[Preparation of interleukin-1ß-targeted nanobodies and their effects on apoptosis in hypoxic cardiomyocytes of mice].

Objective: To prepare interleukin-1ß-targeted nanoantibodies and observe their effects on apoptosis in hypoxic cardiomyocyte of mice. Methods: Using DNA recombination technology, the pET-16b and pHEN1 expression vectors were used to construct the prokaryotic expression plasmids of interleukin-1ß-targeted nanobodies (pET-16b-4G6M-VHH, pET-16b-5BVP-VHH, pET-16b-5MVZ-VHH, pHEN1-4G6M-VHH, pHEN1-5BVP-VHH and pHEN1-5MVZ-VHH, where VHH is a variable domain of heavy chain antibody, 4G6M-VHH, 5BVP-VHH, 5MVZ-VHH were three interleukin-1ß-targeted nanoantibodies respectively). The constructed plasmids were transferred into Escherichia coli Rosetta2 (DE3) for induction of expression and nickel column purification, respectively. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting were employed to identify the expression product and purified product, and the enzyme-linked immune sorbent assay (ELISA) was performed to determine their affinity. The cardiomyocyte hypoxia model was used with the highest affinity IL-1ß-targeted nanobody (pHEN1-5MVZ-VHH), and cell survival and apoptosis rates were detected (the experiment was divided into normal control group, hypoxia model group, blank plasmid group and 12.5, 25.0, 50.0 µg/ml pHEN1-5MVZ-VHH treatment groups). Results: SDS-PAGE and Western blotting results showed that the anti-interleukin-1ß (IL-1ß) nanobodies with a relative molecular mass of about 15 000 were successfully obtained. Likewise, ELISA results found that the nanobodies expressed in pHEN1 vector group had higher affinity for IL-1ß antigen compared with pET-16b vector group (4G6M-VHH group: 3.20±0.03 vs 1.20±0.03, P<0.001; 5BVP-VHH group: 3.18±0.06 vs 1.21±0.02, P<0.001; 5MVZ-VHH group: 3.38±0.05 vs 1.62±0.04, P<0.001). Additionally, the results of cell survival assay and apoptosis assay detected that compared with the hypoxia model group, HL-1 cell activity was significantly increased in the 25.0 µg/ml and 50.0 µg/ml pHEN1-5MVZ-VHH treatment groups [(75.55±2.23)% vs (46.90±2.51)%, P<0.001; (74.36±1.96)% vs (46.90±2.51)%, P<0.001], and apoptosis rate was significantly reduced [(6.83±0.27)% vs (10.24±0.76)%, P<0.001; (6.68±0.38)% vs (10.24±0.76)%, P<0.001]. Conclusions: 4G6M-VHH, 5BVP-VHH, and 5MVZ-VHH are expressed by both pET-16b and pHEN1 expression vectors and the nanobodies produced by the pHEN1 vector display enhanced antigen affinity. Furthermore, in hypoxic cardiomyocytes, pHEN1-5MVZ-VHH treatment reduces cell apoptosis.

Stress analysis of self-tightness metal sealing against ultrahigh pressure medium.

Stress is one of the most important factors in metal-to-metal sealing. In this paper, two methods (theoretical and empirical) were adopted to calculate the normal stress of the brass sealing surfaces against different ultrahigh pressure liquid. The theoretical formula was derived in terms of force balance, and the empirical formula was obtained by polynomial curve fitting, which the fitted data were from simulated results; besides, the results calculated using the empirical formula agree well with the results by theoretical formula. Meanwhile, the equivalent stresses of the brass seal, normal stress and contact stress on the brass seal surfaces were simulated by finite element method, and the simulated results indicated these stresses are increased with the increase of liquid pressure, and the maximum stresses always appear on the tip of the brass seal.

[Efficacy of neoadjuvant therapy on HER2-positive breast cancer: a clinicopathological analysis].

Objective: To investigate the efficacy of neoadjuvant therapy (NAT) on HER2-positive breast cancer and to analyze their clinicopathological features. Methods: A total of 480 cases of HER2-positive breast cancer who received neoadjuvant therapy (NAT), diagnosed at the Department of Pathology of Fudan University Shanghai Cancer Center from 2015 to 2020, were retrospectively identified. Clinicopathological parameters such as age, tumor size, molecular subtype, type of targeted therapy, Ki-67 proliferation index, ER and HER2 immunohistochemical expression, and HER2 amplification status were analyzed to correlate with the efficacy of NAT. Results: Among 480 patients with HER2-positive breast cancer, 209 achieved pathology complete response (pCR) after NAT, with a pCR rate of 43.5%. Of all the cases,457 patients received chemotherapy plus trastuzumab and 23 patients received chemotherapy with trastuzumab and pertuzumab. A total of 198 cases (43.3%) achieved pCR in patients with chemotherapy plus trastuzumab, and 11 cases (47.8%) achieved pCR in patients with chemotherapy plus trastuzumab and pertuzumab. The pCR rate in the latter group was higher, but there was no statistical significance. The results showed that the pCR rate of IHC-HER2 3+patients (49%) was significantly higher than that of IHC-HER2 2+patients (26.1%, P<0.001). The higher the mean HER2 copy number in the FISH assay, the higher the pCR rate was achieved. The expression level of ER was inversely correlated with the efficacy of NAT, and the pCR rate in the ER-positive group (28.2%) was significantly lower than that in the ER-negative group (55.8%, P<0.001). The pCR rate (29.1%) of patients with luminal B type was lower than that of HER2 overexpression type (55.8%, P<0.001). In addition, higher Ki-67 proliferation index was associated with higher pCR rate (P<0.001). The pCR rate was the highest in the tumor ≤2 cm group (57.7%), while the pCR rate in the tumor >5 cm group was the lowest (31.1%). The difference between the groups was significant (P=0.005). Conclusions: HER2 copy numbers, HER2 immunohistochemical expression level, molecular subtype, ER expression level and Ki-67 proliferation index are significantly associated with pCR after NAT. In addition, fluorescence in situ hybridization results, HER2/CEP17 ratio and tumor size could also significantly affect the efficacy of NAT.

