[The comparison between endoscopic and surgical treatment of delayed iatrogenic bile duct injury by propensity score matching].

Objective: To compare the safety and clinical efficacy of endoscopic and surgical treatment of patients with delayed iatrogenic bile duct injury (DBDI) with severity (SG) grade 1 to 2. Methods: The clinical data of 129 patients with SG grade 1 to 2 DBDI who received endoscopic or surgical treatment in the First Hospital of Lanzhou University from November 2007 to November 2021 were retrospectively collected. There were 46 males and 83 females,aged (M(IQR)) 54(22)years(range: 21 to 82 years). The baseline data of the two groups were matched 1∶1 by propensity score matching(caliper value was 0.2). Independent sample t test,rank sum test,χ2 test or Fisher exact probability test were used to analyze the data of the two matched groups. Results: There were 48 patients in each of the endoscopic treatment and surgical groups after matching,and there was no difference in general information between the two groups(both P>0.05). The bile duct injury-repair interval and intraoperative anesthesia complications were not statistically significant between the two groups after matching(all P>0.05). Compared with the surgical group, patients in the endoscopic treatment group had significantly shorter operative time(50 (30) minutes vs. 185 (100) minutes, Z=7.675,P<0.01) and postoperative hospital stay(5 (5) days vs. 12 (7) days, Z=5.848, P<0.01).For safety,there was no statistical difference in the incidence of immediate postoperative complications between the two groups with Clavien-Dindo classification of surgical complications<Ⅲ;the incidence of serious postoperative complications (Clavien-Dindo classification of surgical complications≥Ⅲ) was significantly higher in the surgical group than in the endoscopic treatment group(P=0.012). The incidence of long-term postoperative complications was not statistically different between the two groups(28.1% vs. 20.7%,P=0.562). In terms of efficacy,the postoperative liver function indexes of patients in both groups improved significantly compared with the preoperative period and returned to normal or near normal levels; the postoperative infection indexes of both groups showed an increasing trend,but were within the normal range. Of the 96 patients in both groups,61 obtained follow-up,and the follow-up time was (89.4±48.0)months(range: 3 to 165 months),and there was no statistical difference between the two groups(P=0.079). The probability of excellent long-term follow-up (78.1% vs. 86.2%) was not statistically different between the two groups(P=0.412).In patients with Strasberg-Bismuth type E1,the probability of excellent long-term follow-up was higher in the endoscopic treatment group compared with the surgical group(13/14 vs. 2/5,P=0.037). Conclusions: For DBDI patients with SG grade 1 to 2 and bile duct continuity,endoscopy can be used as the first deterministic treatment. The advantages of endoscopic therapy compared to surgery are the lower incidence of postoperative serious complications,and the shorter duration of surgery and postoperative hospital stay.

[Recurrence and metastasis of pheochromocytoma/paraganglioma after tumor resection and clinical characteristics analysis].

Objective: The purpose of this study is to investigate the incidence of recurrence or metastasis of pheochromocytoma/paraganglioma (PPGL) patients after primary tumor resection, and to compare the differences of clinical indicators between patients with or without recurrence or metastasis. Methods: This study is a retrospective study. All 157 patients were followed up after tumor resection in Peking Union Medical College Hospital from 2008 to 2016. We obtained the basic information [age of diagnosis, gender, height, weight and body mass index (BMI)], the onset status of PPGL (age of onset, course of disease, family history, tumor location, whether the tumor is bilateral or multiple, and preoperative blood pressure), clinical and pathological features of PPGL tumor (tumor size, whether it could adhere, invade or infiltrate during operation, whether the tumor capsule is smooth and complete on the postoperative pathological diagnosis, whether there is infiltration growth and cystic necrosis on tumor pathology and Ki-67 index), and laboratory examination results [24 hours urinary norepinephrine (NE), epinephrine (E), dopamine (DA) before operation]. According to the outpatient or telephone follow-up, the postoperative incidences of recurrence and metastasis were explored, and the basic information, status of onset, clinical and pathological characteristics of tumors, and laboratory test results of patients were compared. Results: A total of 157 patients, 69 males and 88 females, were with an average age of (42.4±13.4) years old. There were 103 patients with PCC and 54 with PGL. The average follow-up time was (9.5±2.0) years. Of the 103 patients with PCC, 13 (12.6%) had postoperative recurrence and 9 (8.7%) had distant metastasis. Compared with the patients without recurrence and metastasis, the onset age of the 13 patients with recurrence was younger [(27.3±15.7) years vs (39.3±12.2) years, P=0.003], the course of disease was longer [48.0 (23.0, 141.0) months vs 12.0 (4.0, 60.0) months, P=0.010]. The tumor size of 9 patients with distant metastasis was larger [8.0 (6.1, 12.8) cm vs 5.0 (4.0, 7.0) cm, P=0.027]. Of the 54 patients with PGL, 8 (14.8%) had postoperative recurrence and 5 (9.3%) had distant metastasis. Compared with the patients without recurrence and metastasis, the course of disease of the 8 patients with recurrence was longer [90.0 (36.3, 165.0) months vs 24.0 (8.0, 72.0) months, P=0.009], and the proportion of primary tumors with multiple lesions was higher (4/8 vs 4.4%, P=0.003). The preoperative diastolic blood pressure was higher in 5 patients with distant metastasis [(146.0±32.1) mmHg vs (120.6±25.3) mmHg, P=0.043] (1 mmHg=0.133 kPa), and the proportion of primary tumors with multiple lesions was higher (2/4 vs 4.4%, P=0.029). Conclusion: PPGL patients are prone to have recurrence or metastasis. PPGL patients with postoperative recurrence or distant metastasis had younger onset age, longer course of disease, larger tumor size and higher proportion of multiple lesions.

