Efficacy and safety of dupilumab plus topical tacrolimus for atopic dermatitis in 6- to 12-year-old patients.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of combining dupilumab with topical tacrolimus for the treatment of atopic dermatitis (AD) in children aged 6 to 12 years. PATIENTS AND METHODS: A total of 168 pediatric (aged 6 to 12 years) patients with severe AD admitted to our hospital between April 2022 and April 2023 were included in this retrospective study. These patients are grouped according to different medication methods, assigned them to receive either tacrolimus plus topical corticosteroids (control group) or dupilumab combined with tacrolimus and topical corticosteroids (study group), with 84 patients in each group. Clinical efficacy and adverse reactions were primary clinical endpoints. RESULTS: The use of dupilumab significantly increased the total effective rate for the patients by 14.29%, from 77.38% (65/84) in the control group to 91.67% (77/84) in the study group. Following treatment, patients given dupilumab showed a more significantly decreased peripheral blood eosinophils (EOS) and immunoglobulin E (IgE) levels than those without dupilumab treatment. Patients administered with dupilumab exhibited markedly lower scores on the Patient-oriented Eczema Measure (POEM) at weeks 12 and 16 and lower Eczema Area and Severity Index (EASI) scores at weeks 8, 12, and 16 when compared to those patients who did not receive dupilumab therapy. At the 16-week, 37 patients in the study group obtained a score of 1/0 on the Verified Investigator's Global Assessment (v-IGA) scale, whereas the control group had 24 such cases, indicating a significantly higher response rate provided by the protocol incorporating dupilumab. After 16 weeks of treatment, both groups demonstrated a marked decrease in itch numeric rating scale (NRS) scores and Dermatology Life Quality Index (DLQI) scores, with lower scores observed in the study group than in the control group. The absence of a significant difference in the incidence of adverse reactions between the two groups suggested a high safety profile of dupilumab. CONCLUSIONS: The combination of dupilumab with topical tacrolimus demonstrated favorable efficacy in the management of AD in children aged 6 to 12 years. This treatment protocol effectively alleviates symptoms, enhances the quality of life of patients, and shows no increased risk of adverse reactions.

[Long-term trend analysis of liver cancer survival rate in Qidong region, Jiangsu Province, 1972-2019].

Objective: To analyze the incidence and survival rate of liver cancer cases in the entire population in the Qidong region from 1972 to 2019, so as to provide a basis for prognosis evaluation, prevention, and treatment. Methods: The observed survival rate (OSR) and relative survival rate (RSR) of 34 805 cases of liver cancer in the entire Qidong region population from 1972 to 2019 were calculated using Hakulinen's method with SURV3.01 software. Hakulinen's likelihood ratio test was used for statistical analysis. Age-standardized relative survival (ARS) was calculated using the International Cancer Survival Standard. The Joinpoint regression analysis was performed with Joinpoint 4.7.0.0 software to calculate the average annual percentage change (AAPC) of the liver cancer survival rate. Results: 1-ASR increased from 13.80% in 1972-1977 to 50.20% in 2014-2019, while 5-ASR increased from 1.27% in 1972-1977 to 27.64% in 2014-2019. The upward trend of RSR over eight periods was statistically significant (χ (2) = 3045.29, P < 0.001). Among them, male 5-ASR was 0.90%, 1.80%, 2.33%, 4.92%, 5.43%, 7.05%, 10.78%, and 27.78%, and female 5-ASR was 2.33%, 1.51%, 3.35%, 3.92%, 3.84%, 7.18%, 11.45%, and 29.84%, respectively. There was a statistically significant difference in RSR between males and females (χ (2) = 45.68, P < 0.001). The 5-RSR for each age group of 25-34 years old, 35-44 years old, 45-54 years old, 55-64 years old, 65-74 years old, and 75 years old were 4.92%, 5.29%, 8.17%, 11.70%, 11.63%, and 9.60%, respectively. There were statistically significant differences in RSR among different age groups (χ (2) = 501.29, P < 0.001). The AAPC in Qidong region from 1972 to 2019 for 1-ARS, 3-ASR, and 5-ARS were 5.26% (t = 12.35, P < 0.001), 8.10% (t = 15.99, P < 0.001), and 8.96 % (t = 16.06, P < 0.001), respectively. The upward trend was statistically significant in all cases. The AAPC of 5-ARS was 9.82% in males (t = 14.14, P < 0.001), and 8.79% in females (t = 11.48, P < 0.001), and the upward trend was statistically significant in both. The AAPC of 25-34 years old, 35-44 years old, 45-54 years old, 55-64 years old, 65-74 years old, and 75 years old were 5.37% (t = 5.26, P = 0.002), 5.22% (t = 5.66, P = 0.001), 7.20% (t = 6.88, P < 0.001), 10.00% (t = 12.58, P < 0.001), 9.96% (t = 7.34, P < 0.001) and 8.83% (t = 3.51, P = 0.013), and the upward trend was statistically significant. Conclusion: The overall survival rate of registered cases of liver cancer in the Qidong region's entire population has greatly improved, but there is still much room for improvement. Hence, constant attention should be paid to the study on preventing and treating liver cancer.

[Long-term trend of gastric cancer survival rate in Qidong, 1972-2016].

Objective: The survival rate of gastric cancer cases in the whole population of Qidong City of Jiangsu Province from 1972 to 2016 was analyzed to provide a data basis for prevention and control of gastric cancer. Methods: The observed survival rate (OSR) was calculated by the life table method, the relative survival rate (RSR) was calculated by SURV 3.01 software, and the trend test was performed by Hakulinen's likelihood ratio test. Age-standardized relative survival rate (ARSR) was calculated using the International Cancer Survival Standard (ICSS). The Joinpoint regression model was used to calculate the average annual percentage change (AAPC) of survival rate, and the trend analysis of the overall survival rate of gastric cancer and the survival rates of different sexes and ages was conducted. The ARIMA model was used to predict the survival rate. Results: From 1972 to 2016, there were 18 067 new cases of gastric cancer in Qidong City. The OSRs at 1, 5, and 10 years were 37.12%, 17.16%, and 12.86%, respectively, and the RSRs at 1, 5, and 10 years were 38.83%, 21.73%, and 21.20%. Dividing 1972-2016 into 9 periods at 5-year intervals, compared with 1972-1976, the 5-year RSR in 2012-2016 increased from 12.53% to 36.26%, and the RSR in the 9 periods increased with statistical significance (χ(2)=747.19, P<0.001). Both OSR and RSR were slightly higher in men than in women, and decreased with age. The AAPC results showed that the AAPC of the 5-year RSR of gastric cancer in Qidong was 2.88%, 2.75% in males and 3.05% in females, and the upward trend was statistically significant (P<0.001). From 1972 to 2016, the 5-year RSR of gastric cancer in all age groups showed an upward trend. Except for the 35-44-year-old group (AAPC=1.07%, t=2.16, P=0.067), the age groups had statistical significance ( AAPC=2.59% in the 45-54-year-old group, AAPC=3.19% in the AAPCs of other 55-64-year-old group, AAPC=3.99% in the 65-74-year-old group, and AAPC=2.97% in the 75-year-old group, all P<0.05). The prediction results of the ARIMA model showed that in 2026, the 5-year OSR of gastric cancer in Qidong will increase to 39.82%, and the 5-year RSR will increase to 49.23%. Conclusion: The overall survival rate of registered gastric cancer cases in Qidong has been greatly improved, but there is still large room for improvement. More attention should be paid to the prevention and treatment of gastric cancer.

[Long-term trend of colorectal cancer survival rate in Qidong, 1972-2016].

Objective: The survival of colorectal cancer in Qidong City, Jiangsu Province from 1972 to 2016 was analyzed to provide a basis for the evaluation of prognosis and the formulation of prevention and control measures. Methods: Colorectal cancer data were obtained from the Qidong Cancer Registration and Reporting System, and the follow-up was up to December 31, 2021. The observed survival rate (OSR) and relative survival rate (RSR) were calculated by SURV 3.01 software, and the trend test was performed by Hakulinen's likelihood ratio test. The Joinpoint regression model was used to calculate the average annual percentage change (AAPC) of survival, and the ARIMA model was used to predict the trend of colorectal cancer survival. Results: There were 8 637 new cases of colorectal cancer in Qidong from 1972 to 2016. Dividing 1972-2016 into 9 periods at 5-year intervals, the 5-year OSR from 1972-1976 to 2012-2016 increased from 21.86% to 48.86%, and the 5-year RSR increased from 26.45% to 59.91%. The increasing trend of RSR was statistically significant (χ(2)=587.47, P<0.001). From 1972 to 2016, the survival rates of colorectal cancer in different sexes in Qidong were similar, and the 5-year RSR was 44.63% for men and 44.07% for women. Since the 1990s, the 5-year OSR and RSR for men have been lower than those for women. From 1972 to 2016, the 5-year RSR of colorectal cancer in Qidong was significantly improved in the 65-74 and ≥75-year-old groups, but the survival rate of the ≥75-year-old group was still the lowest (36.78%), followed by the 35-44-year-old group ( 43.04%). The time trend showed that the overall AAPC of colorectal cancer 5-year RSR in Qidong from 1972 to 2016 was 2.50% (t=16.45, P<0.001). The upward trend of different sexes was consistent, and the increase was greater in women (AAPC for males=2.18%, AAPC for females=2.54%, both P<0.05). The 5-year RSR of colorectal cancer in each age group showed an upward trend, and the AAPCs of the 35-44, 45-54, 55-64, 65-74, and ≥75-year-old groups were 1.54%, 1.83%, 2.00%, 3.51% and 4.35%, respectively (all P<0.05). The prediction results of colorectal cancer survival rate showed that the 5-year RSR of colorectal cancer in Qidong will increase to 71.62% by 2026. Conclusions: The overall survival rate of colorectal cancer patients in Qidong has been greatly improved, but there is still room for improvement. We should continue to pay attention to the early diagnosis and early treatment of colorectal cancer.

[Long-term trend of esophageal cancer survival rate in Qidong, 1972-2016].

Objective: To analyze the survival of esophageal cancer cases in Qidong, Jiangsu Province from 1972 to 2016, and provide a basis for the prognosis evaluation and prevention of esophageal cancer patients. Methods: The data of esophageal cancer were obtained from the Qidong Cancer Registration and Reporting System, and the follow-up date ended December 31, 2021. Observed survival rate (OSR) and relative survival rate (RSR) were calculated by SURV 3.01 software, and Hakulinen's likelihood ratio test was used for statistical difference comparison. Joinpoint regression model was used to conduct the average annual percentage change (AAPC) in esophageal cancer survival rate, and the ARIMA model was used to predict the trend of esophageal cancer survival rate. Results: During 1972 to 2016, there were 5 112 new cases of esophageal cancer in Qidong. The OSR of esophageal cancer at 1, 5 and 10 years were 24.43%, 6.93% and 4.43%, and the RSR at 1, 5 and 10 years were 25.88%, 9.35% and 8.34%, respectively. Dividing 1972-2016 into 9 periods, compared with 1972-1976, the 5-year RSR from 2012-2016 increased from 4.47% to 17.85%, and the RSR trend of the 9 periods was statistically significant (χ(2)=263.43, P<0.001). The survival rate of female with esophageal cancer was slightly higher than that of male, however, there was no significant difference in RSR between male and female (χ(2)=9.40, P=0.401). The 5-OSR and 5-RSR for male were 6.73% and 9.11%, and for female were 7.37% and 9.87%, respectively. The 5-RSR for the age groups of 45-54, 55-64, 65-74, and over 75 years old were 11.99%, 11.21%, 8.17% and 7.08%, respectively. There was a statistically significant difference in RSR among different age groups (χ(2)=98.19, P<0.001). The time trend results showed that the overall AAPC of the 5-RSR of esophageal cancer in Qidong from 1972 to 2016 was 3.89% (t=11.98, P<0.001). The 5-RSR uptrend was consistent among different genders, and the uptrend was greater in female (AAPC=4.25% for male, and AAPC=5.72% for female, P<0.05). Furthermore, the 5-RSR of esophageal cancer in all age groups showed an upward trend, and the upward trend was statistically significant in the 55-64-year-old group (AAPC=4.23%, P<0.05) and the 65-74-year-old group (AAPC=6.82%, P<0.05), there was no statistical significance in the 45-54-year-old group (AAPC=2.17%, P>0.05) and more than 75 years old group (AAPC=1.82%, P>0.05). Survival rate prediction of esophageal cancer showed that by 2026, 5-RSR will increase to 24.79%. Conclusions: During 1972 to 2016, the overall survival rate of esophageal cancer in the whole population of Qidong has improved to a certain extent, but there is still a large room for improvement. More emphasis should be continued to strengthen on the early diagnosis and early treatment of esophageal cancer.