[Maresin1 inhibits the NF-κB/caspase-3/GSDME signaling pathway to alleviate hepatic ischemia-reperfusion injury].

Objective: To investigate the role of Maresin1 (MaR1) in hepatic ischemia-reperfusion injury (HIRI). Methods: The HIRI model was established and randomly divided into a sham operation group (Sham group), an ischemia-reperfusion group (IR group), and a MaR1 ischemia-reperfusion group (MaR1+IR group). MaR1 80ng was intravenously injected into each mouse's tail veins 0.5h before anesthesia. The left and middle hepatic lobe arteries and portal veins were opened and clamped. The blood supply was restored after 1h of ischemia. After 6h of reperfusion, the mice were sacrificed to collect blood and liver tissue samples. The Sham's group abdominal wall was only opened and closed. RAW267.4 macrophages were administered with MaR1 50ng/ml 0.5h before hypoxia, followed by hypoxia for 8h and reoxygenation for 2h, and were divided into the control group, the hypoxia-reoxygenation group (HR group), the MaR1 hypoxia-reoxygenation group (MaR1 + HR group), the Z-DEVD-FMK hypoxia-reoxygenation group (HR+Z group), the MaR1 + Z-DEVD-FMK hypoxia-reoxygenation group (MaR1 + HR + Z group), and the Con group without any treatment. Cells and the supernatant above them were collected. One-way analysis of variance was used for inter-group comparisons, and the LSD-t test was used for pairwise comparisons. Results: Compared with the Sham group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1ß, and IL-18 in the IR group were significantly higher (P < 0.05), with remarkable pathological changes, while the level in the MaR1 + IR group was lower than before (P < 0.05), and the pathological changes were alleviated. Compared with the Con group, the HR group had higher levels of IL-1ß and IL-18 (P < 0.05), while the MaR1 + HR group had lower levels of IL-1ß and IL-18 (P < 0.05). Western blot showed that the expressions of caspase-3, GSDME, and GSDME-N were significantly higher in the HR group and IR group than in the other groups; however, the expression was lower following MaR1 pretreatment. The Z-DEVD-FMK exploration mechanism was inhibited by the expression of caspase-3 in HIRI when using MaR1. Compared with the HR group, the IL-1ß and IL-18 levels and the expressions of caspase-3, GSDME, and GSDME-N in the HR + Z group were decreased (P < 0.05), while the expression of nuclear factor κB was increased, but following MaR1 pretreatment, nuclear factor κB was decreased. There was no significant difference in the results between the MaR1 + H/R group and the MaR1 + H/R + Z group (P > 0.05). Conclusion: MaR1 alleviates HIRI by inhibiting NF-κB activation and caspase-3/GSDME-mediated inflammatory responses.

[A study of the clinical curative effect of nucleos(t)ide analogues treated to pegylated interferon-α add-on therapy in patients with chronic hepatitis B].

Objective: To investigate the hepatitis B surface antigen (HBsAg) clearance condition and its predictive factors after treatment with nucleos(t)ide analogues to pegylated interferon-α add-on therapy in patients with chronic hepatitis B. Methods: Patients with chronic hepatitis B who visited the First Affiliated Hospital of Zhengzhou University from 2018~2019 were prospectively enrolled. HBsAg≤ 1500 IU/mL, hepatitis B e antigen-negative, HBV DNA undetectable, received antiviral treatment with nucleos(t)ide analogues for at least one year, and pegylated interferon-α add-on therapy for 48 weeks were included. The primary endpoint of study was to determine the proportion of HBsAg clearance at 72 weeks. Concurrently, the predictive factors for HBsAg clearance were analyzed. Quantitative and qualitative data were analyzed using a t-test or non-parametric test and a Fisher's exact test. Results: A total of 38 cases were included in this study, of which 13 cases obtained HBsAg clearance at 48 weeks of therapy and another six cases obtained HBsAg clearance throughout the extended treatment period of 72 weeks, accounting for 50.00% of all enrolled patients. There was a significant difference in HBsAg dynamics between the HBsAg clearance group and the non-clearance group (P < 0.05). Univariate logistic regression analysis showed that patients' age, baseline, 12-and 24-week HBsAg levels, and early HBsAg reduction were predictive factors for HBsAg clearance at 72 weeks of treatment. Multivariate logistic regression analysis showed that age (OR = 1.311; P = 0.016; 95% confidence interval: 1.051~1.635) and HBsAg levels at 24 weeks of treatment (OR = 4.481; P = 0.004; 95% confidence interval: 1.634~12.290) were independent predictors for HBsAg clearance. Conclusion: Hepatitis B e antigen-negative, nucleos(t)ide analogue treated, HBsAg ≤ 1500 IU/mL, and HBV DNA undetectable, peg-IFNα add-on treatment for 48 weeks could promote HBsAg clearance in patients with chronic hepatitis B. Six of the sixteen cases (37.50%) who did not obtain HBsAg clearance at week 48 did so with the course of therapy extended to week 72. Hence, the optimal individualized treatment strategy should be customized according to the predictors rather than the fixed 48-week course. Age (≤ 38), baseline HBsAg level (≤2.86 log(10)IU/ml), HBsAg level at 24 weeks (≤ 0.92 log(10)IU/ml), and 12-week HBsAg decrease from baseline (≥ 0.67 log(10)IU/ml) indicate that patients are highly likely to obtain HBsAg clearance at the 72 weeks of combination therapy, in which the combined indicator based on HBsAg level ≤0.92 log(10)IU/ml at 24 weeks will identify 85.0% to 100.0% of patients with HBsAg clearance.

[Clinical features and long-term prognosis of diabetic patients with low or intermediate complexity coronary artery disease post percutaneous coronary intervention].

Objective: To investigate the clinical features and long-term prognostic factors of diabetic patients with low or intermediate complexity coronary artery disease (CAD) post percutaneous coronary intervention (PCI). Methods: This was a prospective, single-centre observational study. Consecutive diabetic patients with SYNTAX score (SS)≤32 undergoing PCI between January and December 2013 in Fuwai hospital were included in this analysis. The patients were divided into two groups based on SS, namely SS≤22 group and SS 23-32 group. Multivariate Cox regression analysis was performed to identify independent factors related to poor 5-year prognosis. The primary outcomes were cardiac death and recurrent myocardial infarction, the secondary outcomes were all cause death and revascularization. Results: Of the 3 899 patients included in the study, 2 888 were men (74.1%); mean age was 59.4±9.8 years. There were 3 450 patients in the SS≤22 group and 449 patients in the SS 23-32 group. Compared with SS≤22 group, the incidence of revascularization was higher in SS 23-32 group (18.9% (85/449) vs. 15.2% (524/3450), log-rank P=0.019). There was no significant difference in all-cause death, cardiac death and recurrent myocardial infarction between the two groups (log-rank P>0.05). Multivariate Cox regression analysis showed that age (HR=1.05, 95%CI 1.02-1.08, P<0.001), chronic obstructive pulmonary disease (HR=3.12, 95%CI 1.37-7.07, P=0.007) and creatinine clearance rate (CCr)<60 ml/min (HR=3.67, 95%CI 2.05-6.58, P<0.001) were independent risk factors for 5-year cardiac death, while left ventricular ejection fraction (HR=0.94, 95%CI 0.91-0.96, P<0.001) was a protective factor. Previous PCI (HR=2.04, 95%CI 1.38-3.00, P<0.001), blood glucose level≥11.1 mmol/L on admission (HR=2.49, 95%CI 1.32-4.70, P=0.005) and CCr<60 ml/min (HR=1.85, 95%CI 1.14-2.99, P=0.012) were independent risk factors for 5-year recurrent myocardial infarction. The SS of 23-32 was independently associated with risk of revascularization (HR=1.54, 95%CI 1.09-2.16, P=0.014), after adjusting for residual SS. Residual SS was not a risk factor for 5-year prognosis. Conclusions: In diabetic patients with low-or intermediate complexity CAD, SS 23-32 is associated with increased risk of 5-year revascularization; the clinical characteristics of the patients are associated with the long-term mortality and recurrent myocardial infarction, but not related to revascularization.

[A case report of death from toxic encephalopathy caused by emamectin·chlorfenapyr].

Emamectin·chlorfenapyr is insecticide compounded by emamectin benzoate and chlorfenapyr. There is no special antidote after poisoning, and the mortality rate of patients is very high. We admitted a case of toxic encephalopathy caused by oral administration of emamectin·chlorfenapyr. The clinical manifestations of patient were gastrointestinal symptoms, profuse sweating, high fever, changes in consciousness. After admitted to the hospital, despite active comprehensive treatment, the patient died of ineffective rescue eventually.

Association of aldehyde exposure with bone mineral density in the national health and nutrition examination survey (NHANES 2013-2014).

