[Analysis of highly cited papers in Chinese Journal of Epidemiology from 2020 to 2023].

Objective: To analyze the characteristics of highly-cited papers in Chinese Journal of Epidemiology from 2020 to 2023, and provide a basis for subsequent paper solicitation and identify research hotspots. Methods: On December 9, 2023, the citation frequency of each paper in Chinese Journal of Epidemiology from 2020 to 2023 was obtained from China National Knowledge Infrastructure. The total citation frequency of each paper was sorted using Excel 2016 software, and papers with citation frequency ≥30 were extracted for analysis. The keywords of the papers and Contents in Brief were analyzed. Results: A total of 1 317 papers were included in the analysis, of which 389, 342, 308 and 278 papers were included from 2020 to 2023. The total citation frequency was 11 873, and all papers were cited with an average citation frequency of 9. The keywords with high citation frequency in the papers included 2019-nCoV, hypertension, colorectal tumor, hand-foot-mouth disease, hepatitis B. and the average frequency of citation were 162, 77, 62, 51 and 47, respectively. There were 15 highly cited Contents in Brief in total, 11 of which are vital Contents in Brief or unique Contents in Brief, including Response to COVID-19 Epidemic, China Kadoorie Biobank, Epidemiological Research on Infectious Diseases, Healthy Ageing, Colorectal Cancer Prevention and Control, Prevention and Control of Hepatitis B, Quality Assessment of Cancer Screening Guidelines and Consensus, The 40th Anniversary of Chinese Journal of Epidemiology, Expert Forum, Review, Standard-Protocol-Guide. The total citation frequency was 3 951, accounting for 72.6% (3 951/5 438) of highly cited papers. Conclusions: In the past four years, the highly cited papers of this journal mainly focused on the research field of emerging infectious diseases and chronic diseases. The response to the 2019-nCoV epidemic highlights the academic leading role. The effect of selecting and planning a topic, commissioning authors to write on given topics and making an arrangement in advance with a subject for contribution to vital Contents in Brief or unique Contents in Brief of this journal is pronounced, and the academic influence of the journal continues to improve.

[Laparoscopic versus open pelvic exenteration for locally advanced rectal cancer: analysis of short- and long-term effects].

Objective: To explore the feasibility, safety, and short- and long-term efficacy of laparoscopic pelvic exenteration (LPE) in treating locally advanced rectal cancer. Methods: The clinical data of 173 patients who had undergone pelvic exenteration (PE) for locally advanced rectal cancer that had been shown by preoperative imaging or intraoperative exploration to have invaded beyond the mesorectal excision plane and adjacent organs in the Cancer Hospital, Chinese Academy of Medical Sciences (n=64) and Peking University First Hospital (n=109) from 2010 January to 2021 December were collected retrospectively. Laparoscopic PE (LPE) had been performed on 82 of these patients and open PE (OPE) on 91. Short- and long-term outcomes (1-, 3-, and 5-year overall and disease-free survival and 1- and 3-year cumulative local recurrence rates) were compared between these groups. Results: The only statistically significant difference in baseline data between the two groups (P>0.05) was administration of neoadjuvant therapy. Compared with OPE, LPE had a significantly shorter operative time (319.3±129.3 minutes versus 417.3±155.0 minutes, t=4.531, P<0.001) and less intraoperative blood loss (175 [20-2000] ml vs. 500 [20-4500] ml, U=2206.500, P<0.001). The R0 resection rates were 98.8% and 94.5%, respectively (χ2=2.355, P=0.214). At 18.3% (15/82), and the incidence of perioperative complications was lower in the LPE group than in the OPE group (37.4% [34/91], χ2=7.727, P=0.005). The rates of surgical site infection were 7.3% (6/82) and 23.1% (21/91) in the LPE and OPE group, respectively (χ2=8.134, P=0.004). The rates of abdominal wound infection were 0 and 12.1% (11/91) (χ2=10.585, P=0.001), respectively, and of urinary tract infection 0 and 6.6% (6/91) (χ2=5.601, P=0.030), respectively. Postoperative hospital stay was shorter in the LPE than OPE group (12 [4-60] days vs. 15 [7-87] days, U=2498.000, P<0.001). The median follow-up time was 40 (2-88) months in the LPE group and 59 (1-130) months in the OPE group. The 1-, 3-, and 5-year overall survival rates were 91.3%, 76.0%, and 62.5%, respectively, in the LPE group, and 91.2%, 68.9%, and 57.6%, respectively, in the OPE group. The 1, 3, and 5-year disease-free survival rates were 82.8%, 64.9%, and 59.7%, respectively, in the LPE group and 76.9%, 57.8%, and 52.7%, respectively, in the OPE group. The 1- and 3-year cumulative local recurrence rates were 5.1% and 14.1%, respectively, in the LPE group and 8.0% and 15.1%, respectively, in the OPE group (both P>0.05). Conclusions: In locally advanced rectal cancer patients, LPE is associated with shorter operative time, less intraoperative blood loss, fewer perioperative complications, and shorter hospital stay compared with OPE. It is safe and feasible without compromising oncological effect.