[Epidemic characteristics of esophageal cancer mortality in Qidong, 1972-2016].

Objective: To describe the epidemic characteristics of esophageal cancer mortality in Qidong from 1972 to 2016, and to provide baseline for making control measures and strategies for prevention. Methods: The cancer registry data were collected and analyzed on mortality of oesophagus cancer during 1972-2016 in Qidong in different sex, age and time. Indices of statistics included crude mortality rate (CR), China age-standardized rate (CASR), world age-standardized rate (WASR), 35-64 years truncated rate, 0-74 years cumulative rate, cumulative risk, average annual percentage change (AAPC), mortality by period and mortality in the birth cohort. Results: A total of 4 795 esophageal cancer cases (male: 3 315, female: 1 480) died during the 45 years, accounting for 4.85% of all cancer deaths. The crude mortality was 9.48/10(5) (CASR: 3.62/10(5,) WASR: 6.30/10(5)) from 1972 to 2016. The crude mortality was significantly increased with age. In 2016, the crude mortality was 11.61/10(5) (CASR: 2.64/10(5,) WASR: 4.89/10(5)), respectively. The average annual percentage change (AAPC) were 0.99%、-2.03%、-1.72%. The mortalities of esophageal cancer in all age groups from 35 to 74 have been decreasing since the 1980s. The age-birth cohort analysis showed a decline in mortality rates in age groups from 40 to 79. Conclusions: The crude mortality rate of esophageal cancer increases slightly in Qidong, while the China age-standardized rate and world age-standardized rate decrease significantly. However, esophageal cancer is still one of the malignant tumors that affects the health of residents and seriously threatens the people's lives and health. The situation of cancer prevention and control is still serious in Qidong.

[Correlation analysis of smell and taste loss with COVID-19 outbreak trend based on big data of internet].

Objective: To analyze the correlation between loss of smell/taste and the number of real confirmed cases of coronavirus disease 2019 (COVID-19) worldwide based on Google Trends data, and to explore the guiding role of smell/taste loss for the COVID-19 prevention and control. Methods: "Loss of smell" and "loss of taste" related keywords were searched in the Google Trends platform, the data were obtained from Jan. 1 2019 to Jul. 11 2021. The daily and newly confirmed COVID-19 case number were collected from World Health Organization (WHO) since Dec. 30 2019. All data were statistically analyzed by SPSS 23.0 software. The correlation was finally tested by Spearman correlation analysis. Results: A total of data from 80 weeks were collected. The retrospective analysis was performed on the new trend of COVID-19 confirmed cases in a total of 186 292 441 cases worldwide. Since the epidemic of COVID-19 was recorded on the WHO website, the relative searches related to loss of smell/taste in the Google Trends platform had been increasing globally. The global relative search volumes of "loss of smell" and "loss of taste" on Google Trends was 10.23±2.58 and 16.33±2.47 before the record of epidemic while 80.25±39.81 and 80.45±40.04 after (t value was 8.67, 14.43, respectively, both P<0.001). In the United States and India, the relative searches for "loss of smell" and "loss of taste" after the record of epidemic were also much higher than before (all P<0.001). The correlation coefficients between the trend of weekly new COVID-19 cases and the Google Trends of "loss of smell" in the global, United States, and India was 0.53, 0.76, and 0.82 respectively (all P<0.001), the correlation coefficients with Google Trends of "loss of taste" was 0.54, 0.78, and 0.82 respectively (all P<0.001). The lowest and highest point of loss of smell/taste search curves of Google Trends in different periods appeared 7 to 14 days earlier than that of the weekly newly COVID-19 confirmed cases curves, respectively. Conclusions: There is a significant positive correlation between the number of newly confirmed cases of COVID-19 worldwide and the amount of keywords, such as "loss of smell" and "loss of taste", retrieved in Google Trends. The trend of big data based on Google Trends might predict the outbreak trend of COVID-19 in advance.

Transmutation of long-lived fission products in an advanced nuclear energy system.

Disposal of long-lived fission products (LLFPs) produced in reactors has been paid a lot attention for sustainable and clean nuclear energy. Although a few transmutation means have been proposed to address this issue, there are still scientific and/or engineering challenges to achieve efficient transmutation of LLFPs. In this study, we propose a novel concept of advanced nuclear energy system (ANES) for transmuting LLFPs efficiently without isotopic separation. The ANES comprises intense photoneutron source (PNS) and subcritical reactor, which consist of lead-bismuth (Pb-Bi) layer, beryllium (Be) layer, and fuel, LLFPs and shield assemblies. The PNS is produced by bombarding radioactive cesium and iodine target with a laser-Compton scattering (LCS) γ-ray beam. We investigate the effect of the ANES system layout on transmutation efficiency by Monte Carlo simulations. It is found that a proper combination of the Pb-Bi layer and the Be layer can increase the utilization efficiency of the PNS by a factor of ~ 10, which helps to decrease by almost the same factor the LCS γ-beam intensity required for driving the ANES. Supposing that the ANES operates over 20 years at a normal thermal power of 500 MWt, five LLFPs including 99Tc, 129I, 107Pd, 137Cs and 79Se could be transmuted by more than 30%. Their effective half-lives thus decrease drastically from ~ 106 to less than 102 years. It is suggested that this successful implementation of the ANES paves the avenue towards practical transmutation of LLFPs without isotopic separation.

[Epidemic characteristics of stomach cancer mortality in Qidong during 1972-2016].

Objective: To describe the epidemic characteristics of stomach cancer mortality in Qidong between 1972 and 2016. Methods: The cancer registry data of stomach cancer death and population during 1972-2016 in Qidong was collected. The mortality of crude rate (CR), China age-standardized rate (CASR), world age-standardized rate (WASR), 35-64 years truncated rate, 0-74 years cumulative rate, cumulative risk, percentage change (PC), annual percent change (APC) were calculated. Results: During 1972-2016, a total of 15 863 (male: 10 114, female: 5 749) deaths occurred attributed to stomach cancer, accounting for 16.04% of all cancers, with CR of 31.37/100 000 (CASR: 12.97/100 000, WASR: 21.39/100 000). The truncated rate of 35-64, cumulative rate of 0-74, and cumulative risk were 28.86/100 000, 2.54%, and 2.51%, respectively. For male, the CR, CASR, WASR were 40.53/100 000, 17.98/100 000, 30.13/100 000, respectively, and for female, the CR, CASR, WASR were 22.45/100 000, 8.52/100 000, 13.92/100 000, respectively. Age-specific mortality analysis showed that the mortality of each age group under 25-year-old group was less than 1/100 000. The CR increased with age. The 50-year-old group reached and exceeded the average mortality of the population, and more than 80-year-old group reached the peak of death. During 1972-2016 in Qidong, The PCs in CR, CASR, and WASR of stomach cancer were 55.43%, -52.02%, -43.60%. The APC were 0.54%, -2.30%, -2.08%, respectively. Period mortality analysis showed that except for the 75-year-old group, the mortality of stomach cancer decreased significantly. Conclusions: The crude mortality of stomach cancer increases slightly in Qidong, while the CASR and WASR decrease significantly. However, stomach cancer is still one of the malignant tumors that most affect health and seriously threat lives.

[An analysis of mortality trends for upper gastrointestinal neoplasms in Qidong, 1972-2016].

Objective: To describe the trend of upper gastrointestinal cancer mortality in Qidong between 1972 and 2016, and to provide guidelines for prevention and control measures and strategies. Methods: The upper gastrointestinal data was collected in Qidong cancer registration from 1972 to 2016. Crude mortality rate (CR), China age-standardized rate (CASR), world age-standardized rate (WASR), truncated rate (35-64 years old), cumulative rate (0-74 years old) and cumulative risk were calculated. Annual percent change (APC) was calculated by Joinpoint software. Age-period-cohort model was used to analyze the influence of age, period and birth cohort on the changes in the mortality trend of upper gastrointestinal cancer patients. Results: From 1972 to 2016, there were 20 658 deaths of upper gastrointestinal cancer in Qidong, accounting for 20.89% of all cancer deaths. The CR, CASR, WASR, truncated rate (35-64 years old), cumulative rate (0-74 years old) and cumulative risk were 40.85/100 000, 27.96/100 000, 27.69/100 000, 36.01/100 000, 3.30% and 3.25%, respectively. There were 13 429 male deaths, the CR, CASR, and the WASR were 53.81/100 000, 37.62/100 000, and 39.93/100 000; the female deaths were 7 229, and the CR, CASR, and WASR were 28.23/100 000, 18.87/100 000, 17.25/100 000, respectively. The APCs of the 45-year-old, 55-year-old and 65-year-old age groups were -2.94% (95% CI: -3.32%, -2.56%), -2.94% (95% CI: -3.22%, -2.66%) and -2.04% (95% CI: -2.39%, -1.69%), with significant difference (P<0.05), while without significance of 75-year-old group (P>0.05). From 1972 to 2016, the APCs of CR, CASR, and WASR in the gastrointestinal cancer were 0.65% (95%CI: 0.43%, 0.87%), -2.01% (95%CI: -2.24%, -1.77%) and -2.05% (95%CI: -2.28%, -1.81%). The age-period-cohort model showed that the mortality of upper gastrointestinal cancer was increased with age (P<0.05). Conclusions: The crude mortality of upper gastrointestinal cancer increases slightly in Qidong, while the CASR and WASR decrease significantly. However, with aged tendency of population, the early diagnosis and treatment of upper gastrointestinal cancer is still needed to be paid attention.

