Objective:To assess the predictive value for the risk of cardiogenic stroke (CS) in patients with paroxysmal atrial fibrillation (PAF) using quantification of left atrial appendage early blood stasis (LAA-BS) signs derived from left atrium-pulmonary vein CT examination.Methods:A retrospective analysis of 187 patients with PAF, who were confirmed to have LAA-BS by left atrium-pulmonary vein CT examinations, was conducted at Second Affiliated Hospital of Nantong University from January 2019 to December 2021. The ratio of LAA-BS CT values to ascending aorta (AA) CT values (HU BS/HU AA) and the ratio of LAA-BS volume to LAA volume (V BS/V LAA) were measured at the peak time of AA enhancement, which were used as characteristic quantitative indicators of LAA-BS. Using the median values of HU BS/HU AA and V BS/V LAA as cut-off points for grouping, the differences between the high-ratio and low-ratio groups were compared in terms of general information, clinical characteristics, and imaging characteristics. All enrolled patients were followed up with the primary outcome event of CS occurrence. The differences in the proportion of CS occurrence between the high-ratio and low-ratio groups were compared. The risk stratification analysis of the occurrence of CS in PAF patients was performed using Kaplan-Meier curves. Additionally, the predictive value of HU BS/HU AA, V BS/V LAA and other imaging indices for the risk of CS occurrence was assessed using Cox proportional risk regression models. Results:The incidence of hypertension and the proportion of patients with atrial fibrillation-stroke risk score (CHA 2DS 2-VASc)≥3 in the high V BS/V LAA group were higher than that in the low V BS/V LAA group, and the difference was statistically significant ( P=0.041, P=0.011). The left atrial volume (LAV) in patients in the low HU BS/HU AA group was greater than in the high HU BS/HU AA group, and the difference was statistically significant ( P=0.040). Kaplan-Meier analysis showed a higher incidence of CS in the low HU BS/HU AA group than in the high HU BS/HU AA group ( P=0.012). Similarly, the high V BS/V LAA group had a higher incidence of CS compared with the low V BS/V LAA group ( P=0.019). Subgroup analysis revealed a significantly higher incidence of CS in the subgroup with low HU BS/HU AA and high V BS/V LAA compared to other subgroups (all P<0.05). The Cox proportional hazards regression model, adjusting for confounding factors, identified low HU BS/HU AA and high V BS/V LAA as independent risk factors for CS occurrence in PAF patients ( P=0.005 and P=0.029). Conclusion:The HU BS/HU AA and V BS/V LAA quantified using left atrium-pulmonary vein CT imaging are predictive factors for CS occurrence in patients with PAF. These ratios synergistically contribute to the risk assessment of CS.

Objective:To assess the predictive value for the risk of cardiogenic stroke (CS) in patients with paroxysmal atrial fibrillation (PAF) using quantification of left atrial appendage early blood stasis (LAA-BS) signs derived from left atrium-pulmonary vein CT examination.Methods:A retrospective analysis of 187 patients with PAF, who were confirmed to have LAA-BS by left atrium-pulmonary vein CT examinations, was conducted at Second Affiliated Hospital of Nantong University from January 2019 to December 2021. The ratio of LAA-BS CT values to ascending aorta (AA) CT values (HU BS/HU AA) and the ratio of LAA-BS volume to LAA volume (V BS/V LAA) were measured at the peak time of AA enhancement, which were used as characteristic quantitative indicators of LAA-BS. Using the median values of HU BS/HU AA and V BS/V LAA as cut-off points for grouping, the differences between the high-ratio and low-ratio groups were compared in terms of general information, clinical characteristics, and imaging characteristics. All enrolled patients were followed up with the primary outcome event of CS occurrence. The differences in the proportion of CS occurrence between the high-ratio and low-ratio groups were compared. The risk stratification analysis of the occurrence of CS in PAF patients was performed using Kaplan-Meier curves. Additionally, the predictive value of HU BS/HU AA, V BS/V LAA and other imaging indices for the risk of CS occurrence was assessed using Cox proportional risk regression models. Results:The incidence of hypertension and the proportion of patients with atrial fibrillation-stroke risk score (CHA 2DS 2-VASc)≥3 in the high V BS/V LAA group were higher than that in the low V BS/V LAA group, and the difference was statistically significant ( P=0.041, P=0.011). The left atrial volume (LAV) in patients in the low HU BS/HU AA group was greater than in the high HU BS/HU AA group, and the difference was statistically significant ( P=0.040). Kaplan-Meier analysis showed a higher incidence of CS in the low HU BS/HU AA group than in the high HU BS/HU AA group ( P=0.012). Similarly, the high V BS/V LAA group had a higher incidence of CS compared with the low V BS/V LAA group ( P=0.019). Subgroup analysis revealed a significantly higher incidence of CS in the subgroup with low HU BS/HU AA and high V BS/V LAA compared to other subgroups (all P<0.05). The Cox proportional hazards regression model, adjusting for confounding factors, identified low HU BS/HU AA and high V BS/V LAA as independent risk factors for CS occurrence in PAF patients ( P=0.005 and P=0.029). Conclusion:The HU BS/HU AA and V BS/V LAA quantified using left atrium-pulmonary vein CT imaging are predictive factors for CS occurrence in patients with PAF. These ratios synergistically contribute to the risk assessment of CS.

Objective:To investigate the current research status, research development trends and hotspots from 2012 to 2022 at home and abroad.Methods:This study collected medical English research articles published in core journals at home and abroad in the past 11 years. Changes in the number of published articles over the years and high-yield journal publications at home and abroad were analyzed using Excel, followed by keyword co-occurrence and cluster analysis using CiteSpace.Results:The number of medical English research articles published in China between years has shown a downward trend, while foreign countries have shown a fluctuating upward trend. Medical English research articles in China were mainly published in medical journals, while those in foreign countries were mainly published in language journals. Research hotspots in medical English at home and abroad covered medical English education, medical discourse, medical vocabulary, medical communication and English academic publication. Both domestic and foreign studies focus on medical English education and medical research articles; as for differences, domestic scholars pay more attention to bilingual teaching mode, English teaching reform and medical vocabulary, while foreign scholars focus more on interlingual and intercultural medical communication and English academic publications by second-language medical scholars.Conclusions:There are certain differences in development trends, high-yield journals, and research hotspots of medical English research at home and abroad in the past 11 years.

Objective:To study the impact of additional resection of an intraoperative proximal bile duct positive margin on the survival rate of patients with hilar cholangiocarcinoma (HCCA).Methods:The clinical data of 214 patients with HCCA treated at the First Affiliated Hospital of Zhengzhou University from January 2000 to January 2017 were analyzed. There were 126 males and 88 females, aged (62.3±17.1) years. These patients were divided into three groups according to the pathological status of bile duct margins and whether the proximal bile duct was further resected. Group A consisted of patients with negative margins without additional resection (161 cases). Group B consisted of patients with negative margins after additional resection (21 cases). Group C consisted of patients with R 1 resections (32 cases). The Kaplan-Meier method was used for survival analysis and log-rank test was used for inter-group comparison. Univariate and multivariate Cox regression analysis were used to analyze prognostic factors. Results:The 3-year and 5-year survival rates of patients in groups A, B, and C were 37.1%, 28.6%, 0 and 18.5%, 10.7%, 0, respectively. The cumulative survival rates of patients in group A and group B were significantly higher than that in group C (all P<0.05). Multivariate Cox regression analysis showed that R 1 proximal bile duct margin ( HR=3.728, 95% CI: 2.531-4.936), margin width >5 mm ( HR=0.534, 95% CI: 0.224-0.857), and T 3-4 staging ( HR=5.655, 95% CI: 3.174-8.203) were independent influencing factors for overall survival of patients with HCCA after attempted radical surgery. Conclusion:The survival rate of patients with HCCA with a positive proximal bile duct margin was significantly improved by further resecting the bile duct to obtain a negative margin. The R 1 proximal bile duct margin was an independent risk factor for prognosis in patients with HCCA after attempted radical resection.

Caspases are a group of structurally related cysteine proteases present in cytosol. One of their important common points is that the active sites contain cysteine and can specifically break the peptide bonds after the aspartic acid residues. Caspases are broadly divided into two groups based on their functions, including inflammatory Caspases and apoptotic Caspases. Inflammatory Caspases include Caspase-1, Caspase-4, Caspase-5, Caspase-11 and Caspase-12, which play important roles in the process of innate immune defense. Unlike inflammatory Caspases, apoptotic Caspases(2/3/6/7/8/910)initiate and execute an immunologically silent form of programmed cell death known as apoptosis. However, ongoing investigations have uncovered essential functions of Caspase-8 in the regulation of immunity in cells and organisms. Accumulated studies have shown that Caspases play important roles in the occurrence and development of various immunity-related diseases. In order to comprehensively elucidate the relationship between Caspases and innate immunity, and to provide some scientific basis and theoretical reference for the treatment of various diseases, this article reviews the regulation of activity and inflammation mechanism of innate immunity-related Caspase-1/4/5/11/8/12.

Objective To evaluate the clinical manifestations, metal metabolism, imaging characteristics and treatment response in patients with delayed Wilson disease (WD). Methods Patients with untreated WD (40 with delayed onset and 40 with non?delayed onset) were enrolled. Twenty healthy people were included as normal controls. All patients were evaluated with modified Young scale neural symptom scores, grade of Child liver function and mental symptoms rating scale, magnetic resonance imaging (MRI) scan, magnetic sensitive imaging (susceptibility weighted imaging, SWI), metal metabolism. Corrected phase (CP) was measured at SWI. After 2 week treatment, neurologic symptoms, liver function, and metal metabolism were reviewed. Results The total score of neurological symptoms in WD patients with delayed onset was lower than that of non?delayed onset (13.00 ± 6.87 vs. 21.13 ± 5.53, P=0.033). The scores of SCL?90 and HAMA depression scales in patients with delayed onset were lower than those of non?delayed onset. On T2 weighted imaging, areas including substantia nigra and thalamus, the caudate nucleus, globus pallidus, putamen presented high signal rate in patients with delated onset than those with non?delayed (P=0.022, 0.037, 0.022, 0.037, 0.029 respectively). The SWI CP values of cangbai sphere and shell nucleus in patients with delayed onset were lower than those with non?delayed onset. Patients with delayed onset had higher urinary copper than those with non?delayed onset before and after treatment (P=0.040, 0.036). After treatment, the score of abnormal tremor and gait in patients with delayed onset was decreased (P=0.037, 0.044), while as the occurrence of neurological symptoms was increased by 10%, and the liver function level in patients with delayed WD was decreased in 3 cases. Conclusions The brain of WD patients with delayed onset is mainly composed of metal deposits, however the cell damage is not apparent. Clinical symptoms are characterized by significant liver injury, but relatively mild neurological and psychiatric symptoms. Patients with delayed WD have higher urinary copper excretion than those with non?delayed WD. Chelating agents improves the neurological symptoms in patients with delayed onset.

