertility traits showed negative correlations with longevity traits in different parities, and we recommend DO, ICF, IFLc and CE as indirect indicators of longevity traits in dairy cows, but we also need to take into account the differences between parities.

[Application status of CFD technology in occupational hazard control].

In the process of occupational hazard management, computational fluid dynamics technology can be used to reflect the distribution pattern of occupational hazards in the production process, so as to quickly and accurately guide the formulation of occupational disease prevention and control programs. This paper summarizes and analyzes the current research results on the prevention and control of occupational hazards in workplaces through computational fluid dynamics technology, and describes the application of these research results in the process of occupational disease prevention and control. On this basis, this paper presents the problems and application limitations of existing research and points out the future key research directions, which are of great reference value for guiding further systematic and in-depth research on simulation, experimentation and management of occupational hazards that can cause occupational diseases.

[Feasibility analysis of CT angiography derived computational fluid dynamics in evaluating intracranial artery stenosis].

A retrospective study was performed on 8 patients, including 7 males and 1 female, aged 47 to 77 (59±3) years, with intracranial artery stenosis in General Hospital of Eastern Theater Command from November 2018 to May 2019, who underwent CT angiography (CTA), digital subtraction angiography (DSA) and invasive fractional flow reserve (FFR) assessment. Three-dimensional (3D) prototyping models of intracranial artery based on image data of CTA was constructed and the hemodynamic parameters were obtained using computational fluid dynamics methods. The results showed that CT-FFR value was 0.59±0.18, and invasive FFR value was 0.60±0.22, from which we propased that noninvasive hemodynamic analyses can be used to evaluate the physiological significance of intracranial arterial stenosis.

[Survival analysis of unexpected small cell lung cancer following surgery].

Objective: To investigate the survival and influencing factors of unexpected small cell lung cancer following surgery. Methods: We respectively reviewed the clinical characters of 104 patients who underwent surgical treatment and be proved as small cell lung cancer by pathology between January 2000 to October 2020 in Chinese PLA General Hospital. Overall survival (OS) of patients was evaluated using Kaplan-Meier and Cox proportional hazards analysis. Results: Of 104 patients, 27 cases showed central lesions, and other 77 showed peripheral nodules. The margin of nodules was smooth in 42 cases on CT imaging. The median OS was 34.3 months and 5-year OS rate was 45.8%. Postoperative 5-year OS rates for patients were 52.1%, 45.4%, and 27.8% for clinical stages Ⅰ, Ⅱ, and Ⅲ, respectively. Univariate analyses identified the age, surgical access, surgical approach, N stage, TNM stage and vascular cancer emboli were associated with OS (P<0.05). The N stage was an independent factor for the OS of patients (P<0.05). Conclusions: Patients with unexpected SCLC, including Ⅰ, Ⅱ and part ⅢA stage have favorable outcome and can benefit from surgery and systemic postoperative treatment. Standard lobectomy plus systemic lymph node dissection is commended.

[Effects of NLRP3-mediated pyroptosis on olfaction dysfunction in allergic rhinitis].

Objective: To explore the relationship between NLRP3-mediated pyroptosis and olfactory dysfunction (OD) in allergic rhinitis (AR), and to evaluate the therapeutic potential of CY-09, a selective NLRP3 inhibitor for OD. Methods: An AR mouse model was established with ovalbumin, and the olfactory function of AR mice was detected by the buried food pellet test. Mice with OD were intraperitoneally injected with CY-09 or saline. The activation of microglia and astrocytes in olfactory bulb was detected by immunohistochemistry. The expression level of pyroptosis associated protein was detected by Western blot. The level of pyroptosis associated proinflammatory factor mRNA was determined by real-time PCR. SPSS 24.0 software was used for statistical analysis. Results: After the test, ovalbumin successfully established AR mice model, in which 52.5% (21/40) of them showed OD. The number of activated microglia and astroglia in olfactory bulb tissue in OD group were more than those in non-OD group (all P<0.05). Compared with the control group, the expression of NLRP3, caspase-1 and gasdermin D (GSDMD) was significantly increased in the olfactory bulb of the OD group (all P<0.05). CY-09 could significantly reduce the level of NLRP3, caspase-1, GSDMD, IL-1ß and IL-18 expression, and inhibite the activation of microglia and astrocytes in the olfactory bulb tissues (all P<0.05). Conclusion: NLRP3-mediated pyroptosis is closely related to the OD associated with AR. CY-09 could improve the olfactory function in AR mice, which may be related to blocking the NLRP3-mediated pyroptosis.

Genome-wide scanning for CHD1L gene in papillary thyroid carcinoma complicated with type 2 diabetes mellitus

Purpose Papillary thyroid carcinoma (PTC) represents the most common subtype of thyroid cancer (TC). This study was set out to explore the potential effect of CHD1L on PTC and type 2 diabetes mellitus (T2DM). Methods We searched for T2DM susceptibility genes through the GWAS database and obtained T2DM-related differentially expressed gene from the GEO database. The expression and clinical data of TC and normal samples were collated from the TCGA database. Receiver operating characteristic (ROC) curve analysis was subsequently applied to assess the sensitivity and specificity of the CHD1L for the diagnosis of PTC. The MCP-counter package in R language was then utilized to generate immune cell score to evaluate the relationship between CHD1L expression and immune cells. Then, we performed functional enrichment analysis of co-expressed genes and DEGs to determine significantly enriched GO terms and KEGG to predict the potential functions of CHD1L in PTC samples and T2DM adipose tissue. Results From two genes (ABCB9, CHD1L) were identified to be DEGs (p < 1 * 10−5) that exerted effects on survival (HR > 1, p < 0.05) in PTC and served as T2DM susceptibility genes. The gene expression matrix-based scoring of immunocytes suggested that PTC samples with high and low CHD1L expression presented with significant differences in the tumor microenvironment (TME). The enrichment analysis of CHD1L co-expressed genes and DEGs suggested that CHD1L was involved in multiple pathways to regulate the development of PTC. Among them, Kaposi sarcoma-associated herpesvirus infection, salmonella infection and TNF signaling pathways were highlighted as the three most relevant pathways. GSEA analysis, employed to analyze the genome dataset of PTC samples and T2DM adipose tissue presenting with high and low expression groups of CHD1L, suggests that these differential genes are related to chemokine signaling pathway, leukocyte transendothelial migration and TCELL receptor signaling pathway (AU)

[Predictive diagnostic value of serum 25-hydroxyvitamin D3 in eosinophilic chronic rhinosinusitis with nasal polyps].

Objective: To compare the value of 25-hydroxyvitamin D3 (25-(OH)D3) with other clinical parameters in the prediction and diagnosis of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). Methods: Eligible chronic rhinosinusitis with nasal polyps (CRSwNP) patients and healthy subjects in the Affiliated Hospital of Guizhou Medical University from January to April of 2021 were included for this study. The age, gender, past history and other basic characteristics of all subjects were recorded. The CRSwNP patients were classified into ECRSwNP and non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP) endotypes by the percentage of tissue eosinophils. Serum 25-(OH)D3 levels measurements were performed in all subjects. Paranasal sinus CT scans, blood eosinophil counts, and determination of total immunoglobulin E (total IgE), Th1/Th2 plasma cytokines and nasal nitric oxide (nNO) levels were performed before surgery. Logistic regression analysis was used to evaluate the related factors of ECRSwNP. Receiver operating characteristic (ROC) curves was used to evaluate the predictive potential of the clinical parameters. Results: One hundred and twenty-seven CRSwNP patients and 40 healthy subjects were recruited, including 74 males and 93 females of the patients, with the age of (38.73±13.05) years. In patients with ECRSwNP, serum 25-(OH)D3 levels were significantly lower than those in nECRSwNP patients ((26.14±4.58) ng/ml vs (35.71±7.86) ng/ml, t=-8.564, P<0.01). The prevalence of asthma, prevalence of allergic rhinitis, peripheral blood eosinophil counts, total IgE levels, nNO levels and CT scores ratio for ethmoid sinus and maxillary sinus (E/M ratio) of ECRSwNP patients were significantly higher than those in nECRSwNP patients (all P<0.05). However, there was no significant difference in Th1/Th2 cytokines levels between the histological types of CRSwNP (all P>0.05). Among the predictive indicators, 25-(OH)D3 had the highest predictive value, with ROC area under curve (AUC) value of 0.882. The best cut-off point of 28.5 ng/ml for 25-(OH)D3 demonstrated a sensitivity of 0.871 and a specificity of 0.762 for ECRSwNP. Conclusion: Measurement of serum 25-(OH)D3 level may be used as an effective method to distinguish between ECRSwNP and nECRSwNP.

Genome-wide scanning for CHD1L gene in papillary thyroid carcinoma complicated with type 2 diabetes mellitus.

PURPOSE: Papillary thyroid carcinoma (PTC) represents the most common subtype of thyroid cancer (TC). This study was set out to explore the potential effect of CHD1L on PTC and type 2 diabetes mellitus (T2DM). METHODS: We searched for T2DM susceptibility genes through the GWAS database and obtained T2DM-related differentially expressed gene from the GEO database. The expression and clinical data of TC and normal samples were collated from the TCGA database. Receiver operating characteristic (ROC) curve analysis was subsequently applied to assess the sensitivity and specificity of the CHD1L for the diagnosis of PTC. The MCP-counter package in R language was then utilized to generate immune cell score to evaluate the relationship between CHD1L expression and immune cells. Then, we performed functional enrichment analysis of co-expressed genes and DEGs to determine significantly enriched GO terms and KEGG to predict the potential functions of CHD1L in PTC samples and T2DM adipose tissue. RESULTS: From two genes (ABCB9, CHD1L) were identified to be DEGs (p < 1 * 10-5) that exerted effects on survival (HR > 1, p < 0.05) in PTC and served as T2DM susceptibility genes. The gene expression matrix-based scoring of immunocytes suggested that PTC samples with high and low CHD1L expression presented with significant differences in the tumor microenvironment (TME). The enrichment analysis of CHD1L co-expressed genes and DEGs suggested that CHD1L was involved in multiple pathways to regulate the development of PTC. Among them, Kaposi sarcoma-associated herpesvirus infection, salmonella infection and TNF signaling pathways were highlighted as the three most relevant pathways. GSEA analysis, employed to analyze the genome dataset of PTC samples and T2DM adipose tissue presenting with high and low expression groups of CHD1L, suggests that these differential genes are related to chemokine signaling pathway, leukocyte transendothelial migration and TCELL receptor signaling pathway. CONCLUSION: CHD1L may potentially serve as an early diagnostic biomarker for PTC, and a target of immunotherapy for PTC and T2DM.

Dietary Lactobacillus casei can be used to influence intraepithelial lymphocyte migration and modulate mucosal immunity in chicks.

1. The role of probiotics in modulating intestinal mucosal immunity in chicks was investigated by measuring migration of intraepithelial lymphocytes (IEL) and cytokine signals in chicks fed on a diet supplemented with the Lactobacillus casei compared with those of chicks fed on an unsupplemented diet.2. Increased numbers of intraepithelial lymphocytes (IEL) were detected in the ileal epithelium at d 3 and d 7 after feeding a diet containing 108 CFU/g L. casei.3. Greater expression of chemokine genes for C-C motif chemokine ligand 3, C-X-C motif chemokine ligand 12, C-C motif chemokine receptor 5, and C-C motif chemokine receptor 9 were detected in the ileum on d 3, suggesting a greater number of IEL was associated with lymphocyte migration through the chemokine signalling pathway.4. After IEL migration, cell proliferation was evident in mucosal epithelial cells on d 14. Evidence of immune responses induced in the ileum from d 3-21 after feeding the diet containing L. casei was shown by the significant (P < 0.05) differences in transforming growth factor-ß, secretory immunoglobulin A, interferon-γ, tumour necrosis factor-α, interleukin-4, and interleukin-10.5. These results indicated that feeding L. casei helps guide IEL migration and modulates intestinal mucosal immunity.

Circ_0056618 promoted cell proliferation, migration and angiogenesis through sponging with miR-206 and upregulating CXCR4 and VEGF-A in colorectal cancer.