PURPOSE: The association between aldehyde exposure and bone health in humans remains unclear. This study was to evaluate the association of serum aldehydes with bone mineral density (BMD) and osteopenia/osteoporosis. METHODS: We analyzed the US National Health and Nutrition Examination Survey cross-sectional data from 2013 to 2014. Weighted multivariate-adjusted linear regression and logistic regression models were used to assess the association between specific aldehydes and osteopenia/osteoporosis. Associations between aldehyde combinations and BMD were also evaluated using the restricted cubic spline (RCS) method. RESULTS: Compared with men in the first tertile, those in the third tertile of propanaldehyde concentration were negatively associated with proximal femur and lumbar spine BMD. Significant inverse associations were observed between benzaldehyde exposure and trochanter BMD in women. Benzaldehyde increased the risk of osteopenia/osteoporosis 2.75-fold [95% confidence interval (CI) = 1.06, 7.11] in the highest tertile in women compared to the lowest tertile concentration. In males, the prevalence of total femur, femur neck, and trochanter osteopenia/osteoporosis was significantly higher in the highest versus the lowest tertile of propanaldehyde exposure, with odds ratios (ORs) of 6.84 (95% CI = 2.33, 20.04), 2.72 (95% CI = 1.18, 6.27), and 3.26 (95% CI = 1.25, 8.56), respectively. RCS regression also showed decreased BMD continuously with increasing serum mixed aldehyde levels. CONCLUSIONS: Serum aldehyde concentrations were associated with low BMD and high osteopenia/osteoporosis risk in adults, with propanaldehyde and benzaldehyde being the most critical. Co-exposure to aldehyde combinations was negatively correlated with BMD.

[Respiratory drive in acute respiratory distress syndrome: evaluation and control].

Acute respiratory distress syndrome (ARDS) is a common critical disease, which often leads to poor prognosis in critically ill patients. The excessive respiratory drive in ARDS is related to lung injury. Control of excessive respiratory drive is helpful to reduce lung injury and mortality of ARDS. The mechanisms of abnormal increase in respiratory drive in ARDS include hypoxemia, hypercapnia, stretch reflex caused by alveolar collapse and inflammatory stimulation. Respiratory drive should be evaluated by clinical manifestations, physiological parameters and respiratory mechanics indexes. It is particularly important to make individual therapy strategies according to the evaluation of respiratory drive. Analgesia and sedation combined with muscle relaxation, high positive end-expiratory pressure (PEEP) and prone position can be used to control excess respiratory drive. This article reviews the evaluation and management of excess respiratory drive in ARDS patients.

[Evaluation of severity and prognosis of acute pancreatitis by CT severity index and modified CT severity index].

Objectives: To explore the role of computed tomography (CT) severity index (CTSI) and modified CT severity index (MCTSI) in assessing the severity of acute pancreatitis (AP) under the revised Atlanta classification (RAC) and predicting the clinical prognosis. Methods: Based on the prospectively entered AP database, the clinical data of consecutive adult AP inpatients admitted to the Department of Gastroenterology of the First Affiliated Hospital of Nanchang University from January 2012 to December 2020 were retrospectively screened. The imaging data were independently evaluated by two radiologists and entered to the database to calculate the CTSI and MCTSI scores. Their relationship with the difference of RAC severity grade and clinical prognosis was analyzed. Compared with Acute Physiology and Chronic Health Assessment Ⅱ (APACHE Ⅱ) score, the receiver operating characteristic curve was used to evaluate the predictive value of CTSI and MCTSI scores for persistent organ failure and infectious pancreatic necrosis (IPN). Results: A total of 2 612 patients with AP, aged (50±15) years, were included in the study, including 1 547 males (59.2%) and 1 065 females (40.8%). According to RAC standard, AP was divided into 699 cases (26.8%) of mild pancreatitis (MAP), 1 098 cases (42.0%) of moderately severe pancreatitis (MSAP), and 815 cases (31.2%) of severe pancreatitis (SAP). MCTSI judged AP severity similarly to RAC, with 668 cases of MAP (25.6%), 1 207 cases of MSAP (46.2%) and 737 cases of SAP (28.2%), while CTSI judged SAP patients less(400 cases, 15.3%). The severity of AP determined by CTSI and MCTSI scores was significantly correlated with clinical prognosis (r=0.06-0.43, all P<0.05). Compared with APACHE Ⅱ score, CTSI had the highest area under the curve (AUC) for predicting IPN (AUC=0.85, 95%CI: 0.83-0.87), followed by MCTSI (AUC=0.82, 95%CI: 0.80-0.85). APACHE Ⅱ was more accurate in predicting persistent organ failure than CTSI and MCTSI scores,with AUC of 0.73 (95%CI: 0.71-0.75), 0.72 (95%CI: 0.70-0.74) and 0.72 (95%CI: 0.70-0.74), respectively. Conclusions: AP severity judged by MCTSI is consistent with RAC, and SAP patients judged by CTSI are less than RAC. CTSI and MCTSI are significantly correlated with clinical prognosis. CTSI and MCTSI have higher accuracy in predicting IPN, but lower accuracy in predicting persistent organ failure than APACHE Ⅱ.

[SMARCA4-deficient undifferentiated carcinoma of the gastrointestinal tract: a clinicopathological and immunohistochemical study of nine cases].

