The Relationship Between Systemic Lupus Erythematosus and Osteoporosis Based on Different Ethnic Groups: a Two-Sample Mendelian Randomization Analysis.

The previous observational studies could not overcome the effects of confounding variables and reverse causality. We aimed to determine whether there is a causal relationship between systemic lupus erythematosus and osteoporosis in East Asian and European populations, respectively, by two-sample Mendelian Randomization analysis. We obtained and downloaded data from publicly available genome-wide association study databases and analyses for East Asian and European populations, including systemic lupus erythematosus (SLE), osteoporosis (OP), multisite bone mineral density (BMD), and OP with fracture. After screening for instrumental single-nucleotide polymorphisms (SNPs) significantly correlated to SLE, the inverse-variance weighted (IVW) method was used for calculating the ratio and 95% confidence interval, besides utilizing MR-Egger, weighted median, and weighted mode to assess the robustness of the primary outcome. Moreover, multiple analyses, including MR-PRESSO, MR-Egger intercept, Cochran's Q test, as well as "leave-one-out" sensitivity, were used for evaluating horizontal pleiotropy, heterogeneity, and stability. Finally, we exchanged exposure and outcome and performed a reverse MR analysis. IVW (OR = 1.05, 95% CI = 1.01-1.09, P = 0.009) indicated a significant positive correlation between genetically predicted SLE and OP in East Asians. Furthermore, neither heterogeneity nor horizontal pleiotropy was observed. In Europe, there was no significant genetically predicted causal relation between SLE and OP. Bi-directional MR analysis showed no reverse causality between SLE and OP. In the East Asian population, genetically predicted SLE may have had a positive causal relationship with OP. In Europe, there is insufficient evidence for a potential causal relation between SLE and OP or BMD and fracture, and the correlations currently observed may be attributed to a variety of confounder variables.

Dynamics of oxidative stress and immune responses in neonatal calves during diarrhea.

Oxidative stress is the imbalanced redox status between oxidant production and their scavengers leading to intestinal physiological dysfunction. However, the role of systemic and local oxidative status during neonatal calf diarrhea is not known. This study assessed systemic (serum) and local (fecal) oxidative status when calves either naturally developed diarrhea or naturally recovered. Healthy calves were enrolled in the study at d 18 of age, and their health status was monitored from the enrollment. Based on their enteric health status on d 21 and 28, calves were grouped as continuous diarrhea from d 21 to 28 (n = 14), diarrhea at d 21 but recovered at d 28 (DH group, n = 19), healthy at d 21 but developed diarrhea at d 28 (HD group, n = 15), and healthy throughout the study (HH group, n = 16). Serum and fecal samples were collected at d 21 and 28 from all calves in the morning 2 h after feeding. Dynamics of oxidative stress indicators including reactive oxygen species (ROS), malondialdehyde (MDA), H2O2, 8-hydroxy-2'-deoxyguanosine (8-OHDG), glutathione peroxidase, superoxide dismutase, catalase (CAT), and total antioxidant capacity and inflammatory indicators TNF-α, IL-1ß, IL-4, IL-6, IL-10, and IFN-γ were evaluated using serum samples. In addition, fecal oxidative stress indicators ROS and MDA were measured. Serum ROS, MDA, 8-OHDG, as well as fecal ROS and MDA, were higher, whereas serum CAT and H2O2 were lower in diarrheic calves than those of healthy calves. Serum ROS, MDA, and 8OHDG and fecal ROS and MDA increased in the HD group from d 21 to 28 as they developed diarrhea. In contrast, all these oxidative stress markers decreased in the DH group from d 21 to 28 as they recovered. However, serum H2O2 had an opposite changing trend, which became lower in the HD group and higher in the DH group at d 28. In conclusion, both systemic and local oxidative stress markers and cytokine profiles altered as calves moved from being healthy to having diarrhea or vice versa. Serum ROS, MDA, and 8-OHDG can be used to develop biomarkers to screen calves prone to enteric infections during the preweaning period.