OBJECTIVE: Growing evidence has revealed that circular RNAs (circRNAs) play important roles in the development of cancers, including colorectal cancer (CRC). In this study, we mainly focused on the expression of circ_0056618 and potential functions of circ_0056618 in CRC patients. PATIENTS AND METHODS: RT-PCR was performed to detect circ_0056618 and miR-206 expressions in CRC tissues and adjacent non-tumor tissues. Correlation analysis was used to analyze the correlation between circ_0056618 and miR-206. Kaplan-Meier method was conducted to analyze the overall survival (OS) for CRC patients. Moreover, CCK-8 assay was used to measure cell proliferation ability and transwell assay was performed to detect cell migration ability. Besides, tube formation assay was performed to measure cell angiogenesis capacity. Western blot (WB) was performed to measure protein levels of tissues samples and CRC cell lines. Notably, the Luciferase reporter assay was performed to prove the binding sites in circ_0056618 with miR-206, miR-206 with CXCR4 and VEGF-A. RESULTS: We found that circ_0056618 was elevated in CRC tumor tissues and CRC cell lines, which was related to poor diagnosis for CRC patients. MiR-206 was reduced in CRC tissues, which was negatively related with circ_0056618. Protein levels of CXCR4 and VEGF-A were elevated in CRC tumor tissues, which were negatively related with miR-206. Circ_0056618 inhibition inhibited proliferation, angiogenesis and migration of HT29 cells, and repressed protein levels of Cyclin D1, VEGF-A and N-cadherin and increased E-cadherin. Notably, Luciferase reporter assay indicated that circ_0056618 could sponge with miR-206, which could directly target at CXCR4 and VEGF-A. Finally, we proved a pathway that circ_0056618 promoted cell proliferation, migration and angiogenesis through sponging with miR-206 and removing the repressing effects of miR-206, thereby upregulating CXCR4 and VEGF-A in CRC. CONCLUSIONS: Above all, this study revealed that circ_0056618 was increased in CRC tissues, which was related with the poor OS of CRC patients. We found that circ_0056618 could promote cell proliferation, migration and angiogenesis through sponging with miR-206 and upregulating CXCR4 and VEGF-A in CRC, which might provide a novel potential therapeutic target for treating CRC.

[Clinical features and prognostic factors of primary gastric neuroendocrine neoplasms].

Objective: To study the clinical characteristics and classification of gastric neuroendocrine neoplasm(NEN) and prognostic factors of mixed adenoneuroendocrine carcinoma (MANEC) and gastric neuroendocrine carcinoma(NEC). Methods: A total of 148 gastric NENs were divided into type Ⅰ, type Ⅱ and type Ⅲ based on the classification of European Neuroendocrine Tumor Society (ENETS). Kaplan-Meier test and Cox regression model were used in univariate and multivariate survival analysis in 108 cases with pathological G3 gastric NEN. Results: In this study, the percentages of type Ⅰ, type Ⅱ and type Ⅲ were 25.0%(37), 3.4%(5) and 71.6%(106) respectively. Among type Ⅰ patients, 28(75.7%) lesions were located in gastric fundus or body, 29(78.4%) had bumps. Lymph node involvement was found in 4 (10.8%) patients. Twenty-six (70.3%) patients received endoscopic treatment and 11 (29.7%) with surgery. All 5 type Ⅱ patients presented lesions in gastric fundus or body, including 4 with ulcers, who were all treated by endoscope. Three type Ⅱ patients had gastrinoma, and 2 combined with multiple endocrine neoplasmⅠ. In type Ⅲ patients, 56(52.8%) showed ulcerative lesions. The majority of patients (102, 96.2%) had a single lesion, 94(88.7%) with lymph node or other organ metastasis. In this study, no deaths were reported in gastric NEN with a pathological grade of G1 or G2. The mortality rate was 38.9%(42/108) in patients with G3 NEN. Survival analysis suggested that age, metastasis of tumor were associated with poor prognosis (P=0.041, 0.025). Conclusions: Patients with gastric NEN have heterogenous clinical presentations according to gender, age, endoscopic features, infiltration and metastasis, and pathological grade. Aging and metastasis are negative prognostic factors of G3 gastric NEN.