Objective To investigate the influence factors of tumor diameter and related prognostic factors on the prognosis of hilar cholangiocarcinoma.Methods The retrospective case-control study was conducted.The clinicopathological data of 240 patients who underwent resection of hilar cholangiocarcinoma in the West China Hospital of Sichuan University between January 1995 and January 2013 were collected,including 104 patients with tumor diameter ≤ 2 cm (8 with tumor diameter ≤ 1 cm and 96 with 1 cm ＜ tumor diameter ≤ 2 cm),85 with 2 cm ＜ tumor diameter ≤ 3 cm and 51 with tumor diameter ＞ 3 cm (40 with 3 cm ＜ tumor diameter ≤ 4 cm and 11 with tumor diameter ＞ 4 cm).Observation indicators:(1) surgical situations;(2) follow-up situations;(3) risk factors analysis affecting the prognosis of patients;(4) correlation analysis between related prognostic indicators and tumor diameter.The follow-up using outpatient examination and telephone interview was performed to detect the survival up to August 2016.The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.The prognostic factors and correlation between related prognostic indicators and tumor diameter were respectively analyzed using the COX proportional hazard model and logistic regression model.Results (1) Surgical situations:240 patients underwent successful resection of hilar cholangiocarcinoma and lymph node dissection.Of 73 patients with postoperative complications,1 died of intraperitoneal infection induced to systemic infection and multiple organ failure,1 diel of renal failure,and other patients were cured by symptomatic treatment.(2) Follow-up situations:240 patients were followed up for 12.0-98.0 months,with a median time of 47.4 months.The overall median survival time,1-,3-and 5-year overall survival rates were respectively 30.6 months,81％,47％ and 29％.The median survival time and 5-year survival rate were 46.5 months,34％ in patients with tumor diameter ≤ 2 cm and 30.5 months,30％ in patients with 2 cm ＜ tumor diameter ≤ 3 cm and 13.8 months,20％ in patients with tumor diameter ＞ 3 cm,respectively,with a statistically significant difference (x2 =17.83,P＜0.05).Results of further analysis showed the median survival time and 5-year survival rate were 31.3 months,38％ in patients with tumor diameter ≤ 1 cm and 46.5 months,34％ in patients with 1 cm ＜ tumor diameter ≤ 2 cm,respectively,with no statistically significant difference (x2=1.16,P＞O.05).The median survival time and 1-year survival rate were 14.7 months,62％ in patients with 3 cm ＜ tumor diameter ≤ 4 cm and 13.0 months,55％ in patients with tumor diameter ＞ 4 cm,respectively,with no statistically significant difference (x2 =2.34,P＞O.05).(3) Risk factors analysis affecting the prognosis of patients:univariate analysis showed that tumor diameter,surgical margin,lymph node metastasis,vascular invasion and histological differentiation were the related factors affecting patients' prognosis [hazard ratio (HR)=1.456,8.714,1.737,2.246,1.665;95％ confidence interval (C I):1.212-1.748,5.558-13.663,1.311-2.301,1.494-3.378,1.375-2.016,P ＜ 0.05].The multivariate analysis showed that 2 cm ＜ tumor diameter ≤ 3 cm,tumor diameter ＞ 3 cm,R1 resection,lymph node metastasis and low-differentiated tumor were the independent risk factors affecting poor prognosis of patients (HR =1.559,1.868,7.410,1.521,2.274,95％ CI:1.125-2.160,1.265-2.759,4.497-12.212,1.136-2.037,1.525-3.390,P＜0.05).(4) Correlation analysis between related prognostic indicators and tumor diameter:the results of univariate analysis showed that there was a correlation between lymph node metastasis,vascular invasion,histological differentiation and T staging of American Joint Committee on Cancer (AJCC) and tumor diameter of 2 cm as a cut-off point (x2 =6.063,4.950,8.770,9.069,P＜0.05).There was a correlation between surgical margin,lymph node metastasis,vascular invasion and histological differentiation and tumor diameter of 3 cm as a cut-off point (x2=10.251,9.919,5.485,15.632,P＜0.05).The results of multivariate analysis showed that lymph node metastasis and T staging of AJCC were independent related factors affecting tumor diameter of 2 cm as a cut-off point[odds ratio (OR) =1.882,2.104,95 ％CI:1.075-3.293,1.220-3.631,P＜0.05];surgical margin and lymph node metastasis were independent related factors affecting tumor diameter of 3 cm as a cut-off point (OR=3.187,2.211,95 ％CI:1.377-7.379,1.133-4.314,P＜0.05).Conclusions The 2 cm ＜ tumor diameter ≤ 3 cm,tumor diameter ＞ 3 cm,R1 resection,lymph node metastasis and low-differentiated tumor are the independent risk factors affecting the prognosis of patients with hilar cholangiocarcinoma.Three cm (T staging in De Oliveira staging system) as the second cut-off point is feasible,meanwhile,2 cm cut-off point may be become another potential tumor dividing point described in De Oliveira staging system.

Aim To investigated the possible effect of COX-2 on the BMP9-induced activation of PI3K/Akt signal in progenitor cells.Methods The activity of alkaline phosphatase(ALP) was measured using histochemical staining or chemiluminescence.The mRNA level of ALP was determined using real-time PCR assay.The protein levels of osteopontin(OPN), osteocalcin(OCN), COX-2, Akt1/2 and phosphorylated Akt1/2 were detected by Western blot.The mRNA level of COX-2 was assayed with RT-PCR, and the mineralization was measured with Alizarin Red staining.Results The ALP activity was apparently increased by BMP9 in C2C12 cells, as well as the protein level of OPN and OCN.The mineralization was also markedly induced by BMP9 in C2C12 cells.BMP9 increased the level of phosphorylated Akt1/2 greatly, although no substantial effect was observed on total protein level of Akt1/2.The BMP9-induced ALP activity was dramatically decreased by the inhibitor of PI3K.The mRNA and protein level of COX-2 were both increased by BMP9 in C2C12cells, and the BMP9-induced ALP activity and mineralization were greatly attenuated by the inhibitor of COX-2.The BMP9-induced phosphorylation level of Akt1/2 was increased by the exogenous expression of COX-2, but decreased by the inhibitor of COX-2.Conclusion Activation of PI3K/Akt signaling may be a critical event in BMP9-induced osteogenic differentiation, and this process may be mediated by the BMP9-upregulated COX-2 in stem cells at least.

Aim To investigate the relationship be-tween the anti-proliferation effect of resveratrol ( Res ) and p38 MAPK in colon cancer cells .Methods Crys-tal violet staining , Western blot and flow cytometry were employed to analyze the effect of Res on the pro-liferation in LoVo cells.Western blot assay was used to detect the effect of Res on the apoptosis of LoVo cells and the phosphorylation of p 38 MAPK.Crystal violet staining and Western blot assay were used to analyze whether p38 MAPK was involved in the Res-induced proliferation inhibition and apoptosis in LoVo cells .Re-sults Res inhibited the proliferation , arrested cell cy-cle at S phase , and increased the protein level of PC-NA in LoVo cells apparently .Res increased the level of Bad in LoVo cells, but decreased the level of Bcl-2. Although Res exerted no substantial effects on total lev-el of p38 MAPK, it markedly increased the phospho-rylation level of p38 MAPK in LoVo cells.p38 MAPK inhibitor promoted the proliferation , and decreased the anti-proliferation effect of Res on LoVo cells .Moreo-ver , the effects of Res on the level of Bcl-2 and Bad were both reduced by the p 38 MAPK inhibitor .Con-clusions Res can inhibit the proliferation of LoVo cells, which may be partly mediated by promoting the phosphorylation of p38 MAPK.

Aim To study the anti-proliferation effect of resveratrol (Res)and the role of Res-induced bone morphorgenetic protein 9 (BMP9 )in this process in colon cancer cells.Methods Crystal violet staining and flow cytomtry were introduced to assay the anti-proliferation effect of Res in LoVo cells.The effect of Res on apoptosis in LoVo cells was also detected with flow cytometry.Then,RT-PCR and Western blot assay were employed to unveil the effect of Res on the ex-pression of BMP9 .The effect of BMP9 on the anti-pro-liferation of Res in LoVo cells was analyzed with crystal violet staining and flow cytometry too.Finally,the effect of Res on the expression of ALK2 and ALK3 was assayed with RT-PCR,and the inhibitor of ALK2 and ALK3 was used to figure out the possible mechanism of BMP9 on Res-induced proliferation inhibition in LoVo cells.Results Res apparently inhibited the prolifera-tion,arrested the cell cycle at S phase in LoVo and in-creased the percentage of apopotic cells in LoVo cells. Res increased the expression of mRNA and protein of BMP9 concentration dependently. Exogenous ex-pressed-BMP9 enhanced the anti-proliferation and ap-optosis inducing effects of Res in LoVo cells, but BMP9 knockdown decreased these effects of Res.Al-though Res had no apparent effect on increasing the phosphorylation of Smad1/5/8,it increased the ex-pression of ALK2 and ALK3 .Inhibition of ALK2 and ALK3 decreased the anti-proliferation effect of Res partly in LoVo cells.Conclusion Res is potent to in-hibit the proliferation of LoVo cells,Which may be mediated by up-regulating the expression of BMP9 and its receptor at least.