[Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase â ¢ clinical trial].

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.

A Potential Strategy for Atherosclerosis Prevention in Modernizing China - Hyperhomocysteinemia, MTHFR C677T Polymorphism and Air Pollution (PM2.5) on Atherogenesis in Chinese Adults.

BACKGROUND: Atherosclerosis is one of the most important global health hazards and air pollution (AP, PM2.5) has been implicated. In addition to traditional risk factors hyperhomocysteinemia (HC) has been recognized in many parts of China related to risk of stroke. METHODS: To evaluate the impact of HC (homocysteine >14µmol/l) and PM2.5 air pollution on atherogenesis in modernizing China, we studied 756 asymptomatic Chinese in China from 1998-2007. PM2.5 exposure, HC, folate, and methylenetetrahydrofolate reductase (MTHFR) C/T genotype were evaluated. Brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) were measured by ultrasound. Locations were categorized as zones 1, 2 and 3, with increasing PM2.5 exposure. RESULTS: HC was higher (19.4±13.1 and 27.1±25.1µmol/l) in high PM2.5-polluted zones 2 and 3 than in zone 1 (9.7±4.5µmol/l, p<0.0015). The top HC tertile was characterized by lower folate and vitamin B12, but a higher proportion of the MTHFR TT genotype, Metabolic Syndrome (MS) and PM2.5 level (p=0.0018). FMD was significantly lower (7.3±2.3%) and carotid IMT thicker (0.63±0.12mm) in the top HC tertile, compared with low HC tertile (8.4±2.5%, p<0.0001; 0.57±0.1mm, p<0.0001 respectively). Similar differences in FMD and IMT were seen in zones 2 and 3, compared with zone 1 (p<0.0001). On multivariate regression, HC was related to male gender (beta=0.106, p=0.021), MTHFR-TT (beta=0.935, p<0.0001), locations (beta=0.230, p<0.0001) and folate-MTHFR interaction (beta=-0.566, p<0.0001). FMD was related to age (beta= -0.221; p<0.0001), male gender (beta= -0.194, p=0.001) PM2.5 and location (beta=-0.285 to -0.303, p<0.0001). Carotid IMT was related to PM2.5 (beta=0.173, p<0.0001), HC (0.122, p=0.006) but not to MTHFR or location, independent of age, gender, MS, and LDL-C. No significant HC-PM2.5 interaction effect on FMD and IMT was observed. CONCLUSION: HC and PM2.5 pollution but not MTHFR genotype were both related to carotid IMT, independent of other traditional risk factors. This has potential implications in dietary and AP strategies for atherosclerosis prevention in China.

[Effect of EIT-guided individualized PEEP setting on the incidence of hypoxemia in elderly patients undergoing robot-assisted radical prostatectomy].

Objective: To investigate the effect of individualized positive end expiratory pressure (PEEP) setting guided by chest electrical impedance tomography (EIT) on the incidence of hypoxemia in elderly patients undergoing robot-assisted radical prostatectomy in the post anesthesia care unit (PACU). Methods: From September 2020 to October 2021, sixty elderly patients, with the American Association of Anesthesiologists (ASA) of Grade Ⅰ to Ⅲ, who underwent selective robot-assisted radical prostatectomy under general anesthesia in the Cancer Hospital Affiliated to Fudan University were selected. The participants were divided into two groups by the minimum randomized grouping method: EIT-PEEP group (EP group, n=30) and fixed PEEP group (FP group, n=30). After completion of tracheal intubation and establishment of pneumoperitoneum flexion posture, the individualized PEEP setting was guided by EIT in EP group, and the PEEP setting in FP group was 5 cmH2O (1 cmH2O=0.098 kPa) to the end of operation. During the operation, the ventilation mode of pressure regulation volume control was adopted. The driving pressure, dynamic lung compliance (Cdyn), oxygenation index and hemodynamics were recorded at 5 min (T1), 30 min (T2), 60 min (T3) after PEEP setting and at the time of tracheal catheter removal (T4) in both groups. The primary end point was the incidence of hypoxemia in PACU after extubation. Results: The incidence of hypoxemia after extubation was 3.3% (1/30) in EP group and 26.7% (8/30) in FP group (P=0.030). The difference of driving pressure between the two groups at T2 [(13.1±2.4) cmH2O vs (14.9±2.9) cmH2O, P=0.012], T3 [(12.7±2.4) cmH2O vs (15.6±2.8) cmH2O, P<0.001] was statistically significant. In EP group, Cdyn was improved at T2 [(38.4±7.2) ml/cmH2O vs (31.9±5.2) ml/cmH2O, P=0.006] and T3 [(37.5±9.0) ml/cmH2O vs (30.4±5.9) ml/cmH2O, P=0.001]. In EP group, PaO2/FiO2 increased at T1 [(465.7±84.5) mmHg vs (383.5±58.0) mmHg, 1 mmHg=0.133 kPa, P<0.001], T2 [(504.7±105.8) mmHg vs (418.9±73.7) mmHg, P=0.001], T3 [(520.7±92.2) mmHg vs (423.2±90.7) mmHg, P<0.001], T4 [(368.7±42.0) mmHg vs (339.5±54.9) mmHg, P=0.024]. Conclusion: The individualized PEEP setting guided by EIT can reduce the incidence of hypoxemia in elderly patients undergoing robot assisted radical prostatectomy in PACU.

