BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population

ObjectiveTo explore the effects of astragalin （AST） on autophagy and apoptosis of astrocytes in the L_4-5 dorsal horn of the spinal cord in mice with inflammatory pain induced by complete Freund's adjuvant （CFA）. MethodsTwenty-four male C57BL/6 mice， aged six months， were randomly assigned to four groups： control group， saline group， CFA model group， and CFA+AST group， six mice in each group. The inflammatory pain model was established by injection of 10 µL CFA into the right lateral malleolus fossa. The saline group were injected with an equal amount of normal saline at the same site. The inflammatory pain mice in CFA+AST group were further treated with AST （60 mg/kg） intraperitoneally once a day for 21 consecutive days. Multiplex immunofluorescence staining was used to detect the coexpression of autophagy-related factors including ATG 12 and Beclin-1， apoptosis-related factors including Cleaved-Caspase3 and Caspase9， and the astrocyte marker such as GFAP in the L_4-5 spinal dorsal horn of the mice in each group. Western blot was used to examine the protein expression levels of autophagy-related proteins（ATG12， Beclin-1） and apoptosis-related proteins（Caspase 3， Caspase 9） in the L_4-5 spinal dorsal horn of mice. ResultsImmunofluorescent staining showed that in the L_4-5 dorsal horn of the spinal cord， the fluorescence intensity of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） was significantly increased， while that of Cleaved-Caspase 3 （P<0.001） and Caspase 9 （P<0.000 1） was decreased in the CFA+AST group when compared to the CFA model group. Furthermore， AST could inhibit the activation of astrocytes. Western blot further confirmed that AST significantly upregulated the expression of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） in the L_4-5 spinal cord of CFA mice， and downregulated the expression of Caspase 3 （P<0.01） and Caspase 9 （P<0.001）. ConclusionsAST promotes autophagy of astrocytes and inhibits their apoptosis in the L_4-5 spinal dorsal horn of CFA mice.

ObjectiveTo investigate the potential value of thyroid hormones in cerebrospinal fluid in predicting autism-like behaviors induced by hypothyroidism in pregnant rats. MethodsTwelve pregnant Wistar rats were randomly divided into a control group and a hypothyroidism group （hypothyroidism model group）. Offspring from both groups had serum and cerebrospinal fluid levels of thyroid-stimulating hