[Comparison of aspirin treatment strategies for primary prevention of cardiovascular diseases: A decision-analytic Markov modelling study].

OBJECTIVE: To compare the expected population impact of benefit and risk of aspirin treatment strategies for the primary prevention of cardiovascular diseases recommended by different guidelines in the Chinese Electronic Health Records Research in Yinzhou (CHERRY) study. METHODS: A decision-analytic Markov model was used to simulate and compare different strategies of aspirin treatment, including: Strategy ①: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk, recommended by the 2020 Chinese Guideline on the Primary Prevention of Cardiovascular Diseases; Strategy ②: Aspirin treatment for Chinese adults aged 40-59 years with a high 10-year cardiovascular risk, recommended by the 2022 United States Preventive Services Task Force Recommendation Statement on Aspirin Use to Prevent Cardiovascular Disease; Strategy ③: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk and blood pressure well-controlled (< 150/90 mmHg), recommended by the 2019 Guideline on the Assessment and Management of Cardio-vascular Risk in China. The high 10-year cardiovascular risk was defined as the 10-year predicted risk over 10% based on the 2019 World Health Organization non-laboratory model. The Markov model simulated different strategies for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Quality-adjusted life year (QALY) and the number needed to treat (NNT) for each ischemic event (including myocardial infarction and ischemic stroke) were calculated to assess the effectiveness of the different strategies. The number needed to harm (NNH) for each bleeding event (including hemorrhagic stroke and gastrointestinal bleeding) was calculated to assess the safety. The NNT for each net benefit (i.e., the difference of the number of ischemic events could be prevented and the number of bleeding events would be added) was also calculated. One-way sensitivity analysis on the uncertainty of the incidence rate of cardiovascular diseases and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. RESULTS: A total of 212 153 Chinese adults, were included in this study. The number of people who were recommended for aspirin treatment Strategies ①-③ was 34 235, 2 813, and 25 111, respectively. The Strategy ③ could gain the most QALY of 403 [95% uncertainty interval (UI): 222-511] years. Compared with Strategy ①, Strategy ③ had similar efficiency but better safety, with the extra NNT of 4 (95%UI: 3-4) and NNH of 39 (95%UI: 19-132). The NNT per net benefit was 131 (95%UI: 102-239) for Strategy ①, 256 (95%UI: 181-737) for Strategy ②, and 132 (95%UI: 104-232) for Strategy ③, making Strategy ③ the most favorable option with a better QALY and safety, along with similar efficiency in terms of net benefit. The results were consistent in the sensitivity analyses. CONCLUSION: The aspirin treatment strategies recommended by the updated guidelines on the primary prevention of cardiovascular diseases showed a net benefit for high-risk Chinese adults from developed areas. However, to balance effectiveness and safety, aspirin is suggested to be used for primary prevention of cardiovascular diseases with consideration for blood pressure control, resulting in better intervention efficiency.

[Epidemiological study on the incidence of inflammatory bowel disease in Yinzhou District, Ningbo City from 2011 to 2020].

OBJECTIVE: To describe the distribution characteristics of inflammatory bowel disease among permanent residents in Yinzhou District, Ningbo City, and to understand the disease burden and development trend of inflammatory bowel disease in this area. METHODS: Using the retrospective cohort design, we collected the registration information of all permanent residents in the residents' health files of the Yinzhou Regional Health Information Platform from 2010 to 2020, and used electronic medical records to follow up their inflammatory bowel disease visits. A one-year wash-out period was set, and the patients who were diagnosed with the primary diagnosis for the first time after one year of registration were re-garded as new cases. The incidence density and 95% confidence interval (CI) of inflammatory bowel disease were estimated by Poisson distribution. RESULTS: From 2011 to 2020, a total of 1 496 427 permanent residents in Yinzhou District were included, of which 729 996 were male (48.78%). The total follow-up person-years were 8 081 030.82, and the median follow-up person-years were 5.41 [interquartile range (IQR): 5.29]. During the study period, there were 1 217 new cases of inflammatory bowel disease, of which males (624 cases, 51.27%) were more than females (593 cases, 48.73%). The total incidence density was 15.06/100 000 person-years (95%CI: 14.23, 15.93). Among all new cases, there were 1 106 cases (90.88%) of ulcerative colitis, with an incidence density of 13.69 per 100 000 person-years (95%CI: 12.89, 14.52); 70 cases (5.75%) of Crohn's disease, with an incidence density of 0.87 per 100 000 person-years (95%CI: 0.68, 1.09); and 41 cases (3.37%) of indeterminate colitis, with an incidence density of 0.51 per 100 000 person-years (95%CI: 0.36, 0.69). The median age of onset of ulcerative colitis was 50.82 years old (IQR: 18.77), with the highest proportion (15.01%) in the 45-49 years group. The incidence density of ulcerative colitis gradually increased with age, reaching a relatively high level in the 45-49 years group (20.53/100 000 person-years; 95%CI: 17.63, 23.78), followed by a slight increase. And the incidence density in the 65-69 years group was the highest (25.44/100 000 person-years; 95%CI: 20.85, 30.75), with a rapid decrease in the 75-79 years group. The median age of onset of Crohn's disease was 44.34 years (IQR: 33.41), with the highest proportion (12.86%) in the 25-29 years group. Due to the small number of new cases of Crohn's disease, the age distribution fluctuated greatly, with peaks both in young and old people. From 2011 to 2020, the incidence density of inflammatory bowel disease in Yinzhou District was at a low level from 2011 to 2013, and showed a rapid upward trend from 2014 to 2016, reaching a peak of 24.62 per 100 000 person-years in 2016 (95%CI: 21.31, 28.30), and slightly decreased in 2017-2020. CONCLUSION: The incidence density of inflammatory bowel disease in Yinzhou District from 2011 to 2020 was at a relatively high level, and medical institutions and health departments need to pay attention to the burden of disease caused by it.

[Effectiveness of statin treatment strategies for primary prevention of cardiovascular diseases in a community-based Chinese population: A decision-analytic Markov model].

OBJECTIVE: To evaluate the effectiveness of statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases by the Western guidelines in a community-based Chinese population from economically developed areas using data from the Chinese electronic health records research in Yinzhou (CHERRY) study. METHODS: A Markov model was used to evaluate the effectiveness of the following statin treatment strategies, including: (1) usual care without cardiovascular risk assessment(Strategy 0); (2) using the World Health Organization (WHO) non-laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 1); (3) using the WHO laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 2); and (4) using the Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR) model with statin treatment for high-risk group (risk ≥ 10%, Strategy 3). According to the guidelines, adults in the medium-risk group received lifestyle intervention, and adults in the high-risk group received life-style intervention and statin treatment under these strategies. The Markov model simulated different strategies for ten years (cycles) using parameters from the CHERRY study, published data, meta-analyses and systematic reviews for Chinese. The number of cardiovascular events or deaths, as well as the number need to treat (NNT) with statin per cardiovascular event or death prevented, were calculated to compare the effectiveness of different strategies. One-way sensitivity analysis on the uncertainty of incidence rate of cardiovascular diseases, and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. RESULTS: Totally 225 811 Chinese adults aged 40-79 years without cardiovascular diseases at baseline were enrolled. In contrast to the usual care without risk assessment-based statin treatment strategy, Strategy 1 using the WHO non-laboratory-based risk charts could prevent 3 482 [95% uncertainty interval (UI): 2 110-4 661] cardiovascular events, Strategy 2 using the WHO laboratory-based risk charts could prevent 3 685 (95%UI: 2 255-4 912) events, and Strategy 3 using the China-PAR model could prevent 3 895 (95%UI: 2 396-5 181) events. NNTs with statin per cardiovascular event prevented were 22 (95%UI: 14-54), 21 (95%UI: 14-52), and 27 (95%UI: 17-67), respectively. Strategy 3 could prevent more cardiovascular events, while Strategies 1 and 2 required fewer numbers need to treat with statin per cardiovascular event prevented. The results were consistent in the sensitivity analyses. CONCLUSION: The statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases recommended by the Western guidelines could achieve substantive health benefits in adults from developed areas of China. Using the China-PAR model for cardiovascular risk assessment could prevent more cardiovascular diseases while using the WHO risk charts seems more efficient.

[Effectiveness of different screening strategies for type 2 diabete on preventing cardiovascular diseases in a community-based Chinese population using a decision-analytic Markov model].

OBJECTIVE: To evaluate the effectiveness of different screening strategies for type 2 diabetes to prevent cardiovascular disease in a community-based Chinese population from economically developed areas based on the Chinese electronic health records research in Yinzhou (CHERRY) study. METHODS: A Markov model was used to simulate different systematic diabetes screening strategies, including: (1) screening among Chinese adults aged 40-70 years recommended by the 2020 Chinese Guideline for the prevention and Treatment of Type 2 Diabetes (Strategy 1); (2) screening among Chinese adults aged 35 to 70 years recommended by the 2022 American Diabetes Association Standard of Medical Care in Diabetes (Strategy 2); and (3) screening among Chinese adults aged 35-70 years with overweight or obesity recommended by the 2021 United States Preventive Services Task Force Recommendation Statement on Screening for Prediabetes and Type 2 Diabetes (Strategy 3). According to the guidelines, individuals who were screened positively (fasting plasma glucose ≥ 7.0 mmol/L) would be introduced to intensive glycemic targets management (glycated hemoglobin < 7.0%).The Markov model simulated different screening scenarios for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Number of cardiovascular disease events or deaths could be prevented and number needed to screen (NNS) were calculated to compare the effectiveness of the different strategies. One-way sensitivity analysis on the sensitivity of screening methods and probabilistic sensitivity analysis on uncertainties of diabetes incidence, the sensitivity of screening methods, and intensive glycemic management effects were conducted. RESULTS: Totally 289 245 Chinese adults aged 35-70 years without cardiovascular diseases or diagnosed diabetes at baseline were enrolled. In terms of the number of cardiovascular disease events could be prevented, Strategy 1 for systematic diabetes screening among the adults aged 35-70 years was 222 (95%UI: 180-264), Strategy 2 for systematic diabetes screening among the adults aged 40-70 years was 227 (95%UI: 185-271), and Strategy 3 for systematic diabetes screening among the adults aged 35-70 years with obesity or overweight (body mass index ≥ 24 kg/m2) was 131 (95%UI: 98-164), compared with opportunistic screening. NNS per cardiovascular disease event for the strategies 1, 2 and 3 were 1 184 (95%UI: 994-1 456), 1 274 (95%UI: 1 067-1 564) and 814 (95%UI: 649-1 091), respectively. Compared with Strategy 1, NNS per cardiovascular disease event for Strategy 2 increased by 90 (95%UI: -197-381) with similar effectiveness of cardiovascular prevention; however, NNS per cardiovascular disease event for Strategy 3 was reduced by 460 (95%UI: 185-724) in contrast to the Strategy 2, suggesting that the Strategy 3 was more efficient. The results were consistent in multiple sensitivity analyses. CONCLUSION: Systematic screening for diabetes based on the latest guidelines in economically developed areas of China can reduce cardiovascular events and deaths. However, merely lowering the starting age of screening from 40 to 35 years seems ineffective for preventing cardiovascular disease, while screening strategy for Chinese adults aged 35-70 years with overweight or obesity is recommended to improve efficiency.

Comparing nanoparticle polymeric micellar paclitaxel and solvent-based paclitaxel as first-line treatment of advanced non-small-cell lung cancer: an open-label, randomized, multicenter, phase III trial.

BACKGROUND: Polymeric micellar paclitaxel (pm-Pac) is a novel Cremophor EL-free, nanoparticle micellar formulation of paclitaxel. We aimed to compare the efficacy and safety between pm-Pac plus cisplatin and solvent-based paclitaxel (sb-Pac) plus cisplatin in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 448 stage IIIB to IV NSCLC patients were randomly assigned (2:1) to receive six 3-week cycles of either pm-Pac (230 mg/m2) plus cisplatin (70 mg/m2; n = 300), followed by dose escalation of pm-Pac to 300 mg/m2 from the second 3-week cycle if prespecified toxic effects were not observed after the first cycle, or sb-Pac (175 mg/m2) plus cisplatin (70 mg/m2; n = 148). The primary end point was objective response rate (ORR) assessed by independent review committees (IRCs). The secondary end points included IRC-assessed progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Patients in the pm-Pac-plus-cisplatin group showed significant improvements in IRC-assessed ORR compared with those in the sb-Pac-plus-cisplatin group (50% versus 26%; rate ratio 1.91; P < 0.0001). Additionally, subgroup analysis showed that a higher ORR was consistently observed in both squamous and nonsquamous histological types. IRC-assessed median PFS was significantly higher in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group (6.4-month versus 5.3-month; hazard ratio 0.63; P = 0.0001). Median OS was not significantly different between the two groups. The incidence of treatment-related serious adverse events (9% versus 18%; P = 0.0090) was significantly lower in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group. CONCLUSION: Pm-Pac plus cisplatin yielded superior ORR and PFS along with a favorable safety profile and should become an option for patients with advanced NSCLC. CLINICAL TRIAL IDENTIFIER: ClinicalTrials.gov NCT02667743; https://clinicaltrials.gov/ct2/show/NCT02667743.

The association of metabolic health obesity with incidence of carotid artery plaque in Chinese adults.

BACKGROUND AND AIMS: We aimed to evaluate the association between different obese phenotypes with carotid artery plaque (CAP) event. METHOD AND RESULTS: The current retrospective cohort study was performed in 32,778 Chinese adults (19,221 men and 13,557 women, aged 41.9 ± 11.0 years). Obese phenotypes were assessed based on baseline body mass index (<24.0 vs. ≥24.0 kg/m2) and metabolic characteristics (health vs. unhealth). All the participants were further classified into four groups: metabolic health and normal weight (MHNW), metabolic unhealth and normal weight (MUHNW), metabolic health and overweight (MHO), and metabolic unhealth and overweight (MUHO). Ultrasound B-mode imaging was annually performed to evaluate CAP throughout the study. We have identified 2142 CAP cases during 5-year follow-up. Comparing with the MHNW group, the hazard ratios for the risk of incident CAP was 2.44 (95% CI:1.92 and 3.09) for the MUHNW group, 1.52 (95% CI:1.06 and 2.18) for the MHO group, and 1.8 (95% CI:1.4 and 2.33) for the MUHO group. The association was more pronounced in young adults (<65 y) than that in aged adults (≥65 y). Sensitivity analysis generated similar results with the main analysis. CONCLUSION: MUHNW, MHO, and MUHO were associated with the risk of CAP.

[Effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population: A decision-analytic Markov model].

OBJECTIVE: To evaluate the potential effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population from economically developed area of China. METHODS: Totally 202 179 adults aged 40 to 74 years without cardiovascular diseases at baseline (January 1, 2010) were enrolled from the Chinese electronic health records research in Yinzhou (CHERRY) study. Three scenarios were considered: the screening strategy based on risk charts recommended by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases in Chinese adults aged 40-74 years (Strategy 1); the screening strategy based on the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) models recommended by the 2019 Guideline on the assessment and management of cardiovascular risk in China in Chinese adults aged 40-74 years (Strategy 2); and the screening strategy based on the China-PAR models in Chinese adults aged 50-74 years (Strategy 3). According to the guidelines, individuals who were classified into medium- or high-risk groups after cardiovascular risk assessment by the corresponding strategies would be introduced to lifestyle intervention, while high-risk population would take medication in addition. Markov model was used to simulate different screening scenarios for 10 years (cycles), using parameters mainly from the CHERRY study, as well as published data, Meta-analyses and systematic reviews for Chinese populations. The life year gained, quality-adjusted life year (QALY) gained, number of cardiovascular disease events/deaths could be prevented and number needed to be screened (NNS) were calculated to compare the effectiveness between the different strategies. One-way sensitivity analysis on uncertainty of cardiovascular disease incidence rate and probabilistic sensitivity analysis on uncertainty of distributions for the hazard ratios were conducted. RESULTS: Compared with non-screening strategy, QALYs gained were 1 433 [95% uncertainty interval (UI): 969-1 831], 1 401 (95%UI: 936-1 807), and 716 (95%UI: 265-1 111) for the Strategies 1, 2, and 3; and the NNS per QALY in the above strategies were 141 (95%UI: 110-209), 144 (95%UI: 112-216), and 198 (95%UI: 127-529), respectively. The Strategies 1 and 2 based on different guidelines showed similar effectiveness, while more benefits were found for screening using China-PAR models in adults aged 40-74 years than those aged 50-74 years. The results were consistent in the sensitivity analyses. CONCLUSION: Screening for cardiovascular diseases in Chinese adults aged above 40 years seems effective in coastal developed areas of China, and the different screening strategies based on risk charts by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases or China-PAR models by the 2019 Guideline on the assessment and management of cardiovascular risk in China may have similar effectiveness.

[Association of high-density lipoprotein cholesterol with risk of cardiovascular disease mortality].

Objective: To analyze the association between high density lipoprotein cholesterol (HDL-C) and the risk of cardiovascular disease mortality. Methods: A total of 71 618 residents aged over 18 years with complete baseline data, who were filed on the health information big data platform of Yinzhou district, Ningbo city, Zhejiang Province from 2009 to 2014, were selected as the research population. The research population were divided into four groups according to the level of HDL-C: low-level group (HDL-C<1.0 mmol/L), intermediate-level group (1.0 mmol/L≤HDL-C<1.5 mmol/L), medium-high-level group (1.5 mmol/L≤HDL-C<2.0 mmol/L) and high-level group (HDL-C≥2.0 mmol/L). Cox proportional hazard model was used to calculate the risk ratio of cardiovascular diseases mortality in different groups. Results: The study population was followed up for a total of 427 989.4 person-years, follow-up time of (5.98±1.04)years. During the follow-up period, there were 799 deaths due to cardiovascular diseases. After adjusting for confounding factors, compared with the medium-high-level group as the reference group, the HR (95%CI) for cardiovascular diseases mortality was 1.43 (1.13-1.82) in the low-level group and 1.22 (1.02-1.46) in the high-level group. Conclusion: The low level of HDL-C (<1.5 mmol/L) is associated with a higher risk of cardiovascular disease deaths. The level of HDL-C can be used as a biological indicator to monitor the development of cardiovascular diseases and guide treatment.

Raman Study of Cooper Pairing Instabilities in (Li_{1-x}Fe_{x})OHFeSe.

We studied the electronic Raman spectra of (Li_{1-x}Fe_{x})OHFeSe as a function of light polarization and temperature. In the B_{1g} spectra alone we observe the redistribution of spectral weight expected for a superconductor and two well-resolved peaks below T_{c}. The nearly resolution-limited peak at 110 cm^{-1} (13.6 meV) is identified as a collective mode. The peak at 190 cm^{-1} (23.6 meV) is presumably another collective mode since the line is symmetric and its energy is significantly below the gap energy observed by single-particle spectroscopies. Given the experimental band structure of (Li_{1-x}Fe_{x})OHFeSe, the most plausible explanations include conventional spin-fluctuation pairing between the electron bands and the incipient hole band and pairing between the hybridized electron bands. The absence of gap features in A_{1g} and B_{2g} symmetry favors the second case. Thus, in spite of various differences between the pnictides and chalcogenides, this Letter demonstrates the proximity of pairing states and the importance of band structure effects in the Fe-based compounds.

[Differences in the bone marrow histopathology between pediatric acquired aplastic anemia and refractory cytopenia of childhood].

Objective: To study the differences in the bone marrow histopathology between acquired aplastic anemia (AAA) in children and refractory cytopenia of childhood (RCC) to facilitate their diagnoses and differential diagnosis. Methods: The clinical data and bone marrow biopsies of the RCC and AAA cases diagnosed from January 2008 to December 2018 in Xinhua Hospital, Shanghai Jiaotong University School of Medicine and Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University School of Medicine were analyzed. Results: A total of 71 AAA and 79 RCC cases were analyzed. There were 52 males and 19 females, age ranged 1.0-15.0 years (median, 8.9 years) in the AAA group, and 53 males and 26 females, age ranged 0.5-16.0 years (median, 5.0 years) in the RCC group. All the biopsy specimens of AAA patients had severe hypocellularity; the cellularity of 88.7% (63/71) specimens was under 5.0%, and 11.3%(8/71) was 5%-24%. None of the AAA specimens showed any dysplastic change. All the biopsy specimens of RCC patients had hypocellularity, including 94.9%(75/79) of the specimens with a cellularity of 5%-50%. All of the RCC specimens showed a patchy distribution of hematopoiesis. A dysplastic change of erythroid cells and micromegakaryocytes was found in 40.5% (32/79) and in 60.8% (48/79) of the RCC cases, respectively. Conclusions: The degree of hypocellularity, the distribution pattern of hematopoiesis, the cell composition and localization of erythroid cell clusters and the appearance of micromegaryocytes could help the diagnosis and differential diagnosis of AAA and RCC.

[Application of the pathological classification of "CCCG-WT-2016" (2019 revision) for treatment of Wilms tumors].

Objective: To describe our experiences in application of the 2019 revision of "CCCG-WT-2016" for the diagnosis of Wilms tumors. Methods: Ninety-one cases of Wilms tumor diagnosed at Shanghai Children's Medical Center from January 2015 to December 2018 were collected. All cases were reviewed by two senior pathologists, including one from China and the other from Singapore, according to the 2019 revision of "CCCG-WT-2016." Results: The specimens were obtained by core biopsy (n=21), primary nephrectomy (n=41), post-chemotherapy nephrectomy/resection (n=18), or biopsy/resection of metastatic/relapse/post-chemotherapy metastatic lesion(s) (n=11). The specimens of core biopsy and primary nephrectomy (n=62) all had favorable histology.Twelve post-chemotherapy nephrectomy cases were subdivided into three risk groups: low risk (n=0), intermediate risk (n=10) and high risk (n=2). Six post-chemotherapy resection cases were subdivided into 3 risk groups:low risk (n=0), intermediate risk (n=5) and high risk (n=1). The remaining 11 cases were comprised of metastatic, relapse, and post-chemotherapy metastatic lesions. The concordance rate of the two senior pathologists was 100%(91/91). Conclusions: The 2019 revision of "CCCG-WT-2016" is clearly written and easy to use. It can serve as the basis of accurate classification for clinical treatment.

[Clinicopathological characteristics of NTRK-rearranged mesenchymal tumors in childhood].

Objective: To investigate the clinical and pathological features of pediatric NTRK-rearranged tumors. Methods: Four NTRK-rearranged soft tissue tumors and one renal tumor at Shanghai Children's Medical Center, Shanghai Jiaotong University and Singapore KK Women's and Children's Hospital from January 2017 to September 2019 were identified. Pan-TRK immunohistochemistry, and the ALK and ETV6 gene break-apart fluorescence in situ hybridizations (FISH) were performed. NTRK gene rearrangement was detected using sequencing-based methods. Results: There were 3 males and 2 females in this study. The patients were between 3 months and 13 years of age. Histologically, the tumors were infiltrative spindle cell tumors with variable accompanying inflammatory cells. Immunohistochemistry showed positive reactivity for pan-TRK in all tumors, with nuclear staining for NTRK3 fusion, and cytoplasmic staining for NTRK1 fusion. The molecular testing revealed NTRK gene fusions (one each of TPM3-NTRK1, ETV6-NTRK3 and DCTN1-NTRK1, and two cases of LMNA-NTRK1). Two patients were receiving larotrectinib. The others were are well without disease, with follow-up durations of 9 to 29 months. Conclusions: NTRK-rearranged mesenchymal tumors from soft tissue sites and kidney are identified. A novel DCTN1-NTRK1 fusion is described. Pan-TRK immunohistochemistry is useful for diagnosis. NTRK-targeted therapy may be an option for unresectable, recurrent or metastatic cases.

[Effect of sorafenib and prophylactic TACE for prevention of postoperative relapse in patients with liver cancer combined with microvascular invasion].

Objective: To study the effect of sorafenib and prophylactic transarterial chemoembolization (TACE) for prevention of postoperative relapse in patients with liver cancer combined with microvascular invasion (MVI) after using radical hepatectomy. Methods: A retrospective analysis was performed on 137 cases that underwent radical hepatectomy at the First Affiliated Hospital of Zhengzhou University from August 2015 to January 2018. Clinical data of liver cancer patients with MVI were diagnosed by postoperative pathology. General data of the three groups were analyzed. Kaplan-Meier was used to calculate the tumor-free survival rate. COX proportional hazards-model was used to analyze the independent risk factors for postoperative recurrence of liver cancer with MVI recurrence. Counting data was compared by x(2) test between groups, and log-rank test was used to compare the tumor-free survival rates. Results: A, B, and C groups had 49, 36, and 52 cases, respectively. General clinicopathological data of the three groups were not statistically significant. The postoperative tumor-free survival rates at 1-, 2-, and 3-years were 71.4%, 51.0%, 38.8%, 86.1%, 75.0%, 66.7%, and 82.7%, 75.0%, and 59.6% respectively in A, B, and C groups. Multivariate Cox proportional-hazards regression model showed that patients' age (HR = 0.622, P = 0.046), maximum tumor diameter (HR = 1.661, P = 0.033), prophylactic TACE (HR = 0.544, P = 0.019), and postoperative use of sorafenib (HR = 0.419, 0.222, 0.791, P = 0.007) were independent risk factors for postoperative recurrence of liver cancer with MVI. Conclusion: Sorafenib or prophylactic TACE use can significantly reduce the recurrence rate within 3 years after radical surgery in patients with liver cancer who were confirmed to have MVI by postoperative pathology.

Association of genetic ancestry with striatal dopamine D2/D3 receptor availability.

Despite ethnic differences in allele frequencies of variants in dopaminergic genes associated with dopamine D2/D3 receptor availability (D2R), no study to date has investigated the relationship between genetic ancestry and striatal D2R. Here, we show that ancestry-informative markers significantly predict dorsal striatal D2R in 117 healthy ethnically diverse residents of the New York metropolitan area using Positron Emission Tomography (PET) with [11C]raclopride (P<0.0001), while correcting for age, sex, BMI, education, smoking status, and estimated socioeconomic status (ZIP codes). Effects of ethnicity on D2R were not driven by variation in dopaminergic candidate genes. Instead, candidate gene associations with striatal D2R were diminished when correcting for ancestry. These findings imply that future studies investigating D2 receptor genes should covary for genetic ancestry or study homogeneous populations. Moreover, ancestry studies on human neurobiology should control for socioeconomic differences between ethnic groups.

[Incidence and risk factors of chronic kidney disease in community-based patients with diabetes].

OBJECTIVE: To estimate the incidence rate and effects of risk factors on chronic kidney disease (CKD) in Chinese patients with diabetes, based on Electronic Health Records (EHRs) from the Chinese Electronic health Records Research in Yinzhou (CHERRY) Study. METHODS: Using the CHERRY cohort study with the individual-level information on chronic disease management; and health administrative, clinical and laboratory databases, patients with diabetes without kidney disease at baseline were enrolled and followed up from January 2009 through December 2016. CKD was defined as the estimated glomerular filtration rate(eGFR) <60 mL/(min×1.73 m2) or urine albumin/creatinine ratio (ACR)≥3 mg/mmol. Standardized incidence rates of CKD in diabetic population were calculated according to the 2010 China census data. Cox proportional hazards models were used to explore the association of risk factors on CKD in patients with diabetes. RESULTS: Over a median 3.2 years of follow-up, 13 829 patients with diabetes were included in this analysis and 1 087 developed CKD. The crude and standardized incidence rate was 23.7(95%CI: 22.3-25.2) and 14.8(95%CI:12.1-17.6) per 1 000 person-years respectively. The incidence rate for developing CKD in patients with diabetes aged over 60 years was higher than those aged 60 and below (26.6 vs. 11.5 per 1 000 person-years, P<0.05). Cox proportional hazards models showed that age over 60 years(HR=1.88, 95%CI: 1.51-2.35), hypertension (HR=1.81, 95%CI: 1.56-2.10), total cholesterol (HR=1.07, 95%CI: 1.00-1.14) and duration of diabetes (HR per year increment=1.02, 95%CI: 1.00-1.03) and the level of high density lipoprotein cholesterol (HDLC, HR=0.49, 95%CI: 0.40-0.61) were significantly associated with CKD. No statistical significance was found for sex, smoking status, alcohol use and average level of fasting glucose (All P>0.05). Subgroup analysis indicated that even when the lipid levels were well-controlled, comorbidity of hypertension was still associated with CKD in the patients with diabetes. CONCLUSION: Incidence rate of chronic kidney disease in this Chinese population with diabetes was high. Age and comorbidity of hypertension were the most important risk factors for CKD, suggesting the priority for CKD screening in patients with diabetes in China. Control of blood pressure and lipid were especially crucial to prevent CKD in patients with diabetes.

[Effect of simplified and traditional Chinese character on accommodative microfluctuation in young adult myopes and emmetropes].

Objective: This study investigates the effect of simplified and traditional Chinese character on accommodative microfluctuation in young adult myopes and emmetropes. Methods: Prospective cohort study. Based on refractive errors, Young adult candidates (18-28 years) were classified into two groups based on their spherical equivalent degrees: emmetropes (n=18), myopes (n=18). Four different reading targets (12pt size simplified and traditional Chinese characters, and 8pt size simplified and traditional Chinese characters) were displayed on computer screen collectively for 135s. The accommodative microfluctuation of the candidates were measured using the free space Grand-Seiko WAM-5500 autorefractor. Results: The results indicated that the type of character (simplified and traditional) had significant influence on accommodative microfluctuation. For myopic candidates, the accommodative microfluctuation for traditional Chinese character was greater than that for simplified Chinese character [traditional Chinese character: (0.35±0.17) D, vs. simplified Chinese character: (0.29±0.11) D, t=2.556, P=0.017], however as for emmetropic candidates, the difference between the accommodative microflucuation for the two types of characters was of no statistical significance [traditional Chinese character: (0.24±0.11) D, vs. simplified Chinese character: (0.24±0.12) D, t=0.004, P=0.996]. There was a difference between emmetropic and myopic candidates in terms of accommodative microfluctuation for traditional Chinese character, myopes had greater accommodative microfluctuation than emmetropes (t=3.140, P=0.02). However the difference between emmetropic and myopic candidates in terms of accommodative microfluctuation for simplified Chinese character was of no statistical significance (t=1.866, P=0.066). Conclusions: The results of the study indicated that myopes were more susceptible than emmetropic in accommodative microfluctuation when reading traditional Chinese character of high spatial frequency. (Chin J Ophthalmol, 2018, 54: 288-293).

[Study on the difference of binocular accommodative response between atients with intermittent exotropia under different viewing condition].

Objective: To evaluate the accommodative response of patients with intermittent exotropia (IXT) objectively, and study the changes of accommodative response of intermittent exotropia patients when maintaining binocular fusion. Methods: The prospective cohort study was used in this study. Twenty-four patients diagnosed with basic intermittent exotropia who visited the eye hospital of Wenzhou Medical University during October 2016 through January 2017 together with 24 normal volunteers were included, the 48 participants aged from 10 to 27 years old. The participants were divided into the case group and the control group. There were 11 males and 13 females in the case group, and 7 males and 17 females in the control group. The Open-filed autorefractor WAM-5500 (Grand Seiko, Japan) was used to measure the accommodative response of each eye under binocular and monocular viewing conditions at 5 m and 40 cm respectively. During the measurement, patients wore full correction spectacles to achieve distant best-corrected visual acuity of both eyes. The accommodative responses of each eye under binocular and monocular viewing conditions at distance or near between fellow eyes and groups were compared. Results: Under near fixation (40cm) binocular viewing conditions, the accommodative response of the fixating eye (-1.915±0.301)D was different from the deviating eye -1.649(-2.020, -0.304)D in the case group (Z=-3.714, P<0.001). Under near fixation monocular viewing conditions, the accommodative response of the fixating eye (-1.653±0.271)D was also different from the deviating eye -1.565 (-2.031, -0.667)D in the case group (Z=-2.971, P=0.003). During binocular viewing, the asymmetric value of the accommodative response between both eyes of the case group was 0.389(0.102, 1.458)D which was more significant than the normal controls' 0.155(0.009, 0.573)D (Z=-3.505, P<0.001), but during monocular viewing, there was no significant difference between the groups (Z=-1.908, P=0.056). Under near viewing conditions, the variation value of the fixating eyes of the case group was -0.228(-0.796, 0.382)D, which was greater than the variation value -0.086(-0.606, 0.628)D of the right eye of the normal controls, such difference is of statistical significance (Z=-2.279, P=0.023). Under distance viewing conditions, there was no significant difference in the accommodative response between fixating eyes and deviating eyes in case group neither during monocular viewing nor binocular viewing (t=-1.525, -1.729, P>0.05). Besides, the asymmetric values of accommodative response between groups were not significantly different (Z=-1.433, P=0.152. Z=-0.938, P=0.348). Under distance viewing conditions, the changes in accommodative response of each eye during both monocular viewing and binocular viewing were not significantly different between case group and normal controls (Z=-0.041, P=0.967. Z=-1.433, P=0.152). Conclusions: The accommodative responses of the fixating eye and deviating eye of patients with intermittent exotropia were asymmetric under near fixation binocular viewing conditions, and the accommodative response of the deviating eye tends to decrease. Besides, the change of accommodative response of the patients with intermittent exotropia when maintaining binocular fusion is more significant than that of the normal controls. (Chin J Ophthalmol, 2018, 54: 55-61).

MicroRNA-1285 inhibits malignant biological behaviors of human pancreatic cancer cells by negative regulation of YAP1.

Pancreatic ductal adenocarcinoma is a most deadly malignancy, with a 5-year survival rate of ~7%. Chemotherapy is the main treatment strategy of this disease. However, the high rate of resistance to chemotherapeutic agent contributes to poor prognosis. MicroRNAs are essential for the initiation, progression and chemoresistance of human malignancies. Previous studies have shown that miRNA-1285 participates in renal cell carcinoma and hepatocellular carcinoma. However, its roles in pancreatic ductal adenocarcinoma are poorly understood. In this study, we confirmed that miR-1285 was significantly down-regulated in gemcitabine-resistant pancreatic cancer cell lines by qRT-PCR. We found that miR-1285 suppressed cell proliferation as well as increased the sensitivity of PDAC cells to gemcitabine by CCK8 assays in vitro. Results from transwell assay indicated that miR-1285 inhibited pancreatic cancer cell migration and invasion. Experiments using different cell lines got identical results. All those results demonstrated that miR-1285 act as tumor suppressor of pancreatic cancer. To our knowledge, this study is the first to elucidate the function of miR-1285 in pancreatic cancer. Western blotting analysis verified that miR-1285 negatively regulated YAP1 protein level, together with EGFR and ß-catenin. YAP1 is a known oncoprotein of pancreatic cancer. As silencing of YAP1 activity might be beneficial in cancer prevention and treatment, our results suggest that miR-1285 might serve as a novel therapeutic target for miRNA-based therapy in pancreatic cancer. Further research elucidating the exact mechanisms of miRNA-1285 function and the correlation between miR-1285 levels in tissues or serum and clinical characteristics of pancreatic cancer is needed later.

Towards water sensitive cities in Asia: an interdisciplinary journey.

Rapid urbanisation, population growth and the effects of climate change drive the need for sustainable urban water management (SUWM) in Asian cities. The complexity of this challenge calls for the integration of knowledge from different disciplines and collaborative approaches. This paper identifies key issues and sets the stage for interdisciplinary research on SUWM in Asia. It reports on the initial stages of a SUWM research programme being undertaken at Monash University, Australia, and proposes a framework to guide the process of interdisciplinary research in urban water management. Three key themes are identified: (1) Technology and Innovation, (2) Urban Planning and Design, and (3) Governance and Society. Within these themes 12 research projects are being undertaken across Indonesia, China, India and Bangladesh. This outward-looking, interdisciplinary approach guides our research in an effort to transgress single-discipline solutions and contribute on-ground impact to SUWM practices in Asia.