Objective: To investigate the clinicopathological features, immunophenotype and differential diagnoses of SMARCA4-deificient undifferentiated carcinoma (SMARCA4-DUC) of the gastrointestinal tract. Methods: The clinicopathological data and immunohistochemical profiles of nine cases of SMARCA4-DUC of the gastrointestinal tract diagnosed in Fudan University Shanghai Cancer Center, from 2018 to 2021, were analyzed retrospectively. The relevant literature was reviewed. Results: There were seven males and two females with age at presentation ranging from 39 to 74 years (mean 58 years, median 64 years). The tumor occurred in the stomach (6 cases), right hemicolon (2 cases) and duodenum (1 case). The main symptoms included dysphagia, abdominal pain, diarrhea and melena. Five cases were resected, and the tumor sizes ranged from 5.0 to 8.7 cm (mean 6.7 cm). Microscopically, the tumor was composed of sheets of undifferentiated round to epithelioid cells with large vesicular nuclei harboring prominent nucleoli and displaying brisk mitotic activity. Foci of dyscohesive rhabdoid cells were also noted. The tumor cells were generally uniform; however, prominent pleomorphism and spindle cell component was present in one case each. Five cases contained areas of coagulative necrosis, and one case showed myxoid change of the stroma. By immunohistochemistry, eight cases showed complete loss of BRG1 (SMARCA4) and BRM (SMARCA2) expression. Whereas the expression of these two markers was lost in the epithelioid component of one case, it remained in the spindle cell component (mosaic pattern). Apart from one case with partial expression of pan-cytokeratin, all other eight cases showed either limited (<5%, n=5) or totally negative (n=3) staining of pan-cytokeratin. In addition, four cases also expressed CD34, SOX2 and SALL4. Six patients had follow-up data: four died of disease within 1 year. Conclusions: SMARCA4-DUC of the gastrointestinal tract represents a highly aggressive malignancy with poor outcome. Due to lack of cell-specific differentiation, it is not uncommonly misdiagnosed as a wide variety of poorly-differentiated or undifferentiated tumors. Increased recognition of this rare but distinctive entity not only facilitates the diagnosis and differential diagnosis, but also provides important therapeutic and prognostic information for the clinicians.

[Impact of prolonging dual antiplatelet therapy on long-term prognosis of elderly patients with coronary heart disease complicated with diabetes mellitus undergoing drug-eluting stent implantation].

Objective: To explore and compare the effect of standard or prolonged dual antiplatelet therapy (DAPT) on the long-term prognosis of elderly patients with coronary heart disease complicated with diabetes mellitus after drug-eluting stent (DES) implantation. Methods: Consecutive patients with diabetes mellitus, ≥65 years old, underwent DES implantation, and had no adverse events within 1 year after operation underwent percutaneous coronary intervention (PCI) from January to December 2013 in Fuwai Hospital were enrolled in this prospective cohort study. These patients were divided into three groups according to DAPT duration: standard DAPT duration group (11 ≤ DAPT duration≤ 13 months) and prolonged DAPT duration group (1324 months). All the patients were followed up at 1, 6 months, 1, 2 and 5 years in order to collect the incidence of major adverse cardiovascular and cerebrovascular events (MACCE), and type 2 to 5 bleeding events defined by the Federation of Bleeding Academic Research (BARC). MACCE were consisted of all cause death, myocardial infarction, target vessel revascularization or stroke. The incidence of clinical adverse events were compared among 3 different DAPT duration groups, and Cox regression model were used to analyze the effect of different DAPT duration on 5-year long-term prognosis. Results: A total of 1 562 patients were enrolled, aged (70.8±4.5) years, with 398 female (25.5%). There were 467 cases in standard DAPT duration group, 684 cases in 1324 months group. The patients in standard DAPT duration group and the prolonged DAPT duration groups accounted for 29.9% (467/1 562) and 70.1% (1 095/1 562), respectively. The 5-year follow-up results showed that the incidence of all-cause death in 1324 month group(4.1%(17/411) vs. 8.6%(40/467),P=0.008) were significantly lower than in standard DAPT group. The incidence of myocardial infarction in 1324 month group were 19.3% (90/467), 12.3% (84/684), 20.2% (83/411), respectively, P<0.001). There was no significant difference in the incidence of stroke and bleeding events among the three groups (all P>0.05). Multivariate Cox analysis showed that compared with the standard DAPT group, prolonged DAPT to 13-24 months was negatively correlated with MACCE (HR=0.601, 95%CI 0.446-0.811, P=0.001), all-cause death (HR=0.568, 95%CI 0.357-0.903, P=0.017) and myocardial infarction (HR=0.353, 95%CI 0.179-0.695, P=0.003). DAPT>24 months was negatively correlated with all-cause death (HR=0.687, 95%CI 0.516-0.913, P=0.010) and positively correlated with revascularization (HR=1.404, 95%CI 1.116-1.765, P=0.004). There was no correlation between prolonged DAPT and bleeding events. Conclusions: For elderly patients with coronary heart disease complicated with diabetes mellitus underwent DES implantation, and had no MACCE and bleeding events within 1 year after operation, appropriately prolonging of the DAPT duration is related to the reduction of the risk of cardiovascular adverse events. Patients may benefit the most from the DAPT between 13 to 24 months. In addition, prolonging DAPT duration does not increase the incidence of bleeding events in this patient cohort.

