Role of blood markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection / 中华外科杂志

Objective: To investigate the value of inflammation,coagulation and nutrition markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection(PJI). Methods: A retrospective study was conducted on 70 patients who undertook prosthesis removal and antibiotic-loaded bone cement spacer implantation due to PJI from June 2016 to October 2020 in the Department of Orthopedics,Henan Provincial People's Hospital. There were 28 males and 42 females,aged (65.5±11.9) years (range: 37 to 88 years). Patients were divided into two groups as the successful group and the failed group depended on whether reinfection occurred after prosthesis removal and antibiotic-loaded bone cement spacer implantation at the last follow up. Patient demographics,laboratory values (C-reactive protein (CRP),erythrocyte sedimentation rate (ESR),ESR and CRP ratio (ESR/CRP),white blood cell count(WBC),platelet count(PLT),hemoglobin(HB),total lymphocyte count(TLC),albumin、fibrinogen(FIB),CRP and albumin ratio (CAR),prognostic nutritional index(PNI)),and reinfection rates were assessed. Comparison between groups was conducted by the independent sample t test or χ2test. Receiver operating characteristic (ROC) curve was plotted,and the area under the curve (AUC),optimal diagnostic threshold,sensitivity,and specificity were analyzed to predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation. Results: All patients were followed up for at least two years,and the follow-up time was (38.4±15.2) months (range: 24 to 66 months). Fifteen patients suffered failure after prosthesis removal and antibiotic-loaded bone cement spacer implantation,while the other 55 patients succeeded. The overall failure rate of prosthesis removal and antibiotic-loaded bone cement spacer implantation in PJI treatment was 21.4%. Level of preoperative CRP ((35.9±16.2)mg/L),PLT ((280.0±104.0)×109/L) and CAR (1.3±0.8) in successful group were lower than CRP ((71.7±47.3)mg/L),PLT ((364.7±119.3)×109/L) and CAR (2.5±2.0) in failed group (all P<0.05).Whereas,level of preoperative ESR/CRP (3.3±3.1), Albumin ((35.3±5.2)g/L) and PNI (43.6±6.2) in successful group were higher than ESR/CRP (1.6±1.4),Albumin ((31.3±4.8)g/L) and PNI (39.2±15.1) in failed group (all P<0.05). AUC of ROC curve,optimal threshold value,sensitivity and specificity of CRP,ESR/CRP, PLT, Albumin,CAR and PNI for the predicting failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation were 0.776(95%CI:0.660 to 0.867),35.4 mg/L,86.7%,67.3%;0.725(95%CI:0.605 to 0.825),1.0,60.0%,78.2%;0.713(95%CI:0.593 to 0.815),253,93.3%,47.3%;0.721(95%CI:0.601 to 0.822),35.7,93.3%,49.1%;0.772(95%CI:0.656 to 0.863),1.1,86.7%,67.3%;0.706(95%CI:0.585 to 0.809),45.7,100%,41.8% respectively. Conclusion: In patients with PJI,CRP>35.4,ESR/CRP≤1.0 and CAR>1.1 could predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation.

Primary pulmonary NUT carcinoma: a clinicopathological analysis of seven cases / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics of primary pulmonary NUT carcinoma. Methods: A total of 7 cases of primary pulmonary NUT carcinoma were collected from Fujian Provincial Hospital (n=5), Fuzhou Taijiang Hospital (n=1) and Binzhou City People's Hospital of Shandong Province (n=1) from January 2021 to April 2023. The clinical, histopathological, and immunohistochemical features were analyzed, and NUT rearrangement were detected by fluorescence in situ hybridization (FISH) with break-apart probes. Results: Seven cases were all male with age ranging from 32 to 73 years. The main clinical manifestations were cough, expectoration and chest tightness. Microscopically, NUT carcinoma was composed of monotonous proliferation of primitive-appearing small-to-medium round cells, with few eosinophilic cytoplasm, arranged in solid sheets, nests or clusters. Abrupt keratinization was typically observed in 4 cases (4/7), with high mitotic activities and necrosis. Immunohistochemistry (IHC) showed that the tumors were positive for NUT (7/7), CK7 (4/4), CK5/6 (5/6), p40 (6/7). Ki-67 index were 30%-80%. NUT gene segregation (7/7) was detected by FISH break probes. Conclusions: Primary pulmonary NUT carcinoma is rare and highly malignant. Diagnosis depends on histopathology and IHC, with molecular detection as an adjunct for diagnosis. Pathologists should be aware of the clinicopathological characteristics to avoid misdiagnosis.

Evaluation of at-home methods for N95 filtering facepiece respirator decontamination

N95 filtering facepiece respirators (FFRs) are essential for the protection of healthcare professionals and other high-risk groups against Coronavirus Disease of 2019 (COVID-19). In response to shortages in FFRs during the ongoing COVID-19 pandemic, the Food and Drug Administration issued an Emergency Use Authorization permitting FFR decontamination and reuse. However, although industrial decontamination services are available at some large institutions, FFR decontamination is not widely accessible. To be effective, FFR decontamination must 1) inactivate the virus; 2) preserve FFR integrity, specifically fit and filtering capability; and 3) be non-toxic and safe. Here we identify and test at-home heat-based methods for FFR decontamination that meet these requirements using common household appliances. Our results identify potential protocols for simple and accessible FFR decontamination, while also highlighting unsuitable methods that may jeopardize FFR integrity. One sentence summarySurvey of at-home methods for N95 respirator decontamination using heat and evaluation of their effects on N95 respirator integrity.

Application of computer-assisted system in surgery for pediatric solid pseudopapillary tumor / 中华实用儿科临床杂志

Objective@#To explore the value of Hisense computer-assisted surgical systems (CAS) for precise surgery of pediatric solid pseudopapillary tumor.@*Methods@#A total of 5 cases with pancreatic solid pseudopapi-llary tumor who were admitted at the Affiliated Hospital of Qingdao University from June 2015 to September 2018 were adopting.Upper abdominal 64-slice dynamic enhanced computed tomography (CT) scan was performed.3D models were created by computer-assisted surgery systems.Based on 3D model, surgical planning, preoperative simulated tumor resection, intraoperative assisted guidance were performed.Operation time, intraoperative blood loss volume, blood transfusion rate were analyzed.@*Results@#Hisense CAS three-dimensional reconstruction could clearly show the adjacent relationship between pancreas, tumor and peripheral vascular organs.According to the preoperative virtual resection, pancreatic tumor resection was more accurate.Postoperative pathological results were solid pseudopapillary tumor of the pancreas.Among them, 2 tumors were located in the head of the pancreas, 1 case was located in the pancreatic neck, and 2 cases in the tail of the pancreas.The operation time was 150-360 min, with an average of 279 min.The average intraoperative blood loss was 40 mL, of which the minimum amount of bleeding was 5 mL, and the blood transfusion rate was 40%(2/5 cases). Surgical tumor removal was achieved successfully in 5 cases.All children were followed up for 6 months to 3 years, and no recurrence or metastasis was observed.@*Conclusions@#Three-dimensional reconstruction of computer-assisted surgery system can clearly show the adjacent relationship between tumor and surroun-ding vascular organs, and help to make the best surgical plan before surgery to improve the accuracy and safety of the operation.

Echocardiographic evaluation of left ventricular diastolic function in patients with diastolic heart failure and comparative study of real‐time cardiac catheterization / 中华超声影像学杂志

Objective To evaluate the left ventricular diastolic function of patients with normal left ventricular ejection fraction ( LVEF) by echocardiography and real‐time cardiac catheter measurement ,and improve the accuracy and reliability of echocardiographic diagnosis . Methods One hundred and twenty patients with know n or suspected coronary artery disease w ho underwent coronary angiography and left ventricular catheterization were prospectively selected from July 2017 to January 2018 in the Affiliated Hospital of Jiangsu University . According to the left ventricular end diastolic pressure ( LVEDP) real‐time measurement ,the patients were divided into groups of LVEDP ≤15 mm Hg ( 43 cases ) and LVEDP ＞ 15 mm Hg ( 77 cases) . General data were compared and the difference of echocardiographic parameters between the two groups were analyzed ,and the ROC curve of each echocardiographic parameter for diagnosing LVEDP was draw n . Results T he parameters including flow propagation velocity ( VP) ,the ratio of filling fraction of E and A ( E/A) ,early diastolic filling deceleration time ( DT ) ,the duration of mitral A ( A‐dur ,) mitral annulus velocity at the septal side ( e′sep) ,systolic pulmonary venous flow velocity ( PVs) ,diastolic pulmonary venous flow velocity ( PVd ) and PVs/PVd were used to the diagnosis of the increasing of LVEDP ,however their accuracies were low ( AUC between 0 .5～0 .7) . T he parameters including left atrial volume index ( LAVI ) , tricuspid regurgitation ( T Rmax ) ,mitral annulus velocity in lateral wall of left ventricle ( e′lat ) ,average e′,E/e′sep ,E/e′lat ,average E/e′,velocity of pulmonary vein atrial reversal ( PVa) ,pulmonary vein atrial reversal duration ( Pva‐dur) ,the difference between the duration of pulmonary venous A wave and mitral A wave( PvaD‐AD) were also used to the diagnosis of the increasing of LVEDP , but their accuracies were still poor ( AUC between 0 .7～0 .9 ) . According to the real‐time left ventricular pressure measurement and different parameters of echocardiography ,the multivariate regression equation :LVEDP＝ 0 .292 LAVI + 0 .35 PVa + 0 .04 T Rmax + 0 .075 ( PvaD‐AD ) －0 .109 PVs －6 .773 was put forward as a correction standard ,the accuracy of the diagnosis of LVEDP was significantly improved ( AUC ＝0 .922) . Conclusions T he assessment of left ventricular diastolic function needs to be performed comprehensively with multiple parameters . T he multiple regression equation can accurately evaluate left ventricular diastolic function in patients with normal LVEF .

Exposure to bisphenol A during maternal pregnancy and the emotional and behavioral impact on their preschool children / 中华流行病学杂志

Objective: To explore the long-term effects of maternal pregnancy bisphenol A (BPA) exposure on emotional and behavioral problems appeared in their preschool children. Methods: The study sample was a subset of the China-Anhui Birth Cohort Study (C-ABCS). A unified questionnaire was used to collect basic information on both pregnant women and their children. Free BPA concentration in maternal serum was determined by high-performance liquid chromatographytandem mass spectrometry (HPLC-MS/MS). The parent-report version of the Strengths and Difficulties Questionnaire (SDQ) was used to estimate the emotional and behavioral problems in preschool children. A total of 1 713 pairs of mothers and children were included in this study. Association between BPA exposure during pregnancy and the emotional and behavioral problems in preschool children was evaluated with multinomial logistic regression model. Results: Prevalence rates in 1 713 preschool children appeared as: 6.48% of emotional problems, 8.11% for conduct problems, 8.35% for hyperactivity/inattention, 2.86% for peer problems, 11.38% for prosocial behaviors and 7.94% for total difficulties. Subjects were divided according to the degrees of exposure and the results showed as: low exposure group (≤0.120 ng/ml), medium exposure group (0.120<BPA<0.400 ng/ml) and high exposure group (≥0.400 ng/ml) according to the serum BPA concentration in tertile. Results from the multivariate logistic regression analysis showed that high level of maternal BPA exposure appeared a risk factor on children's abnormal conducts (OR=1.876, 95% CI: 1.161-3.029), more obvious in boys (OR=2.291, 95%CI: 1.126-4.661). Conclusion: Maternal exposure to high level of BPA during pregnancy might increase the detrimental effects of abnormal conducts in their preschool children, more obviously seen in boys.