[Analysis of the incidence and mortality of thyroid cancer in Shandong Province from 2012 to 2022 based on the age-period-cohort model].

Objective: To analyze the trend of incidence and mortality of thyroid cancer and estimate its age-period-cohort effect in Shandong Province from 2012 to 2022. Methods: The Joinpoint regression was used to analyze the trend of incidence and mortality of thyroid cancer and calculate the average annual percentage change (AAPC) based on the data on thyroid cancer from 2012 to 2022. The age-period-cohort model was used to analyze the age-effect, time-effect and cohort-effect of thyroid cancer risk in the population aged over 20 years. Results: From 2012 to 2022, the incidence of thyroid cancer in Shandong province showed a significant upward trend, with an AAPC of 21.68% (95%CI: 19.14%-24.27%, P<0.001). The incidence of females was higher than that of males, and the incidence of urban areas was higher than that of rural areas. The trend of thyroid cancer mortality was relatively stable with an AAPC of -3.04% (95%CI:-8.81%-3.09%, P=0.323). The age effect of incidence increased with age before 60 years old and decreased with age after 60 years old. The incidence peaked in the age group of 55-59. The period effect increased with time. The cohort effect showed that the cohort born before 1957 had a downward trend over time, while the cohort born after 1957 had an upward trend. Conclusion: The incidence of thyroid cancer in Shandong shows a rising trend from 2012 to 2022. Age is an important factor affecting the risk of thyroid cancer. The mortality of thyroid cancer remains stable.

Identifying canonical and replicable multi-scale intrinsic connectivity networks in 100k+ resting-state fMRI datasets.

Despite the known benefits of data-driven approaches, the lack of approaches for identifying functional neuroimaging patterns that capture both individual variations and inter-subject correspondence limits the clinical utility of rsfMRI and its application to single-subject analyses. Here, using rsfMRI data from over 100k individuals across private and public datasets, we identify replicable multi-spatial-scale canonical intrinsic connectivity network (ICN) templates via the use of multi-model-order independent component analysis (ICA). We also study the feasibility of estimating subject-specific ICNs via spatially constrained ICA. The results show that the subject-level ICN estimations vary as a function of the ICN itself, the data length, and the spatial resolution. In general, large-scale ICNs require less data to achieve specific levels of (within- and between-subject) spatial similarity with their templates. Importantly, increasing data length can reduce an ICN's subject-level specificity, suggesting longer scans may not always be desirable. We also find a positive linear relationship between data length and spatial smoothness (possibly due to averaging over intrinsic dynamics), suggesting studies examining optimized data length should consider spatial smoothness. Finally, consistency in spatial similarity between ICNs estimated using the full data and subsets across different data lengths suggests lower within-subject spatial similarity in shorter data is not wholly defined by lower reliability in ICN estimates, but may be an indication of meaningful brain dynamics which average out as data length increases.

[Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis].

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

[Reliability and validity of the Chinese version of adverse childhood experiences international questionnaire in parents of preschool children].

OBJECTIVE: To test the reliability and validity of the Chinese version of adverse childhood experiences international questionnaire (ACE-IQ) in Chinese parents of preschool children. METHODS: The parents of preschool children in 6 kindergartens in Tongzhou District of Beijing were selected by stratified random cluster sampling, and the Chinese version of ACE-IQ after translation and adaptation was used for survey online. The collected data were randomly divided into two parts. One part of the data (n=602) was used for exploratory factor analysis (EFA), to screen items and evaluate structural validity, and then form the final Chinese version of ACE-IQ. The other part of the data (n=700) was used for confirmatory factor analysis (CFA), criterion validity analysis and reliability analysis. At the same time, experts investigation method was used to evaluate the content validity of the final Chinese version of ACE-IQ. RESULTS: After deleting four items of collective violence, the Chinese version of ACE-IQ with twenty-five items indicated good structural, criterion and content validity. Analysis results showed that the Chinese version of ACE-IQ presented a seven-factor model dimension, namely emotional neglect, physical neglect, family dysfunction, family violence, emotional and physical abuse, sexual abuse and violence outside the home, and the total score of the binary version of ACE-IQ Chinese version was positively correlated with the total score of childhood trauma questionaire-28 item short form (CTQ-SF, r=0.354, P < 0.001) and the center for epidemiological studies depression scale (CES-D, r=0.313, P < 0.001) respectively. Results from five experts showed that the item-level content validity index (I-CVI) of 25 items was between 0.80 and 1.00, and the average of all I-CVIs on the scale (S-CVI/Ave) of the scale was 0.984. At the same time, the internal consistency (Cronbach's α coefficient) of the whole scale was 0.818, and the split-half reliability (Spearman-Brown coefficient) was 0.621, which demonstrated good reliability. CONCLUSION: This study has formed a Chinese version of ACE-IQ with 25 items and 7 dimensions, which has good reliability and validity among the parents of preschool children in China. It can be used as an evaluation instrument for measuring the minimum threshold of the adverse childhood experiences in the parents of preschool children in the cultural background of China.

[Reference values for carotid artery intima-media thickness among community adult dwellers in Shenzhen City].

Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was meanCIMT=0.324 7+0.006 9×age and SDCIMT=0.076 9+0.001 2×age. For women, the regression was meanCIMT=0.354 9+0.005 4×age and SDCIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.

[Bronchial tuberculosis complicated with massive hemorrhage after Dieulafoy's disease biopsy: a case report].

Compared with simple bronchial Dieulafoy's disease, bronchial tuberculosis with Dieulafoy's disease is rarer and more complex, with non-specific clinical manifestations. In this article, we reported a case of right lateral basal segment bronchial tuberculosis complicated with Dieulafoy's disease. The clinical manifestations, microscopic features, and rescue procedures in the event of massive hemorrhage in this case were described in detail, and the shortcomings in the clinical diagnosis and treatment of this case were analyzed. The aim of this study was to improve clinicians' understanding of bronchial tuberculosis combined with Dieulafoy's disease.

[Analysis of the prevalence of dyslipidemia and correlative factors in Tajik population in Pamir Plateau of Xinjiang].

Objective: To investigate the prevalence of dyslipidemia and the level of blood lipids among Tajik people in Pamir Plateau, Xinjiang, and explore the related factors of dyslipidemia. Methods: It is a retrospective cross-sectional study. A multi-stage cluster random sampling survey was conducted among 5 635 Tajiks over 18 years old in Tashkorgan Tajik Autonomous County, Xinjiang Province from May to October 2021. Data were collected through questionnaire survey (general information, medical history, and personal history), physical examination (height, weight, waist, and blood pressure) and blood test (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density cholesterol (HDL-C)) to analyze the dyslipidemia and its risk factors among Tajiks. Results: The age of Tajik participants was (41.9±15.0) years, including 2 726 males (48.4%). The prevalence of borderline high TC, high LDL-C and high TG levels were 17.2%, 14.7% and 8.9%, respectively. The prevalence of high TC, high LDL-C, high TG and low HDL-C were 4.1%, 4.9%, 9.4% and 32.4%, respectively, and the prevalence of dyslipidemia was 37.0%. There is a positive correlation between male,higher education level, higher body mass index (BMI) value,waist circumference, living in town, smoking and dyslipidemia. Conclusions: The low prevalence of high TC, high LDL-C, high TG and high prevalence of low HDL-C was a major characteristic of Tajik people in Pamir Plateau of Xinjiang. The lower rates of overweight and obesity may be one of the reasons for the lower prevalence of dyslipidemia among Tajik.

Moving beyond the 'CAP' of the Iceberg: Intrinsic connectivity networks in fMRI are continuously engaging and overlapping.

Resting-state functional magnetic resonance imaging is currently the mainstay of functional neuroimaging and has allowed researchers to identify intrinsic connectivity networks (aka functional networks) at different spatial scales. However, little is known about the temporal profiles of these networks and whether it is best to model them as continuous phenomena in both space and time or, rather, as a set of temporally discrete events. Both categories have been supported by series of studies with promising findings. However, a critical question is whether focusing only on time points presumed to contain isolated neural events and disregarding the rest of the data is missing important information, potentially leading to misleading conclusions. In this work, we argue that brain networks identified within the spontaneous blood oxygenation level-dependent (BOLD) signal are not limited to temporally sparse burst moments and that these event present time points (EPTs) contain valuable but incomplete information about the underlying functional patterns. We focus on the default mode and show evidence that is consistent with its continuous presence in the BOLD signal, including during the event absent time points (EATs), i.e., time points that exhibit minimum activity and are the least likely to contain an event. Moreover, our findings suggest that EPTs may not contain all the available information about their corresponding networks. We observe distinct default mode connectivity patterns obtained from all time points (AllTPs), EPTs, and EATs. We show evidence of robust relationships with schizophrenia symptoms that are both common and unique to each of the sets of time points (AllTPs, EPTs, EATs), likely related to transient patterns of connectivity. Together, these findings indicate the importance of leveraging the full temporal data in functional studies, including those using event-detection approaches.

Effect of pathological complete response after neoadjuvant chemoradiotherapy on postoperative complications of rectal cancer: a systematic review and meta-analysis.

BACKGROUND: Standard total mesorectal resection has become an important treatment option for locally advanced or high-risk rectal cancer after neoadjuvant chemo-radiotherapy. 15-27% of patients can achieve pathological complete response (PCR) after neoadjuvant chemo-radiotherapy (nCRT). However, the relationship between PCR and postoperative complications remains an important unsolved problem. The objective of this study was to determine whether PCR was associated with the rate of postoperative complications. METHODS: This meta-analysis was implemented following the recommendations from Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We searched electronic literature by PubMed, EMBASE, and Google Scholar. Major outcomes of interest included anastomotic leakage, surgical-site infection, reoperation, and any postoperative complications. Other outcomes comprised postoperative hemorrhage, ileus, and mortality. RESULTS: Eleven thousand two hundred ninety patients in 9 studies were included in the meta-analysis. The pooled analysis revealed that patients with PCR did not have a higher risk of anastomotic leakage (OR = 1.22, 95% CI 0.92-1.62, p = 0.17), reoperation (OR = 1.13, 95% CI 0.93-1.37, p = 0.22), and any postoperative complications (OR = 1.02, 95% CI 0.91-1.15, p = 0.72) than patients with non-PCR. However, the meta-analysis showed that the PCR group was superior to the non-PCR group in terms of surgical-site infection (9.38% vs. 12.44%OR = 0.68, 95% CI 0.47-0.98; p = 0.04). CONCLUSION: PCR might not be related to the occurrence of postoperative complications in rectal cancer patients following nCRT. In addition, PCR might be associated with a lower risk of surgical-site infection.

[Preliminary exploration of the metabolic profile and metabolic pathways in newly diagnosed multiple myeloma].

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.

[Deep learning-assisted construction of three-demensional facial midsagittal plane].

OBJECTIVE: To establish a deep learning algorithm that can accurately determine three-dimensional facial anatomical landmarks, multi-view stacked hourglass convolutional neural networks (MSH-CNN) and to construct three-dimensional facial midsagittal plane automatically based on MSH-CNN and weighted Procrustes analysis algorithm. METHODS: One hundred subjects with no obvious facial deformity were collected in our oral clinic. Three-dimensional facial data were scanned by three-dimensional facial scanner. Experts annotated twenty-one facial landmarks and midsagittal plane of each data. Eighty three-dimensional facial data were used as training set, to train the MSH-CNN in this study. The overview of MSH-CNN network architecture contained multi-view rendering and training the MSH-CNN network. The three-dimensional facial data were rendered from ninety-six views that were fed to MSH-CNN and the output was one heatmap per landmark. The result of the twenty-one landmarks was accurately placed on the three-dimensional facial data after a three-dimensional view ray voting process. The remaining twenty three-dimensional facial data were used as test set. The trained MSH-CNN automatically determined twenty-one three-dimensional facial anatomical landmarks of each case of data, and calculated the distance between each MSH-CNN landmark and the expert landmark, which was defined as position error. The midsagittal plane of the twenty subjects' could be automatically constructed, using the MSH-CNN and Procrustes analysis algorithm. To evaluate the effect of midsagittal plane by automatic method, the angle between the midsagittal plane constructed by the automatic method and the expert annotated plane was calculated, which was defined as angle error. RESULTS: For twenty subjects with no obvious facial deformity, the average angle error of the midsagittal plane constructed by MSH-CNN and weighted Procrustes analysis algorithm was 0.73°±0.50°, in which the average position error of the twenty-one facial landmarks automatically determined by MSH-CNN was (1.13±0.24) mm, the maximum position error of the orbital area was (1.31±0.54) mm, and the minimum position error of the nasal area was (0.79±0.36) mm. CONCLUSION: This research combines deep learning algorithms and Procrustes analysis algorithms to realize the fully automated construction of the three-dimensional midsagittal plane, which initially achieves the construction effect of clinical experts. The obtained results constituted the basis for the independent intellectual property software development.

[The expression and clinical significance of long non-coding RNA GIHCG in cholangiocarcinoma].

Objective: To screen long non-coding RNA (lncRNA) related to the prognosis of cholangiocarcinoma patients, detect its expression in cholangiocarcinoma tissue, and analyze its clinical significance by analyzing The Cancer Genome Atlas (TCGA) database. Methods: Using limma package, survival package, and survival receiver operating characteristic curve (ROC) package of R software to analyze the data of cholangiocarcinoma in TCGA and screen the differentially expressed lncRNAs related to patient survival. Real-time PCR and Fish were used to detect the expression of lncRNA and analyze its correlation with the clinical characteristics of patients. Small interfering RNA was used to knock down the expression of lncRNA GIHCG, and its effect on the migration ability of cholangiocarcinoma cell lines was detected by Transwell. Results: The results of the comprehensive analysis of survival, ROC, and correlation analysis with clinical data showed that lncRNA GIHCG has a significant correlation with lymph node metastasis in patients with cholangiocarcinoma. The expression of lncRNA GIHCG in cholangiocarcinoma tissue is significantly increased, closely related to tumor size and lymph node metastasis. Transwell results showed that lncRNA GIHCG could promote the migration of cholangiocarcinoma cells. Conclusion: The expression of lncRNA GIHCG is significantly increased in cholangiocarcinoma tissues and is closely related to patient survival and lymph node metastasis. It is expected to become a new molecular marker for diagnosing or treating cholangiocarcinoma.

[Cancer survival during 2012-2018 in cancer registries of Shandong Province].