[Association of health-related physical fitness with kidney function and lipid profile among faculty in a university].

Objective: To study the association of health-related physical fitness (HPF) with kidney function and blood lipid to provide a basis to prevent chronic diseases and making exercise prescriptions. Methods: This study was conducted in December 2019 with 299 faculty members of a university in Shaanxi, testing HPF indicators (muscle mass, body fat percentage, grip, sit-and-reach, vital capacity) , kidney function indicators (creatinine, uric acid, urea) , and blood lipid indicators[triglyceride (TG) , total cholesterol (TC) , high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) ]. Spearman correlation analysis and binary logistic regression were used to analyze the association between HPF with kidney function and blood lipid indicators. Results: In men, muscle mass and grip strength were positively correlated with uric acid, body fat percentage was positively correlated with TG, sit-and-reach and vital capacity were negatively correlated with TG (r(s)=0.266, 0.337, 0.300, -0.339, -0.239, P<0.05) . In women, body fat percentage was positively correlated with uric acid, TG, TC and LDL-C, negatively correlated with creatinine and HDL-C, grip strength was positively correlated with creatinine, sit-and-reach was positively correlated with HDL-C and negatively correlated with TG, vital capacity was negatively correlated with urea (r(s)=0.240, 0.349, 0.214, 0.249, -0.254, -0.209, 0.186, 0.207, -0.255, -0.154, P<0.05) . Logistic regression showed that high body fat percentage was risk factor for abnormal uric acid and dyslipidemia in female faculty members (OR=1.114, 95%CI:1.023-1.213; OR=1.116, 95%CI: 1.034-1.208; P<0.05) . And high body fat percentage was risk factor for dyslipidemia in male faculty members (OR=1.129, 95%CI: 1.017-1.252, P<0.05) . Conclusion: High body fat percentage is associated with dyslipidemia and uric acid abnormalities in university faculty. HPF fitness assessment may be important for the prevention of chronic diseases related to kidney function or lipids.

[An analysis of mortality trends for lung cancer during 1972-2016 in Qidong city of Jiangsu Province].

Crude mortality rate (CR) for lung cancer in Qidong increased from 11.50/105 in 1972-1976 to 76.61/105 in 2012-2016, China age-standardized rate (CASR) from 13.11/105 in 1972-1976 to 34.27/105 in 2012-2016, and World age-standardized rate (WASR) from 13.40/105 in 1972-1976 to 34.30/105 in 2012-2016. The average annual percentage change (AAPCs) of CR, CASR, WASR were 4.87% (95%CI: 4.63%-5.12%), 2.17% (95%CI: 1.96%-2.38%), 2.12% (95%CI: 1.92%-2.33%) (all P values<0.001), respectively. AAPCs for 45-54, 55-64, 65-74 and over 75 age groups were 0.74% (95%CI: 0.36%-1.11%), 1.23% (95%CI: 0.92%-1.53%), 2.55% (95%CI: 2.20%-2.90%), 4.26% (95%CI: 3.56%-4.96%) (all P values<0.001), respectively.

Gene deficiency and pharmacological inhibition of caspase-1 confers resilience to chronic social defeat stress via regulating the stability of surface AMPARs.

Both inflammatory processes and glutamatergic systems have been implicated in the pathophysiology of mood-related disorders. However, the role of caspase-1, a classic inflammatory caspase, in behavioral responses to chronic stress remains largely unknown. To address this issue, we examined the effects and underlying mechanisms of caspase-1 on preclinical murine models of depression. We found that loss of caspase-1 expression in Caspase-1-/- knockout mice alleviated chronic stress-induced depression-like behaviors, whereas overexpression of caspase-1 in the hippocampus of wild-type (WT) mice was sufficient to induce depression- and anxiety-like behaviors. Furthermore, chronic stress reduced glutamatergic neurotransmission and decreased surface expression of glutamate receptors in hippocampal pyramidal neurons of WT mice, but not Caspase-1-/- mice. Importantly, pharmacological inhibition of caspase-1-interleukin-1ß (IL-1ß) signaling pathway prevented the depression-like behaviors and the decrease in surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in stressed WT mice. Finally, the effects of chronic stress on both depression- and anxiety-like behaviors can be mimicked by exogenous intracerebroventricular (i.c.v.) administration of IL-1ß in both WT and Caspase-1-/- mice. Taken together, our findings demonstrate that an increase in the caspase-1/IL-1ß axis facilitates AMPAR internalization in the hippocampus, which dysregulates glutamatergic synaptic transmission, eventually resulting in depression-like behaviors. These results may represent an endophenotype for chronic stress-induced depression.

Up-regulation of LINC00346 inhibits proliferation of non-small cell lung cancer cells through mediating JAK-STAT3 signaling pathway.

OBJECTIVE: To investigate the expression levels of LINCRNA00346 in tissues and cells in patients with non-small cell lung cancer (NSCLC) and its biological function. PATIENTS AND METHODS: The relative expression levels of LINC 00346 in 70 cases of tissues and cells in NSCLC patients were detected via quantitative reverse transcription polymerase chain reaction (qRT-PCR). The specific interference sequences of LINC 00346 were designed and the transfection efficiency after 48 h was detected. The effect of LINC 00346 on the proliferation capacity of NSCLC cells was studied via cell counting kit-8 (CCK-8) assay. After the interference in LINC 00346 expression in NSCLC cells, the changes in cell cycle and apoptosis were detected via flow cytometry. The nude-mouse transplanted tumor model was established to study the effect of LINC 00346 on in vivo tumorigenic ability of tumor cells. After the interference in LINC 00346 expression, the changes in expressions of molecular markers in the downstream signaling pathway were detected via Western blotting. RESULTS: The LINC 00346 expressions were relatively high in 50 cases of tissues and 5 kinds of tumor cells in NSCLC patients. After the interference in LINC 00346 expression, the apoptosis of tumor cells was promoted, the cell proliferation was inhibited, and the cell cycle was arrested in G1-G0 phase. The animal experiment revealed that the interference in LINC 00346 expression could inhibit the in vivo tumorigenic ability of tumor cells. Western blotting showed that LINC 00346 could exert its function through partially regulating the Janus kinase/signal transducer and activator of transcription 3 (JAK-STAT3) signaling pathway. CONCLUSIONS: The expressions of LINC 00346 were relatively high in NSCLC tissues and cells. LINC 00346 promotes the proliferation and inhibits the apoptosis of NSCLC cells through regulating the JAK-STAT3 signaling pathway.

[Early diagnosis and early treatment for liver cancer in Qidong: survival of patients and effectiveness of screening].

Objective: To evaluate the patients' survival and effectiveness of the live cancer screening for population at high risk for liver cancer in Qidong. Methods: According to the Expert Scheme proposed the Expert Committee of Early Detection and Early Treatment, China Cancer Foundation, diagnostical screening by using combined methods of alpha-fetoprotein and B ultrasound monitoring were carried out biannually in individuals with positive HBsAg who were screened from Qidong area. The evaluation indices of the effectiveness are task completion rate of screening, detection rate of liver cancer, early diagnosis rate, and treatment rate. The deadline of the follow-up for the surviving outcome was March 31, 2016. The life-table method was used to calculate the observed survival, and to make comparison and significant tests between survival rates in Group A (those found via repeated periodic screening) and Group B (those diagnosed without periodic screening). Results: Since 2007, 38 016 target population have been screened, and 3 703(9.74%) individuals with positive HBsAg were found. Except for 29 patients with liver cancer at the initial screening, 3 674 persons in the cohort were followed up; 268 patients with liver cancer were detected from the 33 199 person-times screening, with an annual detection rate of 1.61%. Of them, 186 patients were found in Group A(1.12%), in which 149 patients were the early cases, with an early detection rate of 80.11%; 167 out of 186(89.78%) patients received treatment after diagnosis. The incidence of liver cancer in this HBsAg (+ ) cohort of 25 452 person-years was 1 052.96 per 100 000 annually, 187 cases in males(1 488.45/100 000)and 81 cases in females(628.46/100 000). The 1-, 3-, 5-, and 8-year survival of all patients with liver cancer were 64.55%, 40.50%, 32.54%, and 19.65%, respectively. The 1-, 3-, 5-, and 8-year survival rates were 77.16%, 49.04%, 38.53%, and 24.25% in Group A, and were 36.25%, 21.21%, 21.21%, and 0% in Group B, respectively, with significant differences between two groups (P<0.05). Conclusion: The findings show that screening of individuals at high-risk of development of liver cancer, with semiannual AFP and B ultrasound, according to the Expert Scheme, is effective not only in increasing detection rate but also in detecting liver cancer at early stage, and in improving patients' survival as well.

Impact of E × B shear flow on low-n MHD instabilities.

Recently, the stationary high confinement operations with improved pedestal conditions have been achieved in DIII-D [K. H. Burrell et al., Phys. Plasmas 23, 056103 (2016)], accompanying the spontaneous transition from the coherent edge harmonic oscillation (EHO) to the broadband MHD turbulence state by reducing the neutral beam injection torque to zero. It is highly significant for the burning plasma devices such as ITER. Simulations about the effects of E × B shear flow on the quiescent H-mode (QH-mode) are carried out using the three-field two-fluid model in the field-aligned coordinate under the BOUT++ framework. Using the shifted circular cross-section equilibriums including bootstrap current, the results demonstrate that the E × B shear flow strongly destabilizes low-n peeling modes, which are mainly driven by the gradient of parallel current in peeling-dominant cases and are sensitive to the Er shear. Adopting the much more general shape of E × B shear ([Formula: see text]) profiles, the linear and nonlinear BOUT++ simulations show qualitative consistence with the experiments. The stronger shear flow shifts the most unstable mode to lower-n and narrows the mode spectrum. At the meantime, the nonlinear simulations of the QH-mode indicate that the shear flow in both co- and counter directions of diamagnetic flow has some similar effects. The nonlinear mode interaction is enhanced during the mode amplitude saturation phase. These results reveal that the fundamental physics mechanism of the QH-mode may be shear flow and are significant for understanding the mechanism of EHO and QH-mode.

The relationship between the internal oxidation-reduction system and fetal distress on pregnant patients with intrahepatic cholestasis.

OBJECTIVE: To discuss the relationship between the internal oxidation-reduction system and fetal distress in pregnant patients with intrahepatic cholestasis in order to provide a new basis for clinical treatment and research. PATIENTS AND METHODS: From March 2012 to March 2015, eighty patients with intrahepatic cholestasis of pregnancy (ICP) were selected and divided into two groups: the distressed group (n = 31) and non-distressed group (n = 49). We compared the two groups for differences in MDA, SOD, NO level, GSH level, venous blood and total bile acid level. The relevance of the oxidation-reduction system indicators and the venous blood and total bile acid levels, as well as the differences in the delivery outcome and fetal distress, were compared between the two groups. RESULTS: The serum MDA level of the distressed group was higher than the non-distressed group while the SOD, NO, and GSH levels were lower than the non-distressed group. All differences were statistically significant (p < 0.05). Both the venous blood and total bile acid levels in the distressed group were higher than the non-distressed group and were statistically significant (p < 0.05). Based on Pearson's analysis, MDA was positively associated with the venous blood and total bile acid levels while SOD, NO and GSH levels were negatively associated with it. All differences were statistically significant (p < 0.05). The death rate of cesarean section and perinatal infant in the distressed group were higher than that of the non-distressed group. The proportion of mild and severe asphyxia was higher than the non-distressed group. However, the neonatal weight of the distressed group was lower. All differences were statistically significant (p < 0.05). CONCLUSIONS: The internal oxidation-reduction system indicators of pregnant patients with intrahepatic cholestasis, which are MDA, SOD, NO and GSH levels, may contribute to the occurrence of fetal distress.