[Clinical pathological features of 180 cases with primary esophageal malignant melanoma].

Objective: To investigate the clinical pathological and epidemiological characteristics of primary esophageal malignant melanoma (PMME). Methods: The clinical pathology data of 180 PMME patients in the esophageal cancer database of the key laboratory of esophageal cancer research in Henan Province from 1973 to 2016 were collected, of which 136 were male, aged (58.5±9.0) years, 44 were female, aged (56.7±12.2) years. Kaplan-Meier and Log rank test were used for survival analysis, Cox regression scale model was used for risk factor analysis. Results: The incidence of PMME is 0.036% (180/500, 000), mostly were male (about 3∶1 for men: female). The common sites of PMME were the lower part of the esophagus (48.9%, 85/174), followed by the middle section of the esophagus (46.0%, 80/174) and the upper part of the esophagus (5.2%, 9/174). No black particles were seen in the PMME cells of 3 patients under microscope, and strong positive expressions of Melan-A and HMB453 were observed in these 3 patients by immunohistochemical results. Of the 129 patients who had a routine preoperative esophageal biopsy, 69 were undiagnosed with PMME (53.5%). The medium survival time of the whole group was 7.9 months, and the survival rates of 1, 2, 3, 5 years were 25.0%, 7.9%, 6.6% and 1.3%, respectively. The univariate analysis showed that N, M, TNM phase and radiotherapy were related to the overall survival of patients (P<0.05). Multivariate analysis showed that TNM phase and radiotherapy were the independent risk factors for overall survival of patients (P<0.05). Conclusions: PMME is more common in men, the common site of the disease is the lower part of the esophagus. The preoperatively missed diagnosis rate of Chinese PMME is high. TNM phase and radiotherapy are the independent risk factors for overall survival of patients.

[Nodal lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia: a clinicopathological and prognostical study].