[Differential diagnosis between pulmonary artery sarcoma and central chronic pulmonary thromboembolism:a preliminary study on CT signs].

Objective: To improve the diagnostic accuracy of pulmonary artery sarcoma, and to distinguish it from central chronic pulmonary thromboembolism using CT scans. Methods: In this retrospective study, two groups of pulmonary artery sarcoma (PAS group) and central chronic pulmonary thromboembolism (central CPTE group) confirmed by pathology at our hospital between August 2009 and July 2019 were enrolled, clinical features and pre-operative CT pulmonary artery manifestation were collected, and the key points of differential diagnosis were summarized. Results: The study was composed of 13 cases in the PAS group including 10 males (76.9%), with an average age of (45.4±15.5) years. There were 19 patients in the central CPTE group including 14 males (73.7%), with an average age of (38.6±14.1) years. There were no significant differences in gender and age between the two groups. Deep venous thrombosis in the lower extremities was significantly higher in the central CPTE group than in the PAS group (7/19 vs. 0/13, P=0.025), and the N-terminal pro-brain natriuretic peptide value was higher in the central CPTE group than in the PAS group [674.50(261.70-1 977.70) vs. 66.00(28.10-505.50),P=0.001]. In CT pulmonary angiography, the involvement of the main pulmonary artery, and the proximal lesion showing an acute angle to the pulmonary artery wall were more common in the PAS group [11(84.6%) vs. 5(26.3%), P=0.003; 11(84.6%) vs. 2(10.5%), P<0.001, respectively]. The swelling index of the main pulmonary and the left/right main pulmonary arteries in the PAS group were significantly higher, as well as the dilatation in the lobar and segmental pulmonary arteries [1.19±0.17 vs. 0.99±0.19,P=0.006, 10(76.9%) vs. 2(10.5%), P<0.001, respectively]. The right ventricular transverse diameter/left ventricular transverse diameter (RVd/LVd) and pulmonary artery diameter/ascending aortic diameter ratio (Pad/Aod) were significantly lower in PAS group than those in the central CPTE group (0.97±0.19 vs. 1.23±0.35,P=0.020; 0.98±0.25 vs. 1.15±0.20,P=0.039). Conclusions: In CT pulmonary angiography, filling defects involving the main pulmonary artery and showing expansive growth were highly suggestive of pulmonary artery sarcoma. The history of deep venous thrombosis of the lower extremities was helpful for the diagnosis of chronic pulmonary embolism.

[Relationship between insulin resistance, serum VCAM-1, FGF19, IGF-1 and colorectal polyps].

Objective: To explore the relationship between insulin resistance, glucose and lipid metabolism related molecules and colorectal polyps. Methods: A total of 262 healthy people who underwent colonoscopy in Shandong cancer hospital from June 2019 to September 2020 were selected. The levels of serum vascular cell adhesion molecule-1 (VCAM-1), fibroblast growth factor 19 (FGF19), insulin like growth factor (IGF-1), fasting blood glucose and fasting blood insulin were detected by enzyme-linked immunosorbent assay (ELISA). Insulin resistance index (HOMA-IR) was calculated, and the influencing factors of occurrence, pathological type, size and number of polyps were analyzed. Results: Among 262 cases, 116 cases were polyp free, 113 cases were adenomatous polyp and 33 cases were inflammatory polyp. HOMA-IR, VCAM-1 and FGF19 in polyp group were 2.904±1.754, (334.415±139.573) ng/ml and (135.865±98.470) pg/ml, respectively, which were higher than 2.369±1.306, (302.480±99.946) ng/ml and(110.694±76.044) ng/ml in non-polyp group, respectively (P<0.05). Multivariate Logistic regression analysis showed that the gender (OR=4.269, 95%CI: 1.963-9.405) and FGF19 (77.0-131.4 pg/ml: OR=2.385, 95%CI: 1.155-4.926) were independent factors of colorectal polyps. The gender (OR=3.799, 95%CI: 1.650-8.748) and FGF19 (77.0-131.4 pg/ml: OR=2.290, 95%CI: 1.072-4.891) were independent factors of colorectal adenomatous polyps. The gender(OR=6.725, 95%CI: 1.853-24.410) and fasting plasma glucose (≥6.5 mmol/L: OR=0.047, 95%CI: 0.009-0.245) were independent factors of colorectal inflammatory polyps. The gender (OR=3.539, 95% CI: 1.293-9.689) was an independent factor for the occurrence of single polyp. The gender (OR=5.063, 95% CI: 2.048-12.515), FGF19 (77.0-131.4 pg/ml: OR=2.502, 95%CI: 1.102-5.681), fasting plasma glucose (≥6.5 mmol/L: OR=0.282, 95%CI: 0.095-0.839) were independent factors of multiple polyps. The gender (OR=3.416, 95% CI: 1.134-10.289) and fasting insulin (≥9.4 µU/ml: OR=9.480, 95% CI: 1.485-60.521) were independent risk factors for colorectal polyps<0.5 cm. The gender (OR=3.151, 95%CI: 1.244-7.984) and fasting plasma glucose (≥6.5 mmol/L: OR=0.310, 95%CI: 0.102-0.941) were independent risk factors for colorectal polyps with the size of 0.5-0.9 cm. The gender (OR=22.649, 95%CI: 4.154-123.485), age (55 to 64 years old: OR=4.473, 95%CI: 1.070-18.704; ≥65 years old: OR=5.815, 95%CI: 1.300-26.009), BMI (≥28 kg/m(2): OR=5.310, 95%CI: 1.224-23.032) and FGF19 (77.0-131.4 pg/ml: OR=7.474, 95%CI: 1.903-29.351) were independent factors for colorectal polyps with size ≥ 1.0 cm. Gender stratification analysis showed that FGF19 was an independent factor for the occurrence of male polyps (77.0-131.4 pg/ml: OR=6.109, 95%CI: 1.688-22.104) and adenomas (77.0-131.4 pg/ml: OR=6.401, 95%CI: 1.717-23.864). The age (55 to 64 years old: OR=3.783, 95%CI: 1.052-13.611) and VCAM-1 (≥352.8 ng/ml: OR=4.341, 95%CI: 1.142-16.493) were independent risk factors of female polyps. The age (55 to 64 years old: OR=5.743, 95%CI: 1.205-27.362, ≥65 years old: OR=6.885, 95%CI: 1.143-41.467), VCAM-1 (≥352.8 ng/ml: OR=6.313, 95%CI: 1.415-28.159) and IGF-1 (≥7.6 ng/ml: OR=5.621, 95%CI: 1.069-29.543) were independent factors of female adenoma. Conclusions: The occurrences of colorectal polyps and adenomatous polyps are related to insulin resistance and glucose and lipid metabolism. Serum FGF19 is an independent influencing factor for the occurrence of colorectal polyps and adenomatous polyps, and is a potential serological diagnostic marker and therapeutic target for colorectal polyps and adenomatous polyps.

Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?

AIM: To compare the uniformity and image quality between contrast media injection protocols adjusted for patient body weight (BW) versus body surface area (BSA) during coronary computed tomography (CT) angiography (CCTA). MATERIALS AND METHODS: Consecutive patients (n=489) with suspected coronary artery disease were randomised prospectively to one of two CCTA protocols. In the BW protocol (n=245), patients received individualised iodine delivery rates (≤50 kg: 1 g/s; 51-60 kg: 1.2 g/s; 61-70 kg: 1.4 g/s; 71-80 kg: 1.6 g/s; 81-90 kg: 1.8 g/s; 91-100 kg: 2 g/s; >100 kg: 2.2 g/s). In the BSA protocol (n=244), patients received 9,600 mg iodine/m2 of contrast medium over 12 seconds. Attenuation and image noise were measured. Signal-to-noise ratio and contrast-to-noise ratio were calculated. Image quality was scored. Attenuation was assessed for correlation with BW and BSA using linear regression. RESULTS: There were no statistically significant differences in mean arterial attenuation (396.8±47.6 versus 395.8±42.2 HU, p=0.804; 95% confidence interval: -7 to 9), image noise (25.2±5.8 versus 25.5±5.4 HU; p=0.549), signal-to-noise ratio (16.7±4.4 versus 16.6±3.6; p=0.902), contrast-to-noise ratio (25.1±5.8 versus 25.8±7.4; p=0.258) or image quality scores (4.1±0.9 versus 4±0.9; p=0.770) between the BW and BSA protocols. There was no correlation between BW and aortic attenuation or between BSA and aortic attenuation (p=0.324 and 0.932, respectively). CONCLUSION: The average contrast media attenuation and image quality was comparable between BW-adjusted protocol and BSA-adjusted protocol.

[Function and mechanism of histone demethytransferase Jmjd3 mediated regulation of Th1/Th2 balance through epigenetic modification in pre-eclampsia].

Objective: To observe the expression level of histone demethyltransferase Jmjd3 in patients with pre-eclampsia (PE), and to investigate the possible mechanism of its epigenetic modification in regulating Th1/Th2 imbalance in PE patients. Methods: The mRNA levels of histone demethyltransferase Jmjd3 from peripheral blood mononuclear cells (PBMC) of PE patients and normal pregnant women were detected by RT-PCR. Peripheral serum IFN-γ and IL-4　　were detected by ELISA. RT-PCR was used to detect the mRNA levels of Jmjd3, Tbx21 and Cxcr3 in the spleen of PE and control mice. Immunomagnetic beads were used to sort out the initial CD4+ T cells in the spleen of control and PE mice. Western blot was used to detect H3K27me1 and H3K27me3 levels. ChIP analysis was used for H3K27me3 demethylation modification in spleens of PE mice. Results: Compared with normal pregnant women, the mRNA level of Jmjd3 in PBMC of PE patients was significantly increased, the level of IFN-γ in serum was significantly increased, and the level of IL-4 was significantly reduced (P<0.01). Compared with normal control mice, the mRNA level of Jmjd3 in the spleen of PE mice was significantly increased, and the expression of Tbx21 and Cxcr3 was significantly increased in PE mice (P<0.01); the H3K27me3 level of CD4+ T cells in PE mice was significantly reduced (P<0.05), but H3K27me1 was not changed. ChIP analysis showed that CD4+ T cells H3K27me3 in PE group mice were in the Ifng promoter region, compared with control mice. Recruitment was significantly reduced, while recruitment in the promoter region of Il4 was significantly increased (P<0.01). Conclusions: In both PE patients and mice with PE model, the relative expression level of histone demethyltransferase Jmjd3 is significantly up-regulated, which further induces the demethylation of H3K27me3 in the Ifng promoter region and promotes the initial CD4+ T cells to Th1 cell differentiation and development, leading to an imbalance of Th1/Th2, which may be one of the important reasons for the development of preeclampsia.

[The differential diagnosis for novel coronavirus pneumonia and similar lung diseases in general hospitals].

Novel coronavirus pneumonia was a novel coronavirus infection that has dominated pulmonary infection since December 2019. The main manifestations were fever, dry cough, shortness of breath, normal or leukopenia in peripheral blood and changes in chest CT and in severe cases, multiple organ failure might occur. The National Health Commission, PRC has revised the consensus on diagnosis and treatment seven times in a short period of time, indicating the growing understanding of the disease. Patients with novel coronavirus pneumonia usually had history of travelling or living in the epidemic area including Wuhan within 14 days before onset, or have been exposed to patients who had fever or respiratory symptoms from the epidemic area, or had clustering diseases. However, novel coronavirus pneumonia was becoming more and more blurred after vanishing epidemic. The diagnosis and differential diagnosis of novel coronavirus pneumonia were challenges not only because of large number of tourists increasing dramatically after the relieving of epidemic, but also patients with other diseases from different areas to search for medical care. In this article, the clinical and chest imaging features of the novel coronavirus pneumonia were reviewed and compared with other infections and non-infectious diffuse pulmonary diseases. We try to find the similarities and differences among them, and to identify clues to the diagnosis of novel coronavirus pneumonia, so as to ensure accurate diagnosis and treatment.

Simulation and Sensitivity Analysis of Microtubule-Based Biomechanical Mass Detector.

The microtubule is biologically the most rigid filament that is so critical to the cytoskeleton system. It is significant to study the mass sensitivity of microtubule in order to understand biophysical behaviors, such as the influence of kinesin and dynein moving along microtubules. In this research, the sensitivity of mass detector using individual microtubule is first studied. The frequency shifting of the detector due to mass loads is simulated. The influences of mass load positions and boundary conditions on the mass sensitivity are evaluated. It is predicted in this research that the mass sensitivity of a 1 µm microtubules-based mass detector could reach 10-17 g. Results also show that the resonant frequency decreases logarithmic linearly with the increase of the attached mass regardless of the microtubule length and the position of mass load. Moreover, the sensitivity of resonant frequency shift to the microtubule length is also analyzed.

[Study on the influence of health belief model on the compliance of medical staff with sharp injury protection behavior].

Objective: To explore the effects of the intervention based on the theoretical framework of Health Belief Model on improving sharp injury protection behavior compliance of medical staffs, in order to provide some references for energetically developing blood-borne occupational exposure protection intervention in the region. Methods: According to the inclusion criteria, 178 medical staffs were selected, implemented intervention of the theory of health belief model. Methods included diversity training, experiencing operation, filed observation and supervision and so on, strengthened intervention after 1 month, evaluated the intervention effect after 3 months, used questionnaires and field observation to evaluate the effect before and after the intervention. Results: the scores of security behavior compliance were higher before intervention and there was significant difference (P<0.05) . Observed that, after the intervention the incidence of unsafe behavior in medical personnel dropped from 29.1% to 13.2%, the difference was statistically significant (P<0.05) . Conclusion: The intervenion of the theory of health belief model can strengthen sharp injury protection belief of medical personnels, improve behavior compliance, reduces the occurrence of sharp injury.

[Pulmonary metastatic angiosarcoma presenting with diffuse alveolar hemorrhage: 9 case reports].

Objective: Pulmonary metastatic angiosarcoma is a rare, fatal disease that often presents as diffuse alveolar hemorrhage(DAH). In this report, clinical characteristics of pulmonary metastatic angiosarcoma were retrospectively reviewed. Methods: A total of 9 patients with angiosarcoma who presented as DAH were enrolled. Clinical data included age, gender, symptoms, smoking status, physical exam findings, pulmonary function tests, and radiology. Results: All patients were male with median age 41 years(range, 22 to 57 years). The most common symptom was hemoptysis(9/9). Other symptoms included dyspnea (5/9), cough(3/9), chest pain(3/9), fever(2/9,) and edema of the lower extremity and oliguria(4/9).The common misdiagnoses were tuberculosis(4/9), vasculitis(3/9) and other infection(1/9). Chest computed tomography showed bilateral,random distributed different-sized nodules(9/9),as well as ground-glass areas (9/9).The hearts, mainly right atrium, were the most common primary locations(7/9).Cardiac mass was the first manifestation in five patients by echocardiography(5/8).Two atrial masses were identified by computer tomography pulmonary angiography and magnetic resonance imaging respectively. Transbronchial lung biopsy failed to find malignancy. Computer tomography guided transthoracic needle biopsy was difficult to perform in most patients. Eight patients were diagnosed by surgical biopsy, either by lung biopsy(4/8) or cardiac biopsy(4/8).The median survival period was only 3 months after surgery. Conclusion: Metastatic pulmonary angiosarcoma should be considered in patients with DAH and multiple glass ground opacity and nodules on chest CT. Careful cardiologic monitoring is necessary. Surgical biopsy is reliable for diagnosis.

[Efficacy and safety of anlotinib in 16 patients with advanced non-small cell lung cancer].

Objective: To evaluate the efficacy and safety of anlotinib in patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients with stage ⅢB/Ⅳ NSCLC who progressed after two lines or more regimens were randomized into anlotinib group (12 mg daily from day 1 to 14 of a 21-day cycle) or placebo group with ratio of 2∶1. Study drugs or placebo were given until disease progression or intolerable toxicity. The primary endpoint was overall survival (OS), and the second endpoints were progression free survival (PFS), objective response rate, and disease control rate. Results: Between April 2015 and December 2015, twenty-four patients were assigned at Peking Union Medical College Hospital. The baseline characteristics of the anlotinib group (n=16) and placebo group (n=8) were fairly comparable. The median OS was 12.7 months in anlotinib group and 11.1 months in placebo group (P=0.460).The median PFS was 4.0 months in anlotinib group and 1.4 months in placebo group (P=0.065).The common adverse events were manageable such as hypertension, hand-foot syndrome, thyroiddy sfunction. No drug-related mortality occurred. Conclusions: Anlotinib had a trend of improvement in OS and PFS as third-line treatment or beyond in advanced NSCLC compared with placebo with manageable toxicity. ClinicalTrials:: NCT02388919.

Combined detection of tumor markers and serum inflammatory factors in the diagnosis and treatment of gynecologic oncology.

In recent years, gynecologic cancer has become the third leading cause of death for women world-wide. Serum tumor markers and inflammatory factors have been shown to be useful in the diagnosis of gynecological tumors. Therefore, the clinical value of the combined detection of tumor markers and serum inflammatory factors in the diagnosis of gynecologic oncology was studied. One hundred patients with gynecological tumors admitted to our hospital were selected as the tumor group, and 50 healthy volunteers were selected as the control group. According to clinical diagnosis, the tumor group was divided into a malignant tumor group and a benign tumor group. The levels of CA199, CA125, and CEA in each serum were measured by the Elecsys2010 automatic electrochemiluminescence immunoassay system. The levels of serum TNF-α and IL-17 were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that, when compared with the control group, the levels of CA199, CA125, CEA, TNF-α, and IL-17 in serum of the benign tumor group were significantly increased (P<0.001), and were further increased in the malignant tumor group. Moreover, the positive detection rates of combined detection of CA199, CA125, CEA, TNF-α, and IL-17 for malignant and benign tumors were significantly higher than that of single detection (P<0.05), and the positive detection rate of combined detection of malignant tumors was significantly higher than that of benign tumors (P<0.05). These results indicate that the combined detection of inflammatory factors and tumor markers has a high clinical value in the diagnosis and treatment of gynecological tumors and is worth adopting.

[The clinical characteristics of pulmonary benign metastasizing leiomyoma].

Objective: Pulmonary benign metastasizing leiomyoma (PBML) is a rare entity that leiomyoma of uterus metastasized to the lung. The clinical characteristics of this rare disease were analyzed in this article. Methods: The detailed clinical records of 7 patients diagnosed as PBML at Peking Union Medical College Hospital between January 2001 and June 2015 were reviewed. Results: All patients were women with median age of 44 years (range 28-62). Symptoms included dyspnea (2/7), chest pain (1/7), cyanosis (1/7), cough (1/7) and bloody sputum (1/7), while 4/7 cases were asymptomatic. Six patients had the past-history of leiomyoma of uterus 20 months to 14 years ago among whom 5 patients received hysterectomy. Chest CT showed bilateral, random-distributed multiple round solid nodules, or diffuse-distributed miliary nodules, or single solid nodule, even some small cavities. Extra-pulmonary metastasis was found in left superclavicular lymph node (1 case) and right heart (1 case). Histological tissues were obtained by video-assisted thoracic surgery lung biopsy (4/7), mass resection on tricuspid valve (1/7), transbronchil lung biopsy (1/7), and CT-guided percutaneous lung biopsy (1/7). Pathology showed an interlacing pattern by spindle cells having elongated nuclei without cellular atypia. Ki-67 index was less than 1%. Molecules such as smooth muscle antibody, estrogen receptor (ER) and progestrone receptor (PR) were positive in immunohistochemistry staining. Neither letrozole nor zoladex was effective. Two patients responded to bilateral adnexectomy, presenting as shrunk nodules. No relapsed disease was seen in one patient with single nodule after resection. There was only one patient with disease-related mortality, whose chest CT showed milliary nodules. Conclusion: Although CT findings of PBML are similar to malignancies, the clinical outcome is good. Despite the positive expression of ER and PR, the effectiveness of hormone related treatment is limited. And periodical follow up is suggested even to those uneventful patients.

[The therapeutic value and safety of icotinib as first-line therapy for advanced non-small cell lung cancer patients].

Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%. The median PFS was 14.9 months (95%CI 13.5-16.3) and the OS was 37.0 weeks (95%CI 27.9-46.1). Patients with brain metastases showed higher ORR(P=0.049). Patients with stage ⅢB had longer PFS than those with stage Ⅳ(P=0.007). The most common adverse events were grade 1-2 skin rash (38 patients, 40.9%). Other adverse events included dry skin, oral mucositis, diarrhea and liver function injury. Three patients withdrew because of severe liver injury or skin rash. No treatment related mortality occurred. Conclusions: Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.

[Noninvasive diagnostic and predictive value in renal transplant recipients with acute rejection by measurement of urine Fractalkine].