Changes of proportion regarding consistent condom use and syphilis infection among low-fee female sex workers aged 35 and above / 中华流行病学杂志

Objective: To investigate the changes of proportion on both consistent condom use and syphilis infection among low-fee female sex workers aged 35 and above (LFSW), in order to provide evidence for targeted intervention strategies. Methods: A total of six cities-Liuzhou city and Pingnan couty of Guigang city of Guangxi Zhuang Autonomous Region, Jinghong city of Xishuangbanna Dai autonomous prefecture and Dali city of Dali Bai autonomous prefecture of Yunnan province, Zhangjiajie city and Jianghua Yao autonomous county of Yongzhou city Hunan province were involved in this study, with 60 eligible participants needed in each city, estimated through a pre-study. The first cross-sectional survey was completed from October 2012 to January 2013. Face-to-face questionnaire interview was carried out to collect information on socio-demography, work-related information and condom use situation. Blood was collected for syphilis testing. The second cross-sectional survey was carried out from June to September, 2015 under the same procedure. Results: A total of 371 and 403 eligible participants were included in the first and second survey, respectively. When comparing the two surveys, we noticed that the average age showed a slight change, from 42.4 years to 43.8 years old (t=3.537, P<0.001) and the average price for every commercial sex exchange increased from 36.8 RMB to 49.5 RMB (t=11.961, P<0.001). In the first survey, 46.9% (174/371) of the participants had more than two years of experience working as LFSW, compared to 61.3% (247/403) in the second survey (χ(2)=16.125, P<0.001). Also, 46.9% (174/371) of the participants consistently used condoms with clients in the past month in the first survey versus 64.3% (259/403) (χ(2)=23.641, P<0.001) in the second one. Rates of syphilis infection were found from 15.9% (59/371) in the first survey reduced to 7.2% (29/403) in the second survey (χ(2)=14.533, P<0.001). Conclusion: Compared with the first survey, the proportion of consistent condoms use showed an increase. Although the proportion of syphilis infection decreased in the second survey, the scope did not meet the criteria on syphilis, set by the government. Targeted intervention strategies on condom promotion and syphilis control should be implemented consistently in this population.

Age-related modification effect on the association between body mass index and the risk of hypertension: A Cohort Study on Chinese people living in the rural areas / 中华流行病学杂志

Objective: To study the modification effect of age on the association between body mass index and the risk of hypertension. Methods: People age ≥18 years old were selected by clusters, from a rural area of Henan province. In total, 20 194 people were recruited at baseline during 2007 and 2008, and the follow-up study was completed from 2013 to 2014. Logistic regression model was used to assess the risk of incident hypertension by baseline BMI and age-specific BMI. Results: During the 6-year follow-up period, 1 950 hypertensive persons were detected, including 784 men and 1 166 women, with cumulative incidence rates as 19.96%, 20.51%, and 19.61%, respectively. Compared with those whose BMI<22 kg/m(2), the RRs of hypertension were 1.09 (0.93-1.27), 1.17 (1.01-1.37), 1.34 (1.14-1.58) and 1.31 (1.09-1.56) for participants with BMI as 22-, 24-, 26- and ≥28 kg/m(2), respectively. In young and middle-aged populations, the risk of hypertension gradually increased with the rise of BMI (trend P<0.05). However, in the elderly, the increasing trend on the risk of hypertension risk was not as significantly obvious (trend P>0.05). Conclusion: The effect of BMI on the incidence of hypertension seemed to depend on age. Our findings suggested that a weight reduction program would be more effective on young or middle-aged populations, to prevent the development of hypertension.