Objective: To study the clinicopathological features and prognosis of nodal lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia (n-LPL/WM). Methods: A total of 19 cases of n-LPL/WM were collected from May 2009 to January 2020 at First Affiliated Hospital of Zhengzhou University. The clinicopathologic features, immunophenotype, Ig gene rearrangement (BIOMED-2), MYD88 L265P mutation status (by Sanger sequencing) and follow-up data (by telephone) were analyzed. Results: There were 15 males and 4 females with a median age of 61 years (range 43 to 82 years). There were 14 WM and five LPL. The most common symptoms were weakness, fatigue (9/19) and B symptoms (11/19). Majority of the patients (16/18) presented with systemic multiple lymphadenopathies. Eighteen patients presented at advanced stages (Ⅲ/Ⅳ stage). Serum M protein status was IgM (15 cases), IgG (1 case), IgA (1 case) and no-secretory type (2 cases). Seventeen patients had bone marrow involvement. Morphologically, all 19 cases were divided into two groups: typical group (9 cases) or atypical group (10 cases). In the typical group, the structures of the lymph nodes were preserved; the neoplastic cells were predominantly plasmacytoid lymphocytes or mixed small lymphocytes, plasmacytoid lymphocytes and plasma cells, without proliferation of FDC network and follicular implantation. In the atypical group, the tumor showed effaced nodal architecture (5 cases), mainly proliferation of small lymphocytes (6 cases), FDC proliferation and/or follicular implantation (6 cases), marginal zone B cell differentiation (4 cases) and diffuse amyloidosis (1 case). Hemosiderin deposition (19 cases), infiltration of fatty tissue (19 cases) and interstitial sclerosis (9 cases) were commonly seen in both groups. Immunohistochemically, the neoplastic B cells expressed CD20 and CD79α, and the neoplastic plasma cells were positive for CD38, CD138 and MUM-1; eight cases showed light chain restriction; of the seven detected cases, five expressed IgM and the other two expressed IgG and IgA respectively; four cases expressed CD23 weakly, Ki-67 index was 10%-30%. MYD88 L265P mutation was seen in 18/18 cases. There was no significant difference in clinicopathologic features and prognosis between the two groups (P>0.05). The median follow-up time was 61 months, 11 patients were alive, while eight died; the 5-year survival rate was 21.1%. Conclusions: n-LPL/WM is rare, but patients usually present in advanced stages. It is easily confused with other small B-cell lymphomas with plasma cell differentiation, especially basing on morphologic features alone; thus the accurate diagnosis of n-LPL/WM requires a combination of clinical features, serum M protein, immunohistochemistry, bone marrow morphology,flow cytometry and MYD88 L265P mutation status etc. The prognosis of n-LPL/WM may be not very good, and further studies with more cases are needed.

The impact of particulate matter air pollution (PM2.5) on atherosclerosis in modernizing China: a report from the CATHAY study.

BACKGROUND: Air pollution has been associated with an increase in cardiovascular diseases incidence. To evaluate whether air pollution can accelerate atherogenic processes, we assessed the effects of air pollution on important surrogate markers of atherosclerosis [brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT)]. METHODS: A total of 1656 Han Chinese (mean age 46.0 + 11.2 years; male 47%) in Hong Kong, Macau, Pun Yu, Yu County and the 3-Gorges Territories (Yangtze River) were studied between 1996 and 2007 [Chinese Atherosclerosis in the Aged and Young Project (the CATHAY Study)]. Cardiovascular risk profiles were evaluated. Particulate matter with an aerodynamic diameter <2.5 µm (PM2.5) parameters were computed from satellite sensors. Brachial FMD and carotid IMT were measured by ultrasound. RESULTS: Health parameters [age, gender, body mass index, waist : hip ratio (WHR) and glucose)] were similar in lowest and highest PM2.5 exposure tertiles, systolic and diastolic blood pressures and triglycerides were higher (P < 0.001) and low-density cholesterol (LDL-C) was lower in the top PM2.5 tertile (P < 0.001). Brachial FMD [7.84 ± 1.77, 95% confidence interval (CI) 7.59-8.10%, vs 8.50 ± 2.52, 95% CI 8.23-8.77%, P < 0.0001) was significantly lower and carotid IMT (0.68 ± 0.13 mm, 95% CI 0.67-0.69 mm vs 0.63 mm ± 0.15 mm 95% CI 0.62-0.64 mm; P < 0.0001) was significantly thicker in the top PM2.5 tertile compared with the lowest tertile. On multiple regression, FMD was inversely related to PM2.5 (beta = 0.134, P = 0.015) independent of gender, age and blood pressure (model R2 = 0.156, F-value = 7.6, P < 0.0001). Carotid IMT was significantly correlated with PM2.5 exposure (beta = 0.381, P < 0.0001) independent of age, location, gender, WHR, blood pressure and LDL-C (model R2 = 0.408, F-value = 51.4, P-value <0.0001). CONCLUSIONS: Air pollution is strongly associated with markers of early atherosclerosis, suggesting a potential target for preventive intervention.

Randomized clinical trial of continuous transversus abdominis plane block, epidural or patient-controlled analgesia for patients undergoing laparoscopic colorectal cancer surgery.

BACKGROUND: The optimal analgesia regimen after laparoscopic colorectal cancer surgery is unclear. The aim of the study was to characterize the beneficial effects of continuous transversus abdominis plane (TAP) blocks initiated before operation on outcomes following laparoscopic colorectal cancer surgery. METHODS: Patients undergoing surgery for colorectal cancer were divided randomly into three groups: combined general-TAP anaesthesia (TAP group), combined general-thoracic epidural anaesthesia (TEA group) and standard general anaesthesia (GA group). The primary endpoint was duration of hospital stay. Secondary endpoints included gastrointestinal motility, pain scores and plasma levels of cytokines. RESULTS: In total, 180 patients were randomized and 165 completed the trial. The intention-to-treat analysis showed that duration of hospital stay was significantly longer in the TEA group than in the TAP and GA groups (median 4·1 (95 per cent c.i. 3·8 to 4·3) versus 3·1 (3·0 to 3·3) and versus 3·3 (3·2 to 3·6) days respectively; both P < 0·001). Time to first flatus was earlier in the TAP group (P < 0·001). Visual analogue scale (VAS) scores during coughing were lower in the TAP and TEA groups than the GA group (P < 0·001). Raised plasma levels of vascular endothelial growth factor C, interleukin 6, adrenaline and cortisol were attenuated significantly by continuous TAP block. CONCLUSION: Continuous TAP analgesia not only improved gastrointestinal motility but also shortened duration of hospital stay. A decreased opioid requirement and attenuating surgical stress response may be potential mechanisms. Registration number: ChiCTR-TRC-1800015535 ( http://www.chictr.org.cn).

ANTECEDENTES: El régimen analgésico óptimo para los pacientes tras cirugía laparoscópica del cáncer colorrectal se desconoce. El objetivo de este estudio fue caracterizar los efectos beneficiosos del bloqueo continuo del plano transverso abdominal (transversus abdominis plane, TAP) iniciado preoperatoriamente sobre los resultados después de cirugía laparoscópica del cáncer colorrectal. MÉTODOS: Los pacientes sometidos a cirugía del cáncer colorrectal fueron divididos aleatoriamente en tres grupos: anestesia combinada general-TAP (grupo TAP), anestesia epidural combinada general-torácica (grupo TEA) y anestesia general estándar (grupo GA). El resultado primario fue la duración de la estancia hospitalaria. Los resultados secundarios incluyeron la motilidad gastrointestinal, puntuaciones de dolor y niveles plasmáticos de citocinas. RESULTADOS: En total, 180 pacientes fueron aleatorizados y 165 completaron el ensayo. El análisis por intención de tratar mostró que la duración de la estancia hospitalaria en el grupo TEA fue significativamente más larga que en el grupo TAP y GA respectivamente (4,1 (3,8-4,3) versus 3,1 (3,0-3,3) días, P < 0,001; 4,1 (3,8-4,3) versus 3,3 (3,2-3,6) días, P < 0,001). El tiempo hasta la primera eliminación de gases fue más precoz en el grupo TAP (P < 0,001). Las puntuaciones de la escala analógica visual (visual analogue scale, VAS) durante la tos en el grupo TAP y TEA fueron inferiores (P < 0,01). Los niveles elevados en plasma del factor de crecimiento endotelial C (VEGF-C), interleucina (IL)-6, epinefrina y cortisol fueron atenuados significativamente por el bloque TAP continuo. CONCLUSIÓN: La analgesia TAP continua no solo mejora la motilidad gastrointestinal, sino que también acorta la estancia hospitalaria. Una disminución en los requerimientos de opiáceos y la atenuación de la respuesta al estrés quirúrgico podrían ser mecanismos potenciales de la acción de TAP.

[Value of two left atrium and pulmonary vein stereoscopic imaging reconstruction methods on guiding radiofrequency ablation for atrial fibrillation].

Objective: To compare the value of two 3D imaging reconstruction methods for left atria and pulmonary vein on guiding the catheter ablation for atrial fibrillation (AF). Methods: From January 2014 to January 2017, a total of 100 drug refractory paroxysmal AF patients were divided into left atria direct angiography group (n=50), and indirect angiography group (n=50). 3D CARTO system was applied for mapping and guiding the ablation procedure. Patients assigned to direct angiography group were treated as follows: intraoperative puncture of atrial septum, inject contrast agent directly into the left atrium, conduct left atrial and pulmonary venous rotation angiography, reconstruct three-dimensional image, integrate the image into real-time X-ray system to facilitate circumferential pulmonary vein isolation. Patients assigned into the indirect angiography group were treated as follows: inject contrast agent through the right ventricle, conduct delayed rotation angiography of the left atria and pulmonary vein to guide circumferential pulmonary vein fixation and ablation. The left atrial and pulmonary venous image acquisition, the operation and X-ray exposure time, the success rate and the incidence of complication of the two groups were compared. The patients were followed up for 3-6 months. Results: General clinical characteristics of the two groups were similar(all P>0.05). Ablation was successful in all 100 patients. The operation time[(112.0±21.4)min vs. (134.0±24.3)min]and X-ray exposure time((10.7±4.7)min vs. (15.8±5.2)min)were significantly lower in direct angiography group than in indirect angiography group (both P<0.01). There was no significant difference between the two groups in the immediate (86%(43/50) vs. 82%(41/50), P=0.59) and short-term (76%(38/50) vs. 72%(36/50), P=0.65) success rate and complication rate (1 aneurysm in the direct angiography group, 1 pericardial tamponade in the indirect angiography group). In-hospital mortality was zero percent. Conclusion: It is safe and effective method to guide the radiofrequency catheter ablation of paroxysmal atrial fibrillation by reconstruction 3D image of left atrium and pulmonary vein. Compared with indirect angiography group, direct angiography group can improve the imaging quality of left atrium and pulmonary vein, decrease the X-ray exposure time of the ablation procedure.

Blood service in the Tibetan regions of Garzê and Aba, China: a longitudinal survey.

BACKGROUND: Garzê and Aba form the second largest Tibetan-inhabited area of China. Blood services have never been reported for this region before. OBJECTIVE: To assess the current situation and analyse whether a safe and adequate blood supply has been developed in both Garzê and Aba. METHODS: We conducted a longitudinal survey covering the period 2011-2016. The subjects of interest were recruited from non-remunerated voluntary donation, blood testing, clinical transfusion practices and infrastructure of local blood service systems. RESULTS: The donation rate and blood collection volume were below the average levels of both the Sichuan Province and mainland China. Component therapy was widely used, but inappropriate usage of whole blood existed. A lack of national specific standards for people on the plateaus led to local blood transfusions being conducted without full clinical assessment. Endemic and frequently occurring disease, such as hydatid disease and gastrointestinal disease, were inevitable risks for blood utilisation and safety. The potential influence of religious belief and traditions, like 'male-leaving marriages', of Tibetans on donor recruitment and blood safety requires further research. CONCLUSIONS: A relatively safe and complete blood service system has been developed in this region. However, there is still an urgent need for comprehensive and effective support from the government in terms of policies and finance. As an epidemic area of hydatid disease and sexually transmitted disease, this region needs to emphasise public health measures, such as blood safety and inappropriate usage of blood products.

[A multicenter prospective controlled study of catheter ablation for patients with persistent atrial fibrillation using domestic 3D cardiac electrophysiological mapping system].