The prognostic role of FZD6 in esophageal squamous cell carcinoma patients.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a kind of cancer with heterogeneous biological characteristics, which is affected by a complex network of gene interactions. Identification of molecular biomarkers paves the way for individualized therapy based on gene expression profiles, which can overcome the heterogeneity of ESCC. METHODS: In this study, GSE20347, GSE23400 and GSE45670 datasets were retrieved from Gene Expression Omnibus (GEO) database, and the overlapping differentially expressed genes (DEGs) in three datasets were screened. Then the overlapping DEGs function was annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis. The prognostic value of the top five KEGG pathway-related genes were further validated in The Cancer Genome Atlas (TCGA) database. After extensive statistical analysis, four genes (CDC25B, CXCL8, FZD6 and MCM4) were identified as potential prognostic markers. Among the four candidate genes, the prognostic value of FZD6 in ESCC patients has not been evaluated. Therefore, we finally used immunohistochemistry method to evaluate the effect of FZD6 on the prognosis of patients with ESCC. Additionally, we detected the expression level of FZD6 in ESCC cell line and normal esophageal epithelial cell line, and observed the cell viability of ESCC cell line after FZD6 knockdown. RESULTS: The results showed that the overexpression of FZD6 predicted poor overall survival (OS) (P = 0.005) and progression-free survival (PFS) (P = 0.004) in ESCC patients. COX regression analysis showed that N stage (P = 0.026) and FZD6 expression level (P = 0.001) were independent prognostic factors of OS for ESCC patients. Furthermore, compared with normal esophageal epithelial cell line, the up-regulation of FZD6 was detected in ESCC cell line. Knockdown of FZD6 could significantly inhibit the proliferation of ESCC cells (P < 0.001). CONCLUSION: CDC25B, CXCL8, FZD6 and MCM4 were screened as candidate genes for prognosis assessment of patients with ESCC. The prognostic role of FZD6 in ESCC patients was confirmed in current study.

[Clinical characteristics analysis of 1 808 rheumatism in-patients with oral candidiasis].

Objective: To analyze the clinical characteristics of oral candidiasis (OC) in in-patients with rheumatism, in order to provide theoretical basis for the prevention and treatment of OC in rheumatism patients. Methods: One thousand eight hundred and eight in-patients were recruited in the Department of Rheumatology, the Second Hospital of Shanxi Medical University from January 2017 to December 2017. The patients included 607 males and 1 201 females. Their average age was (49.5±15.5) years old with a ranging from 14 to 81 years. According to occurrence of OC or not, the patients were divided into OC group and non-OC group. The differences of general data, primary diseases, laboratory examinations, usage of glucocorticoid and immunosuppressant therapy were compared between the two groups, and the risk factors of OC occurrence were analyzed. Results: Two hundred and sixty-nine patients had OC and 1 539 patients had no OC. Age [(54.9±14.7) years], duration of illness [(9.4±4.4) years] and hospital stay [(15.3±5.7) d] in OC group were significantly longer than those in non-OC group. OC incidence in patients with connective tissue disease (CTD) [17.40% (193/1 109)] was higher than that in non-CTD patients [10.87% (75/699)] (P<0.001). OC most likely occurred in patients with such CTD as Sjögren syndrome (SS) and Behcet syndrome. OC incidence in non-CTD patients with osteoarthritis (OA) was highest. The salivary flow rate in OC group [(0.65±0.45) ml/min] was significantly lower than that in non-OC group [(0.78± 0.39) ml/min] (t=2.394, P=0.017). There was no statistical differences in other laboratory examinations between the two groups, including white blood cells (WBC), lymphocyte, platelet count, liver function, renal function, erythrocyte sedimentation rate, C-reactive protein, procalcitonin, immunoglobulin G, immunoglobulin M, immunoglobulin A, C(3), C(4) and so on. OC incidence in patients using prednisone≥15 mg/d [17.16% (133/775)] was higher than that in patients using prednisone<15 mg/d [12.53% (94/750)] and patients not using prednisone [14.84% (42/283)] (P<0.05). The incidence of OC in patients with immunosuppressant therapy [16.11% (226/1 403)] was statistically higher than that in non-immunosuppressant patients [10.62% (43/405)] (P<0.01). Logistic regression analysis showed that the risk factors of OC occurrence included primary diseases (P<0.001), age (P<0.001), duration of illness (P=0.001) and duration of hospitalization (P=0.002). Conclusions: OC occurred commonly in rheumatism in-patients, especially in elder patients, patients with long duration of illness and hospital stay. OC incidence in CTD patients is significantly higher than that in non-CTD patients. Glucocorticoid and immunosuppressant therapy might significantly reduce the anti-fungal immunity of the patients.