Objective: To investigate the relationship between early-stage renal acute rejection(AR) and the level of Fractalkine in urine, explore the diagnostic and noninvasive monitoring value in early stage after transplantation by measurement of urine Fractalkine. Methods: Urine samples were examined from renal transplant patients between January 2006 and October 2009. A total of 155 patients were enrolled, including 49 with biopsy-proved AR, 58 patients with stable renal function and no abnormal histological findings, 10 patients with subclinical rejection in protocol biopsy, 9 patients with biopsy-proven acute tubular necrosis and 29 patients with biopsy-proven chronic allograft nephropathy. Additionally, urine samples were also collected from 40 healthy controls. Fractalkine was measured in urine samples using a commercial human Fractalkine enzyme-linked immunosorbent assay (ELISA) kit. Immunohistochemistry for Fractalkine expression was performed on biopsies from renal transplant patients with AR and non-AR. Results: Forty-nine patients with AR excreted urinary Fractalkine at a significantly higher level than levels in patients with stable renal function and healthy controls[(429.1±56.1)vs (94.6±8.4), (84.5±8.9)ng/mmol creatine, both P<0.001]. Patients with AR excreted urinary Fractalkine at a significantly higher level than levels in patients with acute tubular necrosis and chronic allograft nephropathy[(429.1±56.1)vs(133.0±9.8), (183.0±18.9)ng/mmol creatine, both P<0.001]. Receiver operating characteristic(ROC)curve was constructed to determine the discriminatory power of Fractalkine levels for diagnosis of AR. The area under ROC curve was 0.920(95% CI: 0.875-0.969, P<0.001), which showed that Fractalkine was a suitable marker for the diagnosis of AR. At a cut-off point of 157.5 ng/mmol creatinine, the sensitivity was 83.7% and the specificity was 84.5% (P<0.001). The dynamic level of urinary Fractalkine in AR patients within 3 weeks after transplantation fluctuated above 300 ng/mmol creatine, which is remarkably higher than patients with stable renal function (below 200 ng/mmol creatinine). Conclusions: As a noninvasive monitoring method, Fractalkine in urine may be a new approach for detection of AR as well as useful to predict response to antirejection therapy. It has good sensitivity and specificity. Besides, measurement of Fractalkine in urine is a simple, inexpensive method for the routine clinical monitoring after kidney transplantation.

Adenosine inhibits migration, invasion and induces apoptosis of human cervical cancer cells.

Extracellular adenosine is a key signaling molecule which mediates immune suppression, angiogenesis, and regulates cancer cells growth. The effect of adenosine on cervical cancer cells migration and invasion has not been well studied. In the current study, we used Hela and SiHa cell lines to evaluate the effects of adenosine on cervical cancer cells migration, invasion, and apoptosis. The results showed that adenosine treatment inhibited the migration and invasion activities of Hela and SiHa cells. Moreover, by determining the expression of molecules which were involved in epithelial to mesenchymal transition (EMT) progress, we found that epithelial marker E-cadherin was significantly increased in response to adenosine treatment, while the mesenchymal markers including N-cadherin and fibronectin were decreased. These data suggested that adenosine inhibited cervical cancer cells via repressing the EMT progress. The flow cytometry analysis showed that adenosine could also induce cervical cancer cell apoptosis, which mechanism was further confirmed by investigating the expression levels of apoptosis related molecules, via activating mitochondrial apoptosis pathway. These data might suggest that adenosine could be used as an agent for the treatment of cervical cancer.

Sterol regulatory element binding protein-1 (SREBP-1)c promoter: Characterization and transcriptional regulation by mature SREBP-1 and liver X receptor α in goat mammary epithelial cells.

Sterol regulatory element binding protein-1 (SREBP-1) is a key transcription factor that regulates lipogenesis in rodent liver. Two isoforms (SREBP-1a and SREBP-1c) of SREBP-1 are transcribed by an alternative promoter on the same gene (SREBF1), and the isoforms differ only in their first exon. Although the regulatory effects of SREBP-1 on lipid and milk fat synthesis have received much attention in ruminants, SREBP-1c promoter and its regulatory mechanisms have not been characterized in the goat. In the present study, we cloned and sequenced a 2,012-bp fragment of the SREBP-1c 5'-flanking region from goat genomic DNA. A luciferase reporter assay revealed that SREBP-1c is transcriptionally activated by the liver X receptor α (LXRα) agonist T0901317, and is decreased by SREBP-1 small interfering (si)RNA. A 5' deletion analysis revealed a core promoter region located -395 to +1 bp upstream of the transcriptional start site (TSS). Site-directed mutagenesis of LXRα binding elements (LXRE1 and LXRE2) and sterol regulatory elements (SRE1 and SRE2) revealed that the full effects of T 4506585 require the presence of both LXRE and SRE. We also characterized a new SRE (SRE1) and demonstrated a direct role of SREBP-1 (auto-loop regulation) in maintaining its basal transcription activity. Results suggest that goat SREBP-1c gene is transcriptionally regulated by mature SREBP-1 (auto-loop circuit regulation) and LXRα in goat mammary epithelial cells.

Large-scale tissue-specific and temporal gene expression profiles in Pengze crucian carp.