OBJECTIVE: To verify the safety and efficacy of the domestic 3D cardiac electrophysiological mapping system for catheter ablation of persistent atrial fibrillation (AF). METHODS: From December 2011 to April 2014, 255 patients (184 male) with persistent AF in 13 centers were enrolled in this multicenter prospective controlled study.The patients were allocated to catheter ablation group (experiment group) and antiarrhythmics drugs cardioversion group (control group) with the ratio 2∶1 according to the patients' intention. Left atria were constructed with 3D cardiac electrophysiology mapping system, magnetic sensored saline irrigated radiofrequency ablation catheter (FireMagic™ Cool 3D) and surface reference (Columbus™). Pulmonary vein isolation and left atrial roof line, mitral annulus isthmus line, three tricuspid annulus isthmus line, superior vena cava, the coronary sinus and complex atrial fragmented potentials were targeted if necessary under the guidance of the 3D mapping system. Antiarrhythmics drugs (except amiodarone) were applied to patients for 2 to 3 months after ablation. The patients were followed up for 9 months after 3 months blanking period. The patients in the control group underwent cardioversion with amiodarone and electrical cardioversion if needed. Patients in the control group were also followed up for 9 months. RESULTS: Of the 255 patients, 167 cases were in the experiment group and 88 cases were in the control group. In per protocol set (PPS), 155 cases were in the experiment group, 79 cases in the control group. Catheter ablation was successful for all patients in the experiment group under the guidance of the 3D cardiac electrophysiological mapping system. Pumononary veins isolation was achieved in all patients. After 9 months follow-up beyond blanking period, in full analysis set, the success rate was 66.5% (111/167) in the experiment group, which was significantly higher than that in the control group (21.6% (19/88), P<0.001). In PPS, the success rate was also significantly higher in the experiment group than in the control group (67.1% (104/155) vs. 22.8%(18/79), P<0.001). The incidence of adverse events was 19.8% in the experiment group and 13.6% in the control group(P=0.223). The adverse events associated with catheter ablation included 1 case of left subclavian hematoma, 1 case of left subclavian bleeding and 1 case of pericardial effusion, which was alleviated by pericardiocentesis. No pulmonary vein stenosis occurred. CONCLUSION: Domestic 3D cardiac electrophysiological mapping system can safely and effectively guide catheter ablation of persistent AF.

[Effects of Ido1 on mouse decidualization].

Indoleamine 2,3-dioxygenase 1 (Ido1) is a rate-limiting enzyme which converts the essential amino acid tryptophan to kynurenine. The aim of this study was to investigate the expression and regulation of Ido1 in mouse uterus during decidualization. The results showed that Ido1 mRNA expression gradually increased from day 1 to 4 of pregnancy and reached the peak level on day 4. On days 5-8 of pregnancy, a low level of Ido1 expression was observed in the uteri. Simultaneously, Ido1 mRNA was also lowly expressed in the decidualized uterus and the stromal cells treated with 8-Br-cAMP. Under in vitro decidualization, the expression of Ido1 mRNA gradually declined. Further studies found that overexpression of Ido1 can inhibit the expression of decidualization marker genes PRL, IGFBP1 and Dtprp under in vitro decidualization while inhibition of Ido1 with L-1-MT can induce the expression of these marker genes. Ido1 can prevent uterine stromal cells proliferation and enhance the expression of the Bax gene and increase the Bax/Bcl2 ratio under in vitro decidualization. Additionally, Ido1 can also modulate the expression of the MMP2 gene. In the uterine stromal cells, estrogen and progesterone can stimulate the expression of Ido1. These data indicate that Ido1 may play an important role during mouse decidualization and may be regulated by estrogen and progesterone in the uterine stromal cells.

Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease

Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD.

Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease.

Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD.

Significance of white blood cell count and its subtypes in patients with acute coronary syndrome.

BACKGROUND: Inflammation plays a role in the pathogenesis of coronary atherosclerosis. MATERIALS AND METHODS: Six hundred twenty-three patients with acute coronary syndrome (ACS) referred for coronary angiography for the first time in our hospital were enrolled in this study. White blood cell and its subtypes were measured on admission. The study population was divided into three groups based on total white blood cell count and followed up. Clinical end points were major adverse cardiac events (MACEs), including cardiogenic death, stroke, heart failure, non-fatal myocardial infarction, rehospitalization for angina pectoris. RESULTS: The median age was 68 years (range 31-92) and 64.2% of the patients were men. The median white blood cell count was 6.48 x 10(9 )L(-1) (range 2.34-27.10 x 10(9 )L(-1)). The median follow-up duration was 21 months (range 1-116) and MACEs occurred in 167 patients. The multivariable Cox proportional hazards regression model revealed that neutrophil count [Relative risk = 1.098, 95% Confidence interval (CI): 1.010-1.193, P = 0.029) was a risk factor for MACEs. The logistic regression model revealed that lymphocyte count [Odds ratio (OR) = 1.075, 95% CI: 1.012-1.142, P = 0.018] and monocyte count (OR = 8.578, 95% CI: 2.687-27.381, P < 0.001) were predictive of stenosis >or= 75%; Neutrophil proportion (OR = 1.060, 95% CI: 1.007-1.115, P = 0.026), monocyte count (OR = 12.370, 95% CI: 1.298-118.761, P = 0.029) were predictive of the presence of multivessel disease. Kaplan-Meier analysis of short-term and long-term cumulative survival showed no significant statistical differences among three groups. CONCLUSIONS: Neutrophil count adds prognostic information to MACEs in ACS. Monocyte count and lymphocyte count are predictive of severity of coronary atherosclerosis.