Gene polymorphisms of pro-inflammatory cytokines may affect the risk of Graves' disease: a meta-analysis.

PURPOSE: Gene polymorphisms of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) may influence the risk of Graves' disease, but the results of so far published studies remain inconclusive. Therefore, the authors conducted this meta-analysis to assess relationships between TNF-α/IL-1/IL-6 polymorphisms and the risk of Graves' disease by pooling the findings of all relevant studies. METHODS: A comprehensive literature searching of Pubmed, Embase, Web of Science and CNKI was conducted by the authors, and twenty-eight studies were found to be eligible for pooled analyses. RESULTS: The pooled meta-analyses results showed that genotypic frequencies of TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects differed significantly. Moreover, we found that genotypic frequencies of TNF-α rs1800629 and IL-6 rs1800795 polymorphisms among patients with Graves' disease and control subjects in Caucasians differed significantly, and genotypic frequencies of IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects in Asians also differed significantly. Nevertheless, we did not detect such genotypic frequencies differences for TNF-α rs361525 and IL-1B rs1143627 polymorphisms. CONCLUSIONS: This meta-analysis suggests that TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves' disease in overall population. Moreover, TNF-α rs1800629 and IL-6 rs1800795 polymorphisms may influence the risk of Graves' disease in Caucasians, while IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves' disease in Asians.

Changes of the intestinal microbiota along the gut of Japanese Eel (Anguilla japonica).

Fish intestine contains different types of microbiomes, and bacteria are the dominant microbiota in fishes. Studies have identified various core gut bacteria in fishes. However, little is known about the composition and their relative functions of gut microbial community along the intestine. To explore this, the current study investigated the microbial community distribution along the gut in Anguilla japonica. By 16S rRNA gene sequencing, we profiled the gut microbiota in eel along the three regions (anterior intestine (AI), the middle intestine (MI) and the posterior intestine (PI)). Results suggested that the three regions did not have significant differences on the observed species and diversities. The cluster tree analysis showed that the bacteria community in MI was closer to PI than the AI. The dominant bacteria in AI were the Proteobacteria, in which the majority was graduated replaced by Bacteroidetes along the gut to PI region. Through PICRUSt analysis, shifts in the bacterial community along the gut were found to affect the genetic information processing pathways. Higher levels of translation and transcriptional pathway activities were found in MI and PI than in AI. The dominant bacterial species were different among the regions and contributed to various biological functions along the gut.

JAB1 Promotes High Glucose-Induced Inflammation and Extracellular Matrix Deposition in Glomerular Mesangial Cells by Regulating Angiopoietin-Like Protein 2.

Diabetic or hyperglycaemic conditions stimulate the inflammatory response, excessive accumulation of extracellular matrix, and result in glomerulosclerosis, a scarring process of diabetic nephropathy. c-Jun activation domain-binding protein 1 (JAB1) functions as a regulator of pathways involved in cellular apoptosis and proliferation. The role of JAB1 in diabetic nephropathy was investigated in this study. Firstly, glomerular mesangial cells (GMCs) were treated with high glucose, and high glucose conditions induced up-regulation of JAB1 in the GMCs. Moreover, IL-6, TNF-α, MCP-1, and IL-1ß were also elevated in high glucose-induced GMCs. Secondly, silencing of JAB1 reduced the levels of IL-6, TNF-α, MCP-1, and IL-1ß in high glucose-induced GMCs. In addition, silencing of JAB1 attenuated the high glucose-induced decrease of superoxide dismutase (SOD) and the increase of reactive oxygen species (ROS) and malondialdehyde (MDA). The increased TGF-ß1, collagen I, collagen IV, and fibronectin levels in high glucose-induced GMCs were restored by knockdown of JAB1. Thirdly, angiopoietin-like protein 2 (ANGPTL2) expression was reduced by JAB1. Over-expression of ANGPTL2 weakened the JAB1 silence-induced decrease of IL-6, TNF-α, MCP-1, IL-1ß, TGF-ß1, collagen I, collagen IV, and fibronectin. In conclusion, silencing of JAB1 reduced extracellular matrix deposition and suppressed inflammation in high glucose-induced GMCs through down-regulation of ANGPTL2.