Objective: To analyze the 5-year cancer relative survival rate in cancer registries of Shandong Province during 2012-2018. Methods: 399 072 new cancer cases were collected in 23 cancer registries in Shandong Province during 2012-2018. All malignant tumors (C00-C97, D45-D47), benign central nervous system tumors (D32-D33), and central nervous system tumors (D42-D43) were registered according to the 10th revision of international classification of diseases (ICD). The survival of cancer patients was obtained by passive and active follow-up. The follow-up date was December 31, 2020. The diagnostic years were divided into three periods: 2012-2014, 2015-2017 and 2018-2020. The 5-year cancer survival rates were calculated by cohort approach, period analysis and hybrid approach, and the survival status of different sex, urban and rural areas, cancer species and age groups were analyzed. Results: The age of 399 072 new cancer cases was (63.5±13.7) years old, with 57.77% (230 538 cases) about male and 32.89% (131 247 cases) from urban. During 2012-2014, 2015-2017 and 2018-2020, the 5-year cancer survival rates in Shandong Province were 32.3%, 34.7% and 40.2%, respectively. In 2018-2020, the first five cancers with survival rates were thyroid cancer (86.0%), breast cancer (78.2%), testicular cancer (75.7%), bladder cancer (70.3%) and uterine cancer (69.2%), and the last five cancers with survival rates were pancreatic cancer (15.5%), liver cancer (16.8%), gallbladder cancer (19.6%), bone cancer (22.7%) and lung cancer (24.4%). The 5-year survival rate for cancer of women (47.8%) was higher than that of men (33.8%), and the rate of urban areas (45.7%) was higher than that of rural areas (37.3%) during 2018-2020. The first five cancers in men were thyroid (87.1%), testicular (75.7%), bladder (70.9%), kidney (65.6%) and prostate (62.8%) cancers, and the last five cancers were pancreatic (14.3%), liver (16.8%), gallbladder (18.2%), bone (19.9%) and lung (21.7%) cancers. The first five cancers in women were thyroid (85.5%), breast (78.0%), uterine (69.2%), bladder (68.8%) and kidney (66.8%) cancers, and the last five cancers were liver (17.2%), pancreatic (17.2%), gallbladder (22.0%), bone (27.2%) and lung (29.1%) cancers. Conclusion: The 5-year cancer survival rate in Shandong Province was on the rise from 2012 to 2018, and the survival rates of different cancers were different.

[Spatio-temporal trend of female breast cancer mortality in Shandong Province from 1970 to 2013].

The mortality of female breast cancer in Shandong Province has increased since the 1970. The differential decomposition analysis found that the slight decline in the crude mortality of breast cancer among women was entirely due to non-demographic factors during the 1970-1990, and the significant increase in the crude mortality was due to a combination of demographic and non-demographic factors since the 1990. The contribution rate of demographic factor has gradually increased from 53.5% in 2004-2005 to 59.5% in 2011-2013, while that of non-demographic factor has decreased from 46.5% to 40.5%. The women aged 45-64 years old were the major population of female breast cancer deaths, accounting for 40%-60% of total breast cancer deaths in different times, and then the mortality in female aged 55-64 years old increased rapidly, with increases of 52.12%, 115.19% and 29.01% in 2011-2013 over the 1970-1974, 1990-1992 and 2004-2005, respectively (Z=-7.342,P<0.001). Compared with 1970-1974, the age-standardized mortality rate of rural women increased by 41.86% in 2011-2013 (Z=-17.933, P<0.001), and that of urban women increased by 18.62% in 2011-2013 (Z=-25.642, P<0.001). The age-standardized mortality rate of breast cancer in urban women was higher than that in rural women in different times (all P<0.05). The spatial scan analysis found that eastern Shandong Province was found to be a sustained high-risk area for death, and other high-risk areas were transferred from north to southwest of Shandong between 1970 and 2013.

[Mortality level and tendency of road traffic injury in Shandong Province from 2012 to 2020].

Objective: To analyze the mortality level and tendency of road traffic injury in Shandong province from 2012 to 2020. Methods: Based on the data of road traffic deaths from the cause of death registration system in Shandong province from 2012 to 2020, the mortality rates of road traffic injury were calculated by sex, age, area, and injury type. The mortality was standardized based on the age structure of the Chinese population in the sixth Population Census in 2010. The annual percent change (APC) and average annual percent change (AAPC) of the mortalities and the standarized mortalities were calculated by using Joinpoint regression model, and the trends were also examined. Results: In 2020, the crude mortality of road traffic injury in Shandong Province was 15.58/100 000, and the standardized mortality was 12.90/100 000. From 2012 to 2020, the standardized mortality of road traffic injury in Shandong province showed a downward trend with AAPC of -5.4%. The standardized mortality of middle-south mountain areas, male and children aged 0-14 years in Shandong showed a significantly decreasing trend with AAPC of -6.8%, -6.1% and -6.0%, respectively. The standardized mortality of people aged 65 years and over did not decrease significantly, but the number of deaths increased significantly by 50.96% in 2020 (5 780 cases), compared with those in 2012 (3 829 cases). The standardized mortality of pedestrian and motorcyclists decreased significantly with AAPC of -7.5% and -6.7%, respectively. There was no significant change in the standardized mortality among people who rode motor vehicles or bicycles. Conclusion: From 2012 to 2020, the standardized mortality of road traffic injury in Shandong Province showed an obvious downward trend, but the standardized mortality of people aged 65 years and over did not decrease significantly. In the future, it is still necessary to take government-led, multi-sectoral collaboration, with a focus on comprehensive preventive measures, to further reduce road traffic injury mortality.

[Sorafenib regulates vascular endothelial growth factor by runt-related transcription factor-3 to inhibit angiogenesis in hepatocellular carcinoma].

Objective: To investigate the molecular mechanism of sorafenib against hepatocellular carcinoma. Methods: Sorafenib efficacy was screened and verified by the hepatocellular carcinoma patient-derived tumor xenograft (PDX) model. Veterinary B-mode ultrasonography and in vivo confocal laser scanning microscopy were used to observe PDX angiogenesis. Immunohistochemistry was used to observe the expression of proliferation and angiogenesis-related proteins in PDX tissue. Real-time quantitative PCR technology was used to observe the RUNX3 gene in PDX tissues. SPSS 17.0 statistical software was used for statistical analysis. Results: Four cases of PDX were used to screen the efficacy of sorafenib. PDX1 had a significant response to sorafenib, with an inhibition rate of 68.07%. Compared with the control group, sorafenib had significantly inhibited PDX1 relative tumor volume (5.76±2.14 vs. 11.71±2.87, P<0.05). Cell division index (39.50±7.72 vs. 67.10±9.14, P<0.05) and Ki67 expression (288.6±43.40 vs. 531.70±55.60, P<0.05) were significantly decreased. Veterinary B-mode ultrasonography showed evident blood flow signals in PDX1 tumors. In vivo confocal laser scanning microscopy results showed that sorafenib had significantly reduced the total vessel length (1573.00±236.21 vs. 2675.03±162.00, P<0.05) and area (11 145.33±1931.97 vs. 20 105.37±885.93, P<0.05)) of PDX1 tumors. Immunohistochemical results showed that sorafenib had significantly down-regulated the protein expressions of CD34 (27.55±3.76 vs. 45.47±5.57, P<0.05), VEGF (16.33±2.86 vs. 22.77±3.20, P<0.05) and MVD (38.75±6.01 vs. 55.50±8.61, P<0.05). Real-time PCR results showed that sorafenib had significantly up-regulated RUNX3 gene expression (2.14±0.71 vs. 1.00±0.36, P<0.05). However, there was a negative correlation between the expression of RUNX3 gene and the ratio of VEGF-positive cells in sorafenib group (R2=0.509 7). Conclusion: Sorafenib may inhibit the PDX angiogenesis and the growth of hepatocellular carcinoma by regulating the RUNX3-VEGF pathway.

[Mechanical circulatory support combined with immunomodulation treatment for patients with fulminant myocarditis: a single-center real-world study].