The predictive and prognostic significance of liquid biopsy in advanced epidermal growth factor receptor-mutated non-small cell lung cancer: A prospective study.

OBJECTIVE: To determine the predictive and prognostic roles of three blood-based biomarkers: circulating tumour DNA (ctDNA), circulating tumour cells (CTC) and carcinoembryonic antigen (CEA), in patients with advanced epidermal growth factor receptor-mutated (EGFR+) lung cancer. MATERIALS AND METHODS: We recruited 28 patients with 103 serial blood samples. We performed mutational analyses for EGFR mutations using droplet digital PCR (ddPCR) on ctDNA. We evaluated the accuracy of EGFR mutation detection in ctDNA compared with tissue biopsy. We also quantified CTCs, ctDNA and CEA in serially collected blood samples, and evaluated the baseline and changes in these blood-based biomarkers with clinical outcomes. RESULTS: EGFR mutation detection in plasma was highly concordant as compared with tissue biopsy. Detectable baseline ctDNA was associated with higher disease burden (p < 0.01). Early disappearance of ctDNA at 4 weeks was associated with radiological response at 12 weeks of treatment (p = 0.01) and improved progression free survival (PFS) (HR 5.47, 95%CI 1.32-22.72, p = 0.02) and overall survival (OS) (HR 5.46, 95%CI 1.28-23.22, p = 0.02). A decrease in CTC count at 4 weeks was associated with improved PFS (HR 3.81, 95%CI 1.13-12.79, p = 0.03) but not OS. 85% of patients with radiological progression had a ctDNA rise compared with 22% of patients with stable disease (p=0.01). ctDNA rise was seen on average 170 days prior to radiological progression. There is a significant association between the rise of CEA level with radiological progression (p=0.001). CONCLUSION: Early change in ctDNA, CTC and CEA levels may be long-term predictors of treatment benefit and failure prior to availability of radiological response data.

Mechanisms of Toxicity and Cardiotoxicity of Alcohol Extract from Root, Stem and Leaf of Chloranthus Serratus.

ABSTRACT: Objective To compare the differences of cardiotoxicity of alcohol extract from root, stem and leaf of Chloranthus serratus in the rats, and discuss preliminarily its mechanism of toxicity. Methods Rats were randomly divided into four groups: blank, root alcohol, stem alcohol and leaf alcohol, with 8 in each group. After 14 days of continuous intragastric administration, the body mass change curves were drawn. The cardiac coefficient was calculated. The contents of creatine kinase （CK）, creatine kinase isoenzyme （CK-MB）, lactate dehydrogenase （LDH） and α-hydroxybutyrate dehydrogenase （α-HBDH） as well as the content changes of oxidative stress indexes - total superoxide dismutase （T-SOD） and malondialdehyde （MDA） in the serum of rats were detected. The cardiac pathomorphology changes in the rats were observed. The expression of intercellular adhesion molecule （ICAM-1） and heme oxygenase （HO-1） in myocardial tissue was detected. Results Body mass growth rate： stem alcohol group was the smallest, followed by leaf alcohol group. The difference of cardiac coefficient of every group had no statistical significance （P>0.05）. The myocardial tissues of stem alcohol group suffered the most serious damage, followed by the leaf alcohol group. The contents of CK, CK-MB, LDH and α-HBDH in stem alcohol group increased （P<0.05）. The increase of MDA content and decrease of T-SOD content in stem alcohol group had statistical significance compared with the blank group and root alcohol group, while the leaf alcohol group only had statistical significance in the decrease of T-SOD content compared with the blank group （P<0.05）. The positive expression of ICAM-1 enhanced and the expression of HO-1 protein decreased in every group after the intervention of different extracts. The change trend was stem alcohol > leaf alcohol > root alcohol group. Conclusion The alcohol extract from the stem has the highest cardiotoxicity, followed by the leaf extract, and its mechanism of toxicity may be related to oxidative stress.