Association between pregnancy-related anxiety of pregnant women and autism-like behavior in their offspring at 18 months of age / 中华流行病学杂志

Objective: To investigate the relationship of pregnancy-related anxiety of pregnant women in second/third trimesters and autism-like behaviors in their offspring at 18 months of age. Methods: Based on a prospective cohort study design, we evaluated the situation of pregnancy-related anxiety of women during second and third trimesters through a Pregnancy-Related Anxiety Questionnaire. Subjects under study were classified into three groups, 1) those with pregnancy- related anxiety during both trimesters, 2) those with pregnancy-related anxiety at one trimester and 3) those without pregnancy-related anxiety in either trimester. When their children were 18 months, autism-like behaviors (ALB) were evaluated, using the part A of Checklist for Autism in Toddlers-23, and then classified into three groups as non-ALB group, minor ALB group and major ALB group. Multi-nominal logistic Regression was used to analyze the relationship of pregnancy-related anxiety with autism-like behaviors. Results: Compared with non-ALB group, children whose mother with pregnancy-related anxiety during both trimesters presented significant higher risk on ALB than children whose mother without pregnancy-related anxiety in these two periods (relative risk, RR=2.43, 95% CI: 1.21-4.86, P=0.012), major factors as pregnant women's IQ and gestational diabetes mellitus, premature delivery and education levels of fosterers on these pregnant women were under control. Our results from the stratified analysis showed: when in the subgroup that mother was the main fosterer of the child, there was an significant increase of risk in children whose mothers with pregnancy-related anxiety during both trimesters (RR=4.22, 95%CI: 1.73-10.32, P=0.002). Conclusion: The association between pregnancy-related anxiety and autism-like behavior was not strong but influenced by the fosterer of the child.

A cohort study on body mass index and risk of all-cause mortality among hypertensive population / 中华流行病学杂志

Objective: To investigate the relationship between body mass index (BMI) and all-cause mortality in hypertensive population. Methods: All participants were selected from a prospective cohort study based on a rural population from Henan province, China. Cox proportional hazards regression models were used to estimate the associations of different levels of BMI stratification with all-cause mortality. Restricted cubic spline models were used to detect the dose-response relation. Results: Among the 5 461 hypertensive patients, a total of 31 048.38 person-years follow-up was conducted. The median of follow-up time was 6 years, and 589 deaths occurred during the follow-up period. Compared to normal weight group (18.5 kg/m(2)<BMI<24.0 kg/m(2)) the multivariate-adjusted hazard ratios for all-cause mortality associated with BMI levels (<18.5 kg/m(2), 24-28 kg/m(2), and ≥28 kg/m(2)) were 0.83 (95%CI: 0.37-1.87), 0.81 (95%CI: 0.67-0.97), and 0.72 (95%CI: 0.56-0.91), respectively. The dose-response analysis showed a nonlinear, reverse "S" shaped relationship (non-linearity P<0.001). Conclusion: Overweight or obese might have a protective effect on all-cause mortality in hypertensive population, which supports the "obesity paradox" phenomenon.

Spatial-temporal distribution characteristics of hepatitis E in Shanghai, 2006-2016 / 中华流行病学杂志

Objective: To understand the epidemiologic characteristics and spatial-temporal distribution of hepatitis E in Shanghai between 2006 and 2016. Methods: The reported incidence of hepatitis E and health facilities' information between 2006 and 2016 were collected from the China Information System for Disease Control and Prevention. The geographic information were from Shanghai Surveying and Mapping Institute. The map scale was 1∶750 000. Global and local autocorrelation, and spatial-temporal detection methods were applied to determine the spatial-temporal characteristics of hepatitis E. Software ArcGIS 10.1 was used to analyze global and local spatial auto correlation of hepatitis E spatial clusters. Software SaTScan 9.4.4 was used to conduct scan for exploring the areas of hepatitis E temporal spatial clusters. Results: A total of 6 048 cases of hepatitis E were reported in Shanghai during 2006-2016. The average incidence was 2.14/100 000. Spatial auto correlation analysis indicated that there was significant spatial positive correlations and spatial-temporal clustering of hepatitis E in Shanghai, and the "high-high cluster" was mainly located in the downtown of the city. Conclusion: Understanding the spatial-temporal clustering areas of hepatitis E cases in Shanghai from 2006 to 2016 is important to the reasonable allocation of public health resources and effective prevention and control of hepatitis E.