Preventive intraperitoneal hyperthermic perfusion chemotherapy for patients with T4 stage colon adenocarcinoma.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be an effective treatment for peritoneal tumors; whether preventive HIPEC after radical resection for T4 stage colon adenocarcinoma could decrease peritoneal recurrence remains unknown. The aim of the present study was to compare peritoneal recurrence and short-term survival in patients with T4 stage colon adenocarcinoma undergoing HIPEC plus adjuvant chemotherapy or adjuvant chemotherapy alone following surgery. METHODS: We retrospectively reviewed T4 stage colon adenocarcinoma patients who had radical tumor resection at our institution between January 2014 and January 2019. Clinical data were extracted from the database at our institution, and patient survival and long-term complications were assessed through repeated outpatient examinations and telephone interviews. RESULTS: A total of 352 patients were included in this study; 157 patients received postoperative HIPEC plus adjuvant chemotherapy (HIPEC group), 195 patients received adjuvant chemotherapy alone (conventional chemotherapy group). Forty-one (26.1%) patients in the HIPEC group had a peritoneal recurrence and the peritoneum was the first site of tumor recurrence in 6 (14.6%) of them. However, 73 (37.4%) patients experienced peritoneal recurrence in the conventional group, and the peritoneum was the first site of tumor recurrence in 25 (34.2%) (p = 0.019). Disease-free survival in the HIPEC group at 1 and 3 years was 93.3% and 61.1%, respectively, versus 89.3% and 51.7% in the conventional chemotherapy group (p = 0.038). Overall survival in the HIPEC group at 1 and 3 years was 100.0% and 82.7%, respectively, versus 100.0% and 76.9% in the conventional chemotherapy group (p = 0.420). The two groups did not differ with respect to severe complications. CONCLUSIONS: Preventive HIPEC after radical surgery may decrease peritoneal recurrence and promote disease-free survival for T4 stage colon adenocarcinoma. Large-scale randomized controlled studies are needed to confirm the results of our study.

[Effect of long non-coding RNA MBNL1-AS1 expression on prognosis of acute myeloid leukemia patients].

Objective: To explore the prognosis effect of the expression of long-chain non-coding RNA (lncRNA) MBNL1-AS1 on acute myeloid leukemia (AML) patients. Methods: One hundred and twenty-five AML patients of the Cancer Genome Atlas (TCGA) from November 2001 to March 2010 were involved, including 70 patients who received chemotherapy only and other 55 patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in addition to chemotherapy. According to the median expression of lncRNA MBNL1-AS1, patients of chemotherapy group were divided into high expression sub-group(n=35) and low expression sub-group (n=35), and patients of allo-HSCT group were also divided into high expression sub-group (n=28) and low expression sub-group (n=27) for prognosis analysis. Clinical characteristics at diagnosis, including peripheral white blood cell counts (WBC), blast percentages in peripheral blood and bone marrow (BM), French-American-British (FAB) subtypes and the frequencies of common genetic mutations in AML were described. The event-free survival (EFS) rate and overall survival (OS) rate of patients in different groups were analyzed, and the influence of the clinical characteristics of patients on the prognosis of AML was analyzed by COX multivariate analysis. Results: In the chemotherapy group, patients with low lncRNA-MBNL1-AS1 expression had significantly lower EFS and OS (60.0%, 8.6%) than patients with high lncRNA-MBNL1-AS1 expression (68.6%, 34.3%) (χ²=7.817, 10.880, all P<0.01). However, in the alloHSCT group, no significant differences were observed in EFS and OS of patients between high and low expression groups of lncRNA-MBNL1-AS1 (all P>0.05). COX multivariate analysis confirmed that age≥60 years old (EFS: HR (95%CI): 6.934 (1.918-25.075),P=0.003;OS: HR (95%CI): 4.119 (1.812-9.364), P=0.001), and low expression of lncRNA MBNL1-AS1 (EFS: HR (95%CI): 0.354 (0.126-0.941), P=0.038; OS: HR (95%CI): 0.424 (0.231-0.778), P=0.006)were independent risk factors for EFS and OS in the chemotherapy group. Conclusion: The long-chain non-coding RNA MBNL1-AS1 is related to the prognosis of AML, and its low expression is an independent poor prognostic factor in AML patients.

[A birth cohort study on the effect of chronotype during pregnancy on small for gestational age and the mediating effect of glucose-lipid metabolism].

Objective: To explore the relationship between maternal sleep time and the risk of small for gestational age (SGA), and to evaluate the role of glucose-lipid metabolism in the association. Methods: A total of 6 821 women who was second pregnancy were recruited from pregnancies consulted at Hefei First People's Hospital, Anhui Province Maternity & Child Health Hospital and the First Affiliated Hospital of Anhui Medical University from March 2015 to April 2019, and a face-to-face questionnaire survey was conducted to collect general demographic characteristics, dietary habits and routine lifestyles. Sleep information including bedtime, getup and sleep duration were reported by pregnant woman herself, and this survey as well as the third trimester of gestation. Pregnancy and birth outcomes were collected at delivery. A total of 5 488 mother-pairs with complete data were obtained in the final data. The non-linear relationship between chronotype and SGA risk was explored by restricted cubic spline regression model, and the role of glucose-lipid metabolism in the association between sleep midpoint and SGA was explored by using the mediating model based on bootstrap method. Results: The incidence of SGA was 8.4% (459/5 488) in eligible pregnant women. Compared with the pregnant women who went to bed before 21∶00, the risk of SGA of women who went to bed after 23∶00 am (OR=1.54, 95%CI: 1.01-2.34) was significantly higher in the multivariate logistic regression model. Additionally, the risk of SGA in pregnant women who got up after 8∶00 am was significantly higher than those women who got up before 8 o'clock (OR=1.31, 95%CI:1.05-1.62). However, the significant association between sleep duration and SGA was not found. In the restricted cubic spline regression, the risk of SGA was significantly increased from the specific midpoint of 02∶45 am (P<0.05). Moreover, mediation model showed that the negative effect of late sleep in the second trimester on SGA may be partially explained through glucose-lipid metabolism(all P<0.05). Conclusion: Maternal sleep status at the second trimester of gestation may be more susceptible to SGA. Lately sleep midpoint may be a potential independent risk factor for increased risk of SGA, and furtherly affect the occurrence of SGA by changing the level of glucose and lipid metabolism.