Phosphorylation of AKT serine/threonine kinase and abundance of milk protein synthesis gene networks in mammary tissue in response to supply of methionine in periparturient Holstein cows.

The main objective was to evaluate the effect of increasing the supply of Met around parturition on abundance and phosphorylation of insulin- and mechanistic target of rapamycin complex 1 (mTORC1)-related signaling proteins along with mRNA abundance of milk protein and fat synthesis-related genes in postpartal mammary tissue. A basal control diet (control) or the basal diet plus ethyl-cellulose rumen-protected Met (0.9 g/kg of dry matter intake; Mepron, Evonik Nutrition & Care GmbH, Hanau-Wolfgang, Germany) were fed (n = 30 cows/diet) from d -28 to 60 relative to parturition. Mammary tissue and blood plasma were harvested from the same cows (n = 5/diet) in the control and Met groups at d 21 postpartum for mRNA, protein, and AA analysis. Increasing the supply of Met led to greater milk protein percentage and milk yield along with greater ratio of phosphorylated (p-)AKT to total AKT. The ratio of p-mTORC1 to total mTORC1 did not differ, but ratio of p-RPS6 to total ribosomal protein S6 (RPS6) was lower in response to Met supply. These responses were associated with greater mRNA abundance of the signaling proteins Janus kinase 2 (JAK2) and insulin receptor substrate 1 (IRS1). Greater Met supply also upregulated mRNA abundance of high-affinity cationic (SLC7A1) and sodium-coupled AA transporters (SLC38A1, SLC38A2); leucyl-tRNA (LARS), valyl-tRNA (VARS), and isoleucyl-tRNA synthetases (IARS); glucose transport solute carrier family 2 member 3 (SLC2A1); glucose transport solute carrier family 2 member 3 (SLC2A3); and casein α-s1 (CSN1S1). The mRNA abundance of components of the unfolded protein response, such as x-box binding protein 1 (XBP1) and activating transcription factor 6 (ATF6), were upregulated, and protein phosphatase 1, regulatory subunit 15A (PPP1R15A) was downregulated in response to greater Met supply. Overall, the data suggest that increased dry matter intake, greater phosphorylation status of AKT, upregulation of glucose and AA transporters, and transcripts of tRNases in response to enhanced Met supply might have compensated for a reduction in ribosome biogenesis due to a lower ratio of p-RPS6 to total RPS6. Together, these cellular responses constitute a mechanism whereby Met supply can regulate milk protein synthesis in early lactation.

[Clinical evaluation of gallbladder and common bile duct stones treated though cholecystostomy tube].

Objective: To investigate the efficacy, feasibility and safety of treatment of gallbladder and common bile duct stones treated through cholecystostomy tube. Methods: The clinical data of 17 patients with gallbladder and common bile duct stones treated through cholecystostomy tube from January 2012 to December 2016 was analyzed retrospectively. Results: Seventeen patients were successfully treated with percutaneous transhepatic gallbladder (PTGD), and 88.2% (15/17) patients had clinical symptom relief. There was no complication happened after PTGD and fistula expansion. All the stones were removed and there was 11.7% (2/17) of gallbladder bleeding, 5.9% (1/17) of pancreatitis, and 5.9% (1/17) of hyperamylasemia after stones extraction. The patients had gone through an average treatment period of 87.8±16.0 days, hospitalization of 5.5±0.6 times and 43.3±4.5 days, cost of 60.0±8.0 thousand, 6.9±0.9 operations, 1.4±0.6 stone extraction operations with the average time of 58.4±21.2 min. The duodenal papillary balloon dilatation rate was 82.4% (14/17). Conclusion: The treatment through cholecystostomy tube is an effective, safe and feasible technique for gallbladder and common bile duct stones. However, there are many shortcomings such as long treatment cycle, large number of hospitalization and operations, difficult operation and high cost.