Clinical features of hepatic myelopathy in patients with chronic liver disease.

AIM: To determine the clinical features of hepatic myelopathy (HM), a rare condition associated with chronic liver disease (CLD), in patients in the city of Harbin, China. METHODS: The medical files of 13 patients with HM were selected from 500 randomly chosen files of CLD patients registered in four Harbin hospitals. General information on all cases was summarised and clinical features were compared between HM positive patients (HM group) and HM negative CLD patients (control group). Detailed analysis of the clinical characteristics of HM positive patients was undertaken. RESULTS: The patients in the HM group ranged in age from 41-50 years, which did not differ significantly from the control group. However, the sex ratio in the HM group (12 males/1 female) was significantly higher (p<0.05) than in the control group (342 males/145 females).The most frequent underlying aetiology was post type B hepatitis (12 cases). All cases in the HM group had a history of relapsing hepatic encephalopathy (HE) before or after HM onset, and showed electroencephalographic (EEG) abnormalities; however, the results of spinal cord magnetic resonance imaging were negative, and cerebrospinal fluid analysis findings were normal. Except for clinical manifestations of bilateral lower limb spastic paralysis, the two groups did not differ significantly in regard to other symptoms or signs. Hypoproteinaemia (positive predictive value (PPV) 5.69%, negative predictive value (NPV) 99.65%), blood ammonia elevation (PPV 5.29%, NPV, 99.32%) and abnormal EEG (PPV 5.00%, NPV 100.00%) were sensitive and specific for HM diagnosis. CONCLUSION: In Harbin, HM is found mainly among middle aged men with CLD caused by viral hepatitis and accompanied by relapsing onset of HE. Bilateral lower limb spastic paralysis with hypoproteinaemia, blood ammonia elevation and/or abnormal EEG are significant diagnostic indicators of HM.

Expression of interleukin-17 in ischemic brain tissue.

Ischemic brain injury is acute local inflammation, leading to accumulation of pro-inflammatory cytokines. Cytokines influence the recruitment of leucocytes and play a key role in the inflammatory injury processes. Recently, a number of studies have demonstrated a close relationship between brain ischemia and cytokines. Interleukin-17 (IL-17) is a newly identified T-cell-specific cytokine. In this study, we evaluated the source and the action of IL-17 over the course of cerebral ischemia in rats (Sprague-Dawley) and humans. The levels of IL-17 in the ischemic hemisphere of the human brain, which was removed at necropsy, were assayed immunohistochemically. In rats, permanent middle cerebral artery occlusion (pMCAO) was obtained by inserting nylon monofilament into the right external carotid artery, occluding the right middle cerebral artery. The expression of IL-17 mRNA in rat was assayed using oligoprobe in situ hybridization. IL-17 production by neuroglial cells was assayed by double-staining using antibody glial fibrillary acidic protein (GFAP) and antibody IL-17. Levels of IL-17 were elevated in the ischemic hemispheres of human brain compared with the opposite normal hemispheres and peaked at days 3-5 after brain ischemia. The IL-17-positive cells were found in the ischemic lesion region. IL-17 mRNA was also elevated in ischemic hemispheres of pMCAO-operated rats, which were slightly elevated after 1 h and peaked at 6 days. IL-17 and GFAP double-stained were extensive in rat ischemic hemisphere. The ischemia-induced IL-17 expression in human brain reported here for the first time was very similar to that in rat model except that the peak was slightly earlier. We found for the first time that IL-17 was involved in an intense inflammatory reaction of brain ischemic injury in human. In pMCAO-operated rats, our findings suggest that IL-17 is produced by the neuroglial cells in the brain region undergoing ischemic insult. We suggest that in additional to T cells the neuroglial cell may be another cellular origin of IL-17 in later progression of brain ischemia.