In the present study, the tissue-specific and temporal gene expression profiles of four catalogues of gonadal development-related genes (sex differentiation-related, steroid receptor, steroidogenic, and structural genes) were detected in nine tissues and during 11 successive developmental stages in the Pengze crucian carp (Pcc) (a triploid mono-female gynogenic fish). The results showed that these target genes exhibited overlapping distributions in various tissues, with the exception of Pcc-vasa and Pcc-cyp17a1. Gene expression profiling of the developmental stages showed that all of the target genes simultaneously reached peak expression levels at 40 and 48 days post hatching (dph). Both 40 and 48 dph appeared to be two key time points associated with the process of Pcc gonadal development. These data will provide a clear understanding of gene expression patterns associated with the gonadal development-related genes of this gynogenic teleost.

Effect of hyperphosphatemia on gene expression of the Na-Pi cotransporter in rats.

We investigated the effect of high phosphorus content on the sodium-phosphate cotransporter (NaPi-IIa and NaPi-IIl). Forty-eight Sprague-Dawley rats were divided into 3 groups: high-phosphorus group (HP) with fructose diphosphate sodium injection; self-manufactured low-phosphorus diet group (LP); and normal diet group (NP). At the 1st, 2nd, 4th, and 6th weeks, 4 rats from each group were sacrificed for detecting serum levels of calcium, phosphorus, and intact parathyroid hormone. Semi-quantitative retrovirus-polymerase chain reaction was used to detect the expression of NaPi-IIa and NaPi-III mRNA in kidney. At the 1st, 2nd, 4th, and 6th weeks, serum phosphorus and parathyroid hormone levels in HP group were significantly higher than those in LP and NP groups (P < 0.05). Serum calcium levels in the 3 groups showed no difference (P > 0.05). Comparing the expression of NaPi-IIa mRNA in HP group with LP and NP groups, NaPi-IIa mRNA expression was significantly reduced in HP group (P < 0.05), while NaPi-IIa mRNA expression in LP group began increasing at the 4th week (P < 0.05). At the 1st, 2nd, and 4th weeks, the expression of NaPi-III mRNA in HP, LP, and NP groups showed no clear differences (P > 0.05), while at the 6th week in HP group, NaPi-III mRNA expression was slightly increased compared to in LP and NP groups (P < 0.05). Hyperphosphatemia significantly affected NaPi-IIa and NaPi-III mRNA expression, and a factor promote an increase in intact parathyroid hormone independently of calcium.

[Effect of 2-methoxyestradiol combined with quercetin on prostate cancer in vitro].

OBJECTIVE: To detect the effects of quercetin (Que) combined with 2-methoxyestradiol (2-ME) on the proliferation of androgen-dependent LNCaP human prostate cancer cells line and androgen-independent PC-3 human prostate cancer cells line, and to evaluate the antitumor effects of different combos of the two drugs. METHODS: After LNCaP and PC-3 cells were treated with different concentration of quercetin (0, 3.125, 6.25, 12.5, 25, 50, 100, 200 µmol/L) or 2-ME (0, 0.312 5, 0.625, 1.25, 2.5, 5, 10 µmol/L) for 48 h, the inhibitory rates of cell growth were tested using trypan blue staining method respectively. Then the concentration-effect curves were drawn and IC(50) values were calculated. According to the fitted dose-effect curves and IC(50) values, appropriate concentrations of quercetin and 2-ME were selected to compose 16 different combos. Then cells were treated with different combos of Que and 2-ME for 48 h, and then the growth inhibitory rates of cell growth were detected. According to the equation and median-effect principle, the CI values of 16 different combos of Que and 2-ME were calculated to evaluate their antitumor effects. RESULTS: The inhibition rate of LNCaP or PC-3 cell growth treated with varying doses of quercetin or 2-ME alone showed a dose-dependent increase respectively. The IC(50) values of quercetin and 2-ME were 23.29 µmol/L and 1.89 µmol/L for LNCaP cells; and 22.12 µmol/L and 1.74 µmol/L for PC-3 cells respectively. After treated with 16 combos of Que (5, 10, 20, 40 µmol/L) and 2-ME (0.5, 1, 3, 5 µmol/L) for 48 h, for LNCaP cells, lower dose of Que (5 and 10 µmol/L) with higher dose of 2-ME (3 and 5 µmol/L) showed synergistic activity, whereas for PC-3 cells, besides the above combination of Que 10 µmol/L and 2-ME 3 µmol/L, higher dose of quercetin (20 and 40 µmol/L) with higher dose of 2-ME (3 and 5 µmol/L) also showed synergistic activity. CONCLUSIONS: Both quercetin and 2-methoxyestradiol could inhibit the growth of LNCaP and PC-3 human prostate cancer cells in a dose dependent manner. We confirmed that combinations of quercetin and 2-ME at appropriate concentrations have the potential for synergetic antiproliferative activity in vitro.