Diagnostic and epidemiological features of the first two HIV-2 indigenous infections in Hunan province / 中华流行病学杂志

Objective: To study the diagnostic and epidemiological features of the first two HIV-2 indigenous cases in Hunan province. Methods: Blood samples from two individuals with "HIV antibody indeterminate" and HIV-2 specific band showed by HIV-1/2 western blotting method, were repeatedly collected and detected under HIV 1+2 strip immunoassay and PCR, in Changsha city, Hunan province, through March to November, 2017. An epidemiological survey was carried out at the same time. Results: Our findings showed that the two cases were sex partners, without histories of sexual contact with foreigners and the source of infection was unknown. Results from the HIV 1+2 antibody confirmation test showed that they were "HIV-2 antibody positive" . Through amplifying and sequencing the gag area of HIV-2 and BLAST, the similarity of HIV-2 strains presented as 98%. The results also showed that there were HIV-2 specific fragments in the two cases. Conclusion: HIV-2 indigenous cases had never been reported in China. These cases had brought new challenge on prevention, diagnosis and treatment of HIV/AIDS in China.

Relations between pregestational body mass index, gestational weight gain and birth weight of neonates among women in the Southwest areas of China: A prospective cohort study / 中华流行病学杂志

Objective: To explore the effects of both pre-gestational BMI and gestational weight gain (GWG) on the birth weight of neonates. Methods: A total of 5 395 pregnant women were selected from the Southwest areas of China (Sichuan/Yunnan/Guizhou) and were divided into groups as pre-gestational underweight, normal weight, overweight and obesity, according to the WHO Recommendation on BMI Classification. Guidelines on Pregnancy weight were adopted from the Institute of Medicine to confirm the accuracy of GWG. Multinomial logistic regression model was used to assess the associations between pregestational BMI and GWG, on the birth weight of the neonates. Results: After adjusting for related confounders, low pre-gestational BMI appeared as a risk factor for SGA (OR=1.91, 95%CI: 1.47-2.50), and was also associated with the decreased risk of LGA (OR=0.55, 95%CI: 0.47-0.66). Inadequate GWG was both associated with the increased risk of delivering SGA (OR=1.57, 95%CI: 1.21-2.03) and the decreased risk of LGA (OR=0.48, 95%CI: 0.41-0.57). Pre-gestational overweight/obesity (OR=1.85, 95%CI: 1.58-2.17) and excessive GWG (OR=1.87, 95%CI: 1.67- 2.11) were both positively associated with the risks on LGA. Data from the stratified analysis indicated that inadequate GWG was positively associated with the risk of SGA among underweight or normal weight women (all P<0.05), but not with those overweight/obese women. Conclusions: Pre-gestational BMI and GWG were important influencing factors on the birth weight of neonates. Health education programs for pregnant women should be intensified and gestational weight gain should also be reasonably under control.

Breakthrough cancer medicine and its impact on novel drug development in China: report of the US Chinese Anti-Cancer Association (USCACA) and Chinese Society of Clinical Oncology (CSCO) Joint Session at the 17th CSCO Annual Meeting / 癌症

The US Chinese Anti-Cancer Association (USCACA) teamed up with Chinese Society of Clinical Oncology (CSCO) to host a joint session at the17th CSCO Annual Meeting on September 20th, 2014 in Xiamen, China. With a focus on breakthrough cancer medicines, the session featured innovative approaches to evaluate breakthrough agents and established a platform to interactively share successful experiences from case studies of 6 novel agents from both the United States and China. The goal of the session is to inspire scientific and practical considerations for clinical trial design and strategy to expedite cancer drug development in China. A panel discussion further provided in-depth advice on advancing both early and full development of novel cancer medicines in China.