[A cohort study of maternal pregnancy-related anxiety at different trimesters and infants' neurobehavioral development].

Objective: To investigate the influence and critical period of pregnancy-related anxiety during pregnancy on the neurobehavioral development of infants. Methods: The subjects of this study were derived from the Ma'anshan Birth Corhot. From May 2013 to September 2014, a total of 3 474 pregnant women who registered in Ma 'anshan Maternal and Child Health Care Center were enrolled in the study. A total of 2 242 mother-infant pairs who completed three times assessments of maternal anxiety and at least once assessment of infants' neurobehavioral development were included in the final analysis. Maternal pregnancy-related anxiety was assessed by the Pregnancy-Related Anxiety Questionnaire during the first, second and third trimesters of pregnancy. When their children were at 6 and 18 months, their neurobehavioral development was evaluated using the Ages & Stages Questionnaire-China. The influence of maternal pregnancy-related anxiety on the neurobehavioral development of infants was analyzed by bi-nominal logistic regression. Results: The age of 2 242 pregnant women was (26.62±3.65) years, and the proportion of boys, low birth weight and exclusive breastfeeding for 6 months was 50% (1 120/2 242), 1.7% (38/2 242) and 11.5% (252/2 191), respectively. The detection rates of pregnancy-related anxiety during the first, second and third trimester were 24.9% (558), 28.6% (642) and 30.3% (674), respectively. After controlling confounding variables and other two trimester's anxiety, only pregnancy-related anxiety during the third trimester (not first or second trimester) significantly increased the risk of developmental delay in the domain of communication (relative risk, RR = 3.52, 95% confidence interval, CI: 1.89-6.58) and personal-social (RR=2.46, 95%CI: 1.10-5.49) at the 6 months of age, as well as in the domain of fine motor (RR=2.07, 95%CI: 1.11-3.85), problem-solving domains (RR=2.31, 95%CI: 1.24-4.31). Conclusion: Maternal pregnancy-related anxiety was associated with the risk of neurobehavioral development of infants, and the third trimester may be the critical period.

[Evaluation of infrahepatic inferior vena cava clamping in robot-assisted laparoscopic liver resection].

Objective: To evalutate the safety and efficacy of infrahepatic inferior vena cava clamping robot-assisted laparoscopic liver resection. Methods: All data about 24 patients with robotic liver resection at Hepatic Surgery Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology between February 2015 and December 2017 were collected and analyzed. These patients were divided into two groups based on different methods to decrease central venous pressure. Eight patients(6 males and 2 females,aged 49 years(range:50 to 56 years)) were applied with infrahepatic inferior vena cava clamping,and the other 16 matched cases (15 males and 1 female,aged 53 years(range:38 to 69 years)) were categorized into lowering central venous pressure group. Intraoperative blood loss,blood transfusion,intraoperative hemodynamic parameters,postoperative complications,and renal function were compared by t-test,non-parametric test,χ2 test,or Fisher exact test. Results: There was significantly difference in the intraoperative blood loss between the infrahepatic vena cava clamping group and the lowering central venous group(200(220) ml (range:100 to 400 ml) vs. 750(800) ml (range:100 to 2 000 ml),Z=‒2.169,P=0.030). The clamping time of portal triad and infrahepatic inferior vena cava were 24 (18) minutes and 29 (20) minutes in the infrahepatic inferior vena cava clamping group, and portal triad clamping time was 23 (23) minutes in the low central venous group. There was no significant difference between the two groups (Z=‒0.323, P=0.747). There was no intraoperative blood transfusion in the infrahepatic inferior vena cava clamping group, and 5 cases in the low central venous group, with a transfusion volume of 1.5(1.5)U. The difference between the two groups was statistically significant (Z=‒3.353, P=0.001). However, the mean arterial pressure in the infrahepatic vena cava clamping group decreased from (88.6±4.9) mmHg to (67.4±3.8) mmHg(1 mmHg=0.133 kPa), which was lower than that of lowering central venous group (72.4±3.3) mmHg (t=2.315,P=0.003). And there were no significant differences related to postoperative complications rate or hepatic and renal function in both groups. Conclusion: The infrahepatic inferior vena cava technology is safe and feasible to decrease central venous pressure during robotic liver resections,which will not affect the recovery of hepatic and renal functions.