Objective: To investigate the relationship between the mechanical circulatory support (MCS) combined with immunomodulation and the prognosis of patients with fulminant myocarditis. Methods: This is a retrospective study. A total of 88 patients with fulminant myocarditis admitted to Dongguan Kanghua hospital from Aug. 2008 to Dec. 2020 were included. Medical histories, results of laboratory tests, treatment regimens and clinical outcomes of these patients during their hospitalization were collected from the medical record system. According to the treatment methods, the patients were divided into MCS+immunomodulation group (38 cases), MCS group (20 cases) and traditional treatment group (30 cases). Patients in the MCS+immunomodulation group received intra-aortic balloon pump (IABP) or IABP combined with extracorporeal membrane oxygenation (ECMO) and immunoglobulin or glucocorticoid. Patients in the MCS group only received mechanical circulatory support. Patients in the traditional treatment group received neither mechanical circulatory support nor immunomodulatory therapy, and only used vasoactive drugs and cardiotonic drugs. The in-hospital mortality and length of stay were compared among the three groups. Results: A total of 88 patients with fulminant myocarditis aged (35.0±10.8) years were included, and there were 46 males (52.3%). The mortality of MCS+immunomodulation group (7.9% (3/38) vs. 56.7% (17/30), P=0.001 2) and MCS group (30.0% (6/20) vs. 56.7% (17/30), P=0.002 8) were lower than that of traditional treatment group. Compared with the MCS group, the in-hospital mortality in the MCS+immunomodulation group was lower (P=0.005 4). The most common cause of death was multiple organ dysfunction syndrome (MODS). The constituent ratios of death in MCS+immunomodulation group, MCS group and traditional treatment group were 3/3, 4/6 and 12/17, respectively. The incidence of MODS in the MCS group (20% (4/20)) and the traditional treatment group (40% (12/30)) was significantly higher than that in the MCS+immunomodulation group (7.9% (3/38)) (both P<0.01). In discharged patients, the hospitalization time of MCS+immunomodulation group was shorter than that of traditional treatment group ((13.4±5.5)d vs. (18.5±7.4)d, P<0.05) and MCS group ((13.4±5.5)d vs. (16.9±8.5)d, P<0.05). Conclusion: MCS combined with immunomodulatory therapy is associated with lower in-hospital mortality and shorter hospital stay in patients with fulminant myocarditis.

ASSOCIATION BETWEEN THE CTLA-4 EXON 1+49A/G POLYMORPHISM AND THE RELAPSE OF GRAVE'S DISEASE AFTER ATD WITHDRAWAL: A META-ANALYSIS.

Background: The cytotoxic T lymphocyte-associated molecules-4 (CTLA-4) is related to the relapse of Graves' disease (GD) after anti-thyroid drugs (ATDs) withdrawal. We performed a meta-analysis to generate large-scale evidence on whether the CTLA-4 exon 1+49A/G polymorphism can predict the relapse of GD after ATDs withdrawal. Methods and Results: The PubMed, EMBASE,the Cochrane Library and reference lists of relevant studies were searched to identify eligible studies from inception to Jan, 2021. Ten eligible studies consisting of 1450 GD patients with a total of 848 relapsed patients were included in the meta-analysis.In Caucasians patients, the CTLA-4 exon 1+49A/G polymorphism significantly elevated the relapse risk of GD in additive (OR = 2.07, 95% CI: 1.18-3.62, P=0.011), dominant (OR = 2.52, 95% CI: 1.17-5.41, P=0.02), homozygote model(OR = 3.264, 95% CI: 1.25-8.52, P=0.016), except recessive (OR = 2.18, 95% CI = 0.98-4.86, P = 0.062) and heterozygote model (OR = 2.141, 95% CI = 0.958-4.786, P = 0.064). In Asian subgroup, none of these genotypes show any associations with the relapse of GD after ATDs withdrawal. Conclusion: This meta-analysis suggests that the CTLA-4 exon1 +49A/G polymorphism is associated with the relapse risk of GD after ATDs withdrawal in Caucasians, not Asians. Compared with the AA genotype, Caucasian patients with GG genotype have 3.264 times risk of relapse. A more aggressive treatment such as radioactive iodine or thyroidectomy, or longer periods treatment of ATDs should be recommended in Caucasian patients with the GG genotype.