Immune checkpoint inhibitors in clinical trials / 癌症

Immunology-based therapy is rapidly developing into an effective treatment option for a surprising range of cancers. We have learned over the last decade that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called "immune checkpoints." These checkpoints serve to control or turn off the immune response when it is no longer needed to prevent tissue injury and autoimmunity. Cancer cells have learned or evolved to use these mechanisms to evade immune control and elimination. The development of a new therapeutic class of drugs that inhibit these inhibitory pathways has recently emerged as a potent strategy in oncology. Three sets of agents have emerged in clinical trials exploiting this strategy. These agents are antibody-based therapies targeting cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). These inhibitors of immune inhibition have demonstrated extensive activity as single agents and in combinations. Clinical responses have been seen in melanoma, renal cell carcinoma, non-small cell lung cancer, and several other tumor types. Despite the autoimmune or inflammatory immune-mediated adverse effects which have been seen, the responses and overall survival benefits exhibited thus far warrant further clinical development.

IGF-1R as an anti-cancer target--trials and tribulations / 癌症

Type I insulin-like growth factor receptor (IGF-1R) has long been recognized for its role in tumorigenesis and growth, but only recently have the tools for targeting the IGF pathway become available. More than 10 IGF/IGF-1R inhibitors have entered clinical trials, and these belong to three main classes: (1) monoclonal antibodies against IGF-1R, (2) monoclonal antibodies against IGF-1R ligands (IGF-1 and IGF-2), and (3) IGF-1R tyrosine kinase inhibitors. These IGF-1R-targeting agents share common effects on IGF-1R signaling but differ in mechanisms of action, spectrum of target inhibition, and pharmacological features. Clinical activity of IGF-1R inhibitors has been demonstrated with sustained responses in a small number of patients with select tumor types, such as Ewing sarcoma and thymoma. However, many large clinical trials involving patients with adult tumors, including non-small cell lung cancer, breast cancer, and pancreatic cancer, failed to show clinical benefit in the overall patient population. Possible reasons for failure include the complexity of the IGF-1R/insulin receptor system and parallel growth and survival pathways, as well as a lack of patient selection markers. While IGF-1R remains a valid target for selected tumor types, identification of predictive markers and rational combinations will be critical to success in future development.

Phylogeny of diplozoids in five genera of the subfamily Diplozoinae Palombi, 1949 as inferred from ITS-2 rDNA sequences.

The phylogenetic relationship of 5 genera, i.e. Diplozoon Nordmann, 1832, Paradiplozoon Achmerov, 1974, Inustiatus Khotenovsky, 1978, Sindiplozoon Khotenovsky, 1981, and Eudiplozoon Khotenovsky, 1985 in the subfamily Diplozoinae Palombi, 1949 (Monogenea, Polyopisthocotylea) was inferred from rDNA ITS-2 region using neighbour-joining (NJ), maximum likelihood (ML) and Bayesian methods. The phylogenetic trees produced by using NJ, ML and Bayesian methods exhibit essentially the same topology. Surprisingly, freshwater species of Paradiplozoon from Europe clustered together with species of Diplozoon, but separated from Chinese Paradiplozoon species. The results of molecular phylogeny and lower level of divergence (4.1-15.7%) in ITS-2 rDNA among Paradiplozoon from Europe and Diplozoon and, on the other hand, high level of divergence (45.3-53.7%) among Paradiplozoon species from Europe and China might indicate the non-monophyletic origin of the genus Paradiplozoon. Also, the generic status of European Paradiplozoon needs to be revised. The species of Paradiplozoon in China is a basal group in Diplozoinae as revealed by NJ and Bayesian methods, and Sindiplozoon appears to be closely related to European Paradiplozoon and Diplozoon with their relationship to Eudiplozoon and Inustiatus being unresolved.