[Analysis on academic quality and influence of Chinese Journal of Epidemiology, 2006-2019].

Objective: In recent years, the editorial board and editorial department of Chinese Journal of Epidemiology have taken a series of measures to further improve the academic quality and influence of the journal. This study analyzed the citation index of Chinese Journal of Epidemiology from 2006 to 2019, and evaluated the academic quality and influence of the journal. Methods: The total citation frequency, impact factor, annual index and other citation rate etc. of Chinese Journal of Epidemiology were extracted from Chinese S&T Journal Citation Report, 2006-2019 (Expanded Edition) and Chinese S&T Journal Citation Report, 2006-2019 (Natural Science) for the analysis on academic quality and influence of the journal. Results: From 2006 to 2019, there were 241-406 articles published in Chinese Journal of Epidemiology per year. The literature selection rate over the years ranged from 66% to 100%. The total expanded citation frequency of Chinese Journal of Epidemiology increased from 3 365 in 2006 to 7 817 in 2019, and the total core citation frequency increased from 1 875 in 2006 to 5 055 in 2019 with slight fluctuation. The expanded impact factor increased from 1.566 in 2006 to 2.799 in 2019. The core impact factor increased from 0.904 in 2006 to 1.842 in 2019. The expanded annual index rose from 0.224 in 2006 to 0.741 in 2019. The core annual index rose from 0.170 in 2006 to 0.602 in 2019. Conclusion: The academic quality and influence of Chinese Journal of Epidemiology has been improved gradually and its ability to focus on hot spots and report new academic achievement has been further strengthened in recent years.

[Thirty years' changes of the strategy of lateral lymph node dissection in low rectal cancer: treatment experience and prognostic analysis of 289 cases in one single center].

Objective: The surgical indications, resection extent and management principle of lateral lymph node dissection (LLND) in lower rectal cancer have been controversial between Eastern and Western countries. This study aims to provide a theoretical basis for the rational implementation of LLND by reviewing the changes of LLND strategy over the past 30 years in a single-center, and analyzing prognostic factors for the survival outcomes of patients with lateral lymph node metastasis (LLNM). Methods: A retrospective observational study was performed. Clinical data of 289 patients with rectal cancer who received LLND at the Department of General Surgery of Peking University First Hospital from 1990 to 2019 were collected. Patients were divided into three groups based on decades. There were 89 cases in 1990-1999 group, 92 cases in the 2000-2009 group, and 108 cases in the 2010-2019 group. Data analyzed: (1) patient baseline data; (2) surgery and postoperative recovery; (3) lateral lymph node dissection; (4) postoperative survival and prognosis of patients with positive lateral lymph nodes. The surgical methods and pathological results of LLND were compared between groups, and the prognostic risk factors of patients with LLNM were analyzed. Results: A total of 289 patients underwent radical resection with LLND' accounting for 6.3% of the 4542 patients with rectal cancer during the same period in our hospital. Except decade-by-decade increase in tumors with distance from anal verge ≤ 7 cm, the proportion of ulcerated tumors, and the proportion of neoadjuvant radiochemotherapy, the differences in other baseline data were not statistically significant among 3 decade groups (all P>0.05). The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2490), χ(2)=40.159, P<0.001]. The proportion of laparoscopic surgery and unilateral LLND increased, while the mean operative time, intraoperative blood loss, surgical complications above grade III and postoperative hospital stay decreased decade by decade. These 289 patients completed a total of 483 lateral dissections, including 95 cases of the unilateral dissection and 194 cases of the bilateral dissection. The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2510), P<0.001]. The median number of dissected lymph nodes in the internal iliac artery and obturator regions increased (2 vs. 3 vs. 3, P<0.001), but those in the common iliac and external iliac regions decreased significantly (4 vs. 3 vs. 2, P=0.014). A total of 71 patients with LLNM were identified. The rate of LLNM in the 2010-2019 group was significantly higher than that in the previous two groups [37.0% (40/108) vs. 16.9% (15/89) vs. 17.4% (16/92), P=0.001]. The patients with LLNM showed a poorer overall survival (OS) and disease-free survival (DFS) compared with negative lateral lymph nodes (P<0.001). There were statistically significant differences in 5-year OS rate (30.9% vs. 27.2% vs. 0, P=0.028) and 5-year DFS rate (28.3% vs. 16.0% vs. 0, P=0.038) among patients with only internal iliac lymph node metastasis, patients with only obturator lymph node metastasis, and patients with external iliac or common iliac lymph node metastasis. Multivariate analysis of prognostic factors showed that external iliac or common iliac lymph node metastasis was an independent risk factor for OS (HR=1.649, 95%CI: 1.087-2.501) and DFS (HR=1.714, 95%CI: 1.173-2.504) in patients with LLNM (all P<0.05) . The OS and DFS were not significant different in patients with LLNM among 3 decade groups. Conclusions: In the past decade, the proportion of LLND in rectal cancer has decreased significantly. However, LLNM rate has been significantly increased due to preoperative imaging assessments focusing on suspicious LLNM without compromising the survival. Internal iliac artery and obturator lymph nodes can be regarded as regional lymph nodes with a satisfactory prognosis after LLND. For suspected external iliac or common iliac lymph node metastasis, the significance of LLND remains to be further evaluated.

Impact of socio-economic deprivation on endometrial cancer survival in the North West of England: a prospective database analysis.

OBJECTIVE: To assess the impact of socio-economic deprivation on endometrial cancer survival. DESIGN: Single-centre prospective database study. SETTING: North West England. POPULATION: Women with endometrial cancer treated between 2010 and 2015. METHODS: Areal-level socio-economic status, using the English indices of multiple deprivation from residential postcodes, was analysed in relation to survival using Kaplan-Meier estimation and multivariable Cox regression. MAIN OUTCOME MEASURES: Overall survival, cancer-specific survival and patterns and rates of recurrence. RESULTS: A total of 539 women, with a median age of 66 years (interquartile range, IQR 56-73 years) and a body mass index (BMI) of 32 kg/m2 (IQR 26-39 kg/m2 ), were included in the analysis. Women in the most deprived social group were younger (median 64 years, IQR 55-72 years) and more obese (median 34 kg/m2 , IQR 28-42 kg/m2 ) than women in the least deprived group (median age 68 years, IQR 60-74 years; BMI 29 kg/m2 , IQR 25-36 kg/m2 ; P = 0.002 and <0.001, respectively). There were no differences in endometrial cancer type, stage or grade between social groups. There was no difference in recurrence rates, however, women in the middle and most deprived social groups were more likely to present with distant/metastatic recurrence (80.6 and 79.2%, respectively) than women in the least deprived group (43.5%, P < 0.001). Women in the middle and most deprived groups had a two-fold (adjusted hazard ratio, HR = 2.00, 95% CI 1.07-3.73, P = 0.030) and 53% (adjusted HR = 1.53, 95% CI 0.77-3.04, P = 0.221) increase in cancer-specific mortality compared with women in the least deprived group. There were no differences in overall survival. CONCLUSIONS: We found that socio-economically deprived women with endometrial cancer were more likely to develop fatal recurrence. Larger studies are needed to confirm these findings and to identify modifiable contributing factors. TWEETABLE ABSTRACT: Socio-economic deprivation is linked to an increased risk of death from endometrial cancer in the North West of England.

[Analysis on risk factors of the degree of radical resection and prognosis of patients with locally recurrent rectal cancer].

Objective: To evaluate the factors affecting the degree of radical resection and the prognosis of patients with locally recurrent rectal cancer (LRRC). Methods: A retrospective case-control study was performed. Clinical data of 111 patients with LRRC undergoing operation at the General Surgery Department of Peking University First Hospital from January 2009 to August 2019 were analyzed retrospectively. The "Peking University First Hospital F typing" was performed according to the preoperative images of the pelvic involvement. The pelvis was assigned into four directions: the front wall, lateral sides of the pelvic wall and the sacrum. According to the degree of pelvic wall involvement, F typing included F0 type (no involvement of the pelvic wall, the cancer only involved the adjacent organs or invaded conteriorly the urinary tract, genital organs or small intestine), F1 type (cancer involved the pelvic wall in one direction, such as the sacrum, or one side of the pelvic wall), F2 type (cancer involved the pelvic wall in two directions) and F3 type (cancer involved the pelvic wall in three directions). Case inclusion criteria: (1) LRRC was confirmed by imaging and pathological examination of samples (puncture or endoscopic biopsy); (2) complete clinical and follow-up data; (3) informed consent of patient. Those with dysfunction of heart, lung, etc., intolerance of operation, F3 type indicated by image, and distant metastasis were excluded. The degree of radical resection was evaluated according to the postoperative pathological results. Patients were followed up every 12 months and related examinations were arranged. The univariate analysis of radical resection was performed by χ(2) test, and the multivariate analysis was performed by logistic methods. The survival rate was calculated by Kaplan-Meier method and the survival curve was drawn. The survival rate was compared by log-rank test. Cox proportional hazards model was used to analyze the factors affecting the prognosis of patients with LRRC. Results: A total of 111 patients were included in this study. Of 111 patients, 59 were male and 52 were female; recurrent age of 36 cases was ≥ 65 years old; CEA level of 48 cases was ≥15 µg/L. According to the "Peking University First Hospital F typing", 70 cases were F0 type, 38 F1 type and 3 F2 type. Surgical procedures were abdominoperineal resection (n=28), posterior pelvic exenteration (n=32), and total pelvic exenteration (n=51, including 1 case of TPE combined with sacrectomy). According to the postoperative pathological results, R0, R1 and R2 resections were 83, 20 and 8 cases, respectively. Univariate analysis showed that the degree of radical resection was associated with the secondary surgical procedure, F typing and lymph node metastasis (all P<0.05). Multivariate analysis showed that F typing (F1-F2) was an independent risk factor for non- R0 resection (OR=37.256, 95%CI:8.572 to 161.912, P<0.001). The morbidity of operative complications was 22.5% (25/111); the perioperative mortality was 1.8% (2/111); the local recurrence rate after the second operation was 37.8% (42/111). The 3- and 5-year overall survival rates were 41.2% and 21.9% respectively. The 3-year survival rates of patients with and without postoperative chemotherapy were 52.7% and 32.4% respectively (P=0.005). The 3-year survival rates of patients with lower (<15 µg/L) and higher CEA level (≥15 µg/L) were 52.9% and 24.3% respectively (P<0.001). The 3-year survival rates of patients with R0, R1 and R2 resection were 49.8%, 21.3% and 8.5% respectively (P=0.002). The 3-year survival rates of patients with F0, F1 and F2 type were 52.7%, 22.0% and 0 respectively (P<0.001). Cox analysis confirmed that the degree of radical resection (HR=2.088, 95%CI:1.095 to 3.979, P=0.025), the CEA level before the secondary operation (HR=1.857, 95%CI:1.157 to 2.980, P=0.010) and postoperative chemotherapy (HR=1.826, 95%CI:1.137 to 2.934, P=0.013) were independent factors affecting the prognosis. Conclusions: The indication of LRRC surgical treatments must be strictly limited. Evaluation of the fixation site to the pelvic wall is helpful for improving the rate of R0 resection. Lower preoperative CEA level, radical resection and postoperative chemotherapy are protective factors of prolonged overall survival time of patients with LRRC.

[Mechanism of cross talk between tissue factor/active coagulation factor VII and epidermal growth factor receptor signalings in colon cancer cells in culture].

OBJECTIVE: To preliminarily verify the cross talk between tissue factor/active coagulation factor VII (TF/FVIIa) and epidermal growth factor receptor (EGFR) pathways in human colon cancer cells in culture. METHODS: FVIIa was treated to HT-29 (KRAS-wild type) and LoVo (KRAS-mutant) colon cancer cells to activate TF/FVIIa pathway, qRT-PCR and Western blot were used to detect the expressions of amphiregulin (AREG) and epiregulin (EREG), ligands of EGFR on mRNA and protein levels, respectively. After knocking down expression of TF by TF-targeted siRNA transfection, FVIIa was treated and mRNA expressions of AREG and EREG were detected to see whether the FVIIa-induced effects were dependent on TF. Expressions of mRNA of TF and FVII were detected by qRT-PCR following the activation of EGFR pathway by treatment with epidermal growth factor (EGF) to HT-29 and LoVo cells. RESULTS: After TF/FVIIa pathway was activated, for HT-29 cells, expressions of AREG (on mRNA level) and EREG (both on mRNA and protein level) were significantly down-regulated versus those of control group, gene expressions of AREG and EREG were 0.55±0.09 vs.0.99 ±0.09, 0.67±0.10 vs.1.02±0.02, protein expressions of EREG were 0.54±0.09 vs.1.04±0.13, all P<0.05. For LoVo cells, expressions of AREG (both on mRNA and protein level) and EREG (on protein level) were significantly up-regulated versus those of control group, gene expression of AREG were 1.87±0.39 vs. 0.93±0.23, protein expressions of AREG and EREG were 3.09±0.73 vs.1.11±0.21, 1.53±0.19 vs.0.97±0.23, all P<0.05. The regulating effect of AREG and EREG mRNA expression by FVIIa in HT-29 and LoVo cells could both be partly blocked by knocking down TF expression. For HT-29 cells, activation of EGFR pathway induced no significant TF mRNA expression, FVII mRNA expression was not detected. However,for LoVo cells, activation of EGFR pathway induced significantly higher mRNA expressions of both TF and FVII, expressions were 1.53±0.23 vs.1.00±0.23, 53.20±6.08 vs.1.00±0.15, all P<0.05. CONCLUSION: In colon cancer cell LoVo, when activated, TF/FVIIa pathway and EGFR pathway could interact through upregulating the other pathway's effectors, and mutant KRAS might play a critical role in the two pathways' cross talk.

[Effects of NPM1 gene expression on acute myeloid leukemia cell lines and its mechanism].

Objective: To investigate the impact and mechanism of NPM1 gene expression on acute myeloid leukemia (AML) cell lines. Methods: Human AML cell line U937 and HL-60 cells were transfected with NPM1 plasmid to establish stable clones, and the high NPM1 protein expression (NPM1(hi)) clones were screened by Western blot. The cell proliferation was assayed by methylthiazolyl tetrazolium bromide (MTT) , cell cycle and cell apoptosis by flow cytometric, cell colony formation by microscope count, the molecular pathways related to cell cycle by Western blot. The expression of NPM1 gene in primary AML bone marrow mononuclear cells (BMMC) was investigated by RQ-PCR. Results: ①The proliferation of NPM1(hi) U937 and HL-60 cells was similar with that of control cells (4.68±1.28 vs 3.89±0.81, 3.34±0.37 vs 2.68±0.29, P>0.05) . ②The percentage of S phase in NPM1(hi) U937 and HL-60 cells was higher than that in control cells[ (50.22±3.42) % vs (39.78±3.80) %, (59.01±3.27) % vs (43.94±2.08) %, P<0.05]. ③The anti-apoptosis capacity and colony formation abilities of NPM1(hi) U937 cells increased than that of control cells[ (68.8±10.2) % vs (48.7±3.22) %, and (772.7±24.0) vs (652.3±16.5) , P<0.05], but the above abilities of NPM1(hi) HL60 cells were similar with that of control cells. ④ The expressions of CDK4, Cyclin D1, Cyclin D2 and Cyclin E in NPM1(hi) leukemia cells were higher than that of control cells, but the expression of Cyclin D3 was lower. ⑤The NPM1 expression levels in AML patients with favorable cytogenetic prognosis were lower than that of patients with intermediate prognosis. Conclusions: NPM1 protein could promote more cells to enter S phase, enhance the ability of antiapoptosis and colony formation in AML cell lines. The quantitative level of NPM1 may predict the cytogenetic risk of AML patients.

[Study of the effects and mechanism of all-trans retinoic acid on leukemic cell line U937 cells with NPM1 mutation].

Objective: To investigate the effect and mechanism of all-trans retinoic acid (ATRA) on leukemic cell line U937 cells with NPM1 mutation. Methods: Human acute myeloid leukemia cell line U937 was explored, NPM1 mutated (A type) plasmids were transfected into U937 to form stable clones A1 and A2, which were identified by Western blot and Co-immunoprecipitation. The cell proliferation was measured by methylthiazolyl tetrazolium bromide (MTT) ; cell cycle and cell apoptosis were explored by flow cytometric; cell colony formation was measured by microscope count, the molecular pathways related to cell proliferation were measured by Western blot. Results: ①The cell proliferations of mutant A1 and A2 were inhibited significantly by 52.6% and 35.8% (P<0.05) , respectively under ATRA exposure. ②The percentages of G(0)/G(1) stage of mutant A1 and A2 increased by 20.1% and 35.8%, respectively under ATRA exposure. ③All the U937 leukemic cells were inhibited under ATRA exposure; the decreased percentages of vector, wild-type and mutant NPM1 cells were 32.7%, 57.9% and 90.9% respectively. ④p-ERK decreased obviously after ATRA exposure in NPM1 mutated leukemic cells. ⑤More mutant NPM1 cells inclined to apoptosis under the exposure of ATRA and cytotoxic drugs than cytotoxic drugs alone, meanwhile more cells apoptosis occurred when ATRA was administrated after cytotoxic drugs exposure. Conclusions: ATRA could inhibit cell proliferation and colony formation, blocked the cell cycle in the G(0)/G(1) stage accompanied by the significant reduction of p-ERK in U937 leukemic cells with NPM1 mutation. Besides, ATRA could synergize with drugs to suppress the leukemic cells survival more effectively when ATRA was administered after the cytotoxic drugs exposure in U937 leukemic cells with NPM1 mutation.

[Application of imatinib in BCR- ABL positive acute lymphoblastic leukemia treatment in the real world].

Objective: To explore the efficacy and prognostic factors of imatinib(IM)combined with chemotherapy for BCR-ABL gene positive acute lymphoblastic leukemia(ALL). Methods: A total of 209 BCR-ABL+ALL patients treated with imatinib plus chemotherapy from April 2003 to August 2015 were enrolled in the study, and 106 patients underwent hematopoietic stem cell transplantation(HSCT). Results: The complete remission(CR)rate was 97.9% in newly diagnosed patients. WBC≥100×109/L at diagnosis was a poor factor for overall survival(OS)(P=0.043). Without HSCT, not achieved CR within 4 weeks in the first cycle induction chemotherapy and complete molecular remission(CMR)not achieved during the treatment were adverse factors for OS(P<0.001, P=0.009, P<0.001, respectively), as well as for relapse free survival(RFS)(P<0.001, <0.001 and <0.001, respectively). Of the 106 patients who underwent allo-HSCT or auto-HSCT, there was no statistically significant difference on the OS and RFS. There was no significant difference on OS in patients treated with imatinib or not in the induction chemotherapy, but the former showed higher 5-year RFS rate(37.0% vs 24.0%, P=0.005). The survival of the patients who took tyrosine kinase inhibitors(TKIs)regularly and continuously was the best(40 patients changed to other TKI due to relapse/unsatisfactory decrease in transcription level/occurrence of mutation), followed by those who interrupted TKIs during the bone marrow suppression, those who took TKIs irregularly the worst. The 5- year OS rates among three groups were 46.0%, 28.0% and 17.0%, respectively(P=0.004). The 5- year EFS rates among three groups were 38.0%, 28.0% and 17.0%, respectively(P<0.001). Conclusion: TKIs plus chemotherapy followed by HSCT improved the prognosis of the patients with BCR-ABL+ALL patients. It is important to administer TKIs regularly and continuously to improve the outcome of BCR-ABL+ALL patients.

Stimulation of contractions in pregnant human myometrium is associated with 5-HT3 receptors.

BACKGROUND: Serotonin (5-HT) is known to play an important role in regulating uterine contractions. However, the specific receptors involved have not been well characterized. We evaluated whether 5-HT3 receptors exist in human myometrium, and their effects on myometrial contractility when stimulated by a 5-HT3 agonist. METHODS: Four tissue samples taken from patients undergoing hysterectomy (n=2) and elective cesarean delivery (n=2) were used to detect expression of 5-HT3 receptors on the myometrium using western blotting. For isometric tension measurement, another 12 myometrial strips obtained from patients undergoing elective cesarean delivery were randomly divided into a control group (Group CON) and an RS56812 group (Group RG). In increasing doses from 10-7M to 10-4M, RS56812, a 5-HT3 receptor agonist, was used to investigate the contractile effects after bonding to the 5-HT3 receptor, following which the effects of granisetron were assessed. Amplitude, interval and duration of myometrial contractions were recorded. RESULTS: Proteins with a molecular mass of 55kDa, consistent with 5-HT3 receptors, were detected both on non-pregnant and late-pregnant human uteri. RS56812 increased the contractile amplitude at concentrations of 10-6M, 10-5M and 10-4M, achieving maximum effect at 10-5M. A prolonged contractile interval was detected at the concentration of 10-4M. However, RS56812 showed no significant effect on contraction duration. Granisetron did not reverse the contractile effects induced by RS56812. CONCLUSION: 5-HT3 receptors are expressed on non-pregnant and pregnant uteri. RS56812 enhanced myometrial contractions, but this was not affected by granisetron, the mechanism of which requires further investigation.

Curvature measurement of human bilateral cochleae.

OBJECTIVE: This study aimed to characterise the geometry of the human bilateral spiral cochlea by measuring curvature and length. METHOD: Eight subjects were recruited in this study. Magnetic resonance imaging was used to visualise the right and left cochlea. Visualisation of the cochlear spiral was enhanced by T2 weighting and further processing of the raw images. The spirals were divided into three segments: the basal turn, the middle turn and the apex turn. The length and curvature of each segment were non-invasively measured. RESULTS: The mean left and right cochlear lengths were 3.11 cm and 3.95 cm, respectively. The measured lengths of the cochlear spiral are consistent with data in the literature derived from anatomical dissections. Overall, the apex turn segment of the cochlea had the greatest degree of curvature (p < 0.05). The mean apex turn segment curvatures for left and right cochleae were 9.65 cm(-1) and 10.09 cm(-1), respectively. CONCLUSION: A detailed description of the cochlear spiral is provided, using measurements of curvature and length. These data will provide a valuable reference in the development of cochlear implantation procedures for minimising the potential damage during implantation.

Comparative proteomic changes of differentially expressed whey proteins in clinical mastitis and healthy yak cows.

Under the traditional grazing system on the Qinghai-Tibetan Plateau, the amount of milk in domesticated yak (Bos grunniens) with clinical mastitis decreases and the milk composition is altered. To understand the mechanisms of mammary gland secreted milk and disease infection, changes in the protein composition of milk during clinical mastitis were investigated using a proteomic approach. Milk whey from yak with clinical mastitis was compared to whey from healthy animals with two-dimensional gel electrophoresis using a mass spectrometer. Thirteen protein spots were identified to be four differentially expressed proteins. Increases in the concentrations of proteins of blood serum origin, including lactoferrin, were identified in mastitic whey compared to normal whey, while concentrations of the major whey proteins, casocidin-I, a-lactalbumin, and b-lactoglobulin, were downregulated in mastitic whey. These results indicated significant differences in protein expression between healthy yaks and those with clinical mastitis, and they may provide valuable information for finding new regulation markers and potential protein targets for the treatment of mastitis.

Differentiation of tumefactive demyelinating lesions from high-grade gliomas with the use of diffusion tensor imaging.

BACKGROUND AND PURPOSE: TDLs may be indistinguishable from high-grade gliomas on conventional MR imaging. The role of DTI in differentiating TDLs from high-grade gliomas is not clear, and quantitative comparison between the 2 has not been reported. Here we aimed to differentiate TDLs from high-grade gliomas by using DTI. MATERIALS AND METHODS: DTI was performed in 8 TDLs and 13 high-grade gliomas. The presence of 3 findings (ie, intralesional hyperintensities on the FA map, restricted diffusion in the lesion periphery, and a perilesional hyperintense FA rim) was assessed by visual inspection. The FA and MD values were measured in the central nonenhancing portion, peripheral enhancing portion, and perilesional edema for each lesion and compared between the 2 groups respectively. RESULTS: TDLs had a significantly higher incidence of intralesional hyperintensities on FA maps (P = .049) but a lower incidence of a perilesional hyperintense FA rim (P < .001), compared with those of high-grade gliomas on visual inspection. TDLs had significantly higher FA (P = .004) and lower MD (P = .001) values in the peripheral enhancing portions of the lesions compared with those of high-grade gliomas. In perilesional edema, FA values were significantly higher in high-grade gliomas (P = .001). CONCLUSIONS: DTI is helpful in differentiating TDLs from high-grade gliomas by using visual inspection and quantitative analysis.

The efficacy of levonorgestrel intrauterine systems for endometrial protection: a systematic review.

BACKGROUND: Oral progestogens are commonly used for endometrial protection in women at higher risk of developing endometrial abnormality. Long-term intrauterine progestogens may offer an attractive alternative to oral therapy. OBJECTIVE: To review the evidence regarding the efficacy of intrauterine levonorgestrel-releasing systems (LNG-IUS) in preventing endometrial pathology in high-risk women. METHOD: Searches were made of the Cochrane Central Register of Controlled Trials, UK National Research Register (NRR) Archive, Current Controlled Trials, MEDLINE, EMBASE and CINAHL. The selection criteria were randomized, controlled trials (RCTs) comparing LNG-IUS with no treatment, placebo or other hormonal therapy in adult females. Where no RCTs were available, prospective cohort studies were analyzed. Data was extracted using a standardized data collection form. Meta-analysis was performed using RevMan software. RESULTS: There were six RCTs that investigated LNG-IUS in women using estrogen replacement therapy (ERT). LNG-IUS was at least as effective as other routes of progestogen administration. Only two studies investigated LNG-IUS as treatment for endometrial hyperplasia. Hyperplasia without atypia regressed in all women treated with LNG-IUS. In three studies of LNG-IUS in tamoxifen users, LNG-IUS was associated with reduced risk of endometrial polyps (Peto odds ratio (OR) 0.28; 95% confidence interval (CI) 0.15-0.55) and hyperplasia (Peto OR 0.14; 95% CI 0.02-0.80). CONCLUSIONS: LNG-IUS counters endometrial proliferation and causes regression of and prevents endometrial hyperplasia in selected groups of women. There is, however, insufficient evidence to recommend LNG-IUS as the treatment of choice for hyperplasia and no evidence to adequately support its use as chemoprevention in women with hereditary non-polyposis colorectal cancer syndrome or obesity.

Differentiation of brain abscesses from necrotic glioblastomas and cystic metastatic brain tumors with diffusion tensor imaging.

BACKGROUND AND PURPOSE: The differentiation of abscesses from glioblastomas and metastases may not always be possible on the basis of DWI. Our hypothesis was that differences in diffusion properties as detected by DTI allow differentiation of abscess from glioblastomas and metastasis. Furthermore, diagnostic performance of tensor metrics quantifying anisotropy or tensor shapes is better than that of ADC in measuring mean diffusivity for this purpose. MATERIALS AND METHODS: DTI was performed in 15 abscesses, 15 necrotic glioblastomas, and 26 cystic metastases. In each lesion, manually segmented into 4 regions of interest (ie, cystic cavity, enhancing rim, and immediate [edema most adjacent to the enhancing rim] and distant zones of edema), FA, ADC, C(l), C(p), and C(s) values were measured and statistically compared among groups and evaluated with ROC curve analysis. The presence of a hyperintense FA rim (a rim of edematous tissue that was hyperintense on the FA map) was assessed visually. RESULTS: Abscess was significantly different from glioblastoma for all tensor metrics measured in the cystic cavity and immediate zone of edema and for all except C(l) in the enhancing rim. Abscess was significantly different from metastasis for all tensor metrics measured in the cystic cavity and enhancing rim and for FA, ADC, and C(l) in immediate zone of edema. The incidence of a hyperintense FA rim was significantly higher in glioblastoma and metastasis compared with abscess. The 3 tensor metrics with the highest performance in differentiating abscess from glioblastoma and metastasis were FA, C(l), and C(s) of the cystic cavity. CONCLUSIONS: DTI is able to differentiate abscess from glioblastoma and metastasis. FA, C(l), and C(s) outperformed ADC in diagnostic performance comparisons.

The mutL mutation in Pseudomonas aeruginosa isolates reveals multidrug-resistant traits and possible evolutionary trends.

To evaluate the genetic differences and possible evolutionary trends of clinical multidrug-resistant (MDR) strains, Pseudomonas aeruginosa isolates were characterized by pulsed-field gel electrophoresis (PFGE) and evolutionary distances were estimated. A total of 85.7% of the P. aeruginosa isolates were MDR strains. Strains with the PFGE pattern A predominated; all were susceptible to amikacin and cefepime but resistant to levofloxacin and meropenem (except strain PA45 which was sensitive to meropenem). PFGE pattern H or P strains exhibited resistance to six to eight different antibiotics. PFGE pattern I or J strains were susceptible to all antibiotics tested. Two imperfect six base-pair tandem repeats, CTGGCG and CTGGCC, were found in the mutL gene. In conclusion, MDR characteristics and PFGE profiles were clearly correlated with the mutL phylogenetic tree. This indicates that mutations in mutL might contribute to genetic stability in adaptation by changing the MDR traits. Phylogenetic analysis of mutL revealed the MDR relatedness of P. aeruginosa strains.

Significant temporal evolution of diffusion anisotropy for evaluating early response to radiosurgery in patients with vestibular schwannoma: findings from functional diffusion maps.

BACKGROUND AND PURPOSE: Outcome evaluation in clinical oncology is conventionally based on long-term volumetric changes in the tumor size. The purpose of this study was to prospectively investigate the usefulness of fDMs in incorporating anisotropic diffusion in the evaluation of early response after radiosurgery in patients with vestibular schwannoma. MATERIALS AND METHODS: The MD, FA, and IVDC were calculated by using simple averaging methods and fDMs. Six patients with vestibular schwannoma treated with stereotactic radiosurgery underwent longitudinal DTI studies on a 3T MR imaging scanner (maximum follow-up, 6 months). Posttreatment DTI data were spatially coregistered with pretreatment scans. RESULTS: Tumors did not change significantly in size until 6 months after treatment. Diffusion indices changed significantly during the study period. There was a transient decrease in averaged MD followed by a significant increase. IVDC showed an opposite behavior compared with MD. FA decreased continuously throughout the study period. Functional diffusion maps showed a heterogeneous response of tumors to treatment, thereby providing complementary information to simple averaged values. CONCLUSIONS: DTI allows early detection of therapeutic-induced changes in patients with vestibular schwannoma. Functional diffusion maps incorporating anisotropic diffusion may aid in assessing the heterogeneity of the therapeutic response in this patient group.