TSPY is a cancer testis antigen expressed in human hepatocellular carcinoma.

In search for genes associated with hepatocellular carcinoma (HCC) by cDNA microarray, we found that the transcription of TSPY, 'testis-specific protein Y-encoded', was upregulated in HCC. Investigation of a broad spectrum of normal and malignant tissues by RT-PCR revealed the TSPY transcript selectively expressed in normal testis, different histological types of human neoplastic tissues, and tumour cell lines. The expression of TSPY in cancer cells was further confirmed by in situ hybridisation. Indirect immunofluorescence microscopy analysis showed that TSPY was localised mainly in the cytoplasm of transiently transfected cells. Testis-specific protein Y-encoded was detected in 50% (16 of 32) of well- and moderately differentiated HCC patients, in 16% (four of 25) of poorly differentiated HCC patients, and in 5% (one of 19) of renal cell cancer patients. A serological survey revealed that 6.6% (seven of 106) HCC patients had anti-TSPY antibody response, demonstrating the immunogenicity of TSPY in humans. In conclusion, these data suggest that TSPY is a novel cancer/testis (CT) antigen and may be a potential candidate in vaccine strategy for immunotherapy in HCC patients.

Identification and analysis of tumour-associated antigens in hepatocellular carcinoma.

To identify tumour and tumour-associated antigens in patients with hepatocellular carcinoma (HCC) one may find potential diagnostic markers and immunotherapeutic targets. In the current study, 30 distinct antigens reactive with serum IgG from HCC patients were identified by serological analysis of cDNA expression libraries (SEREX). The mRNA expression patterns of 14 of these 30 antigens were altered in cancer as further revealed by cDNA microarray, with upregulation for nine and downregulation for five antigens. One of the upregulated antigens was cancer-testis (CT) antigen (CAGE), which had been previously reported to be expressed exclusively in normal gametogenic tissues and aberrantly expressed in a variety of cancer cells. In our study, CAGE mRNA was expressed in 39.4% of HCC patients, 73.3% of patients with gastric cancer and 30.8% of patients with colorectal cancer. Antibodies against CAGE protein were detected in approximately 5.1% of the sera from HCC patients, 8.3% of that from gastric cancer patients and 7.3% of that from colorectal cancer patients. The relative high incidence of CAGE in cancer cells makes it a potential target for vaccine design. Another antigen of great interest is transgelin 2. The overexpression of transgelin 2 mRNA in a large per cent (69%) of HCC points to its potential as a diagnostic marker for HCC.

Association of beta-adrenoceptor single nucleotide polymorphisms with resting heart rate.

The association of beta-adrenoceptor (B-AR, including three subgroups: Beta1, Beta2 and Beta3) single nucleotide polymorphisms (SNP) with resting heart rate (RHR) were analyzed. RHR of 107 healthy subjects in the supine were detected by computerized system for 8 minutes. Genotyping SNPs of S/G49 and R/G389 of Beta1-AR and W/R64 of Beta3-AR in these subjects were by means of PCR-restriction fragment length polymorphism (PCR-RFLP) technique. Genotyping SNPs of R/G16 and Q/E27 of Beta1-adrenoceptor in these subjects were by means of allele specific primer-PCR (ASP-PCR) technique. It was found that there was no significant difference among RHRs corresponding above SNPs of B-AR, but the SNP of R/G389 of Beta1-AR, in which there was significant difference among RHRs (P<0.05). Either in the female individuals or in the male, those with Beta1-AR G/G389 genotype had the highest RHR. The females with R/R389 genotype had the lowest RHR, however, the males with R/G389 genotype had the lowest RHR. The RHR was not only associated with R/G389 polymorphism of Beta1-adrenoceptor gene significantly, but also was associated with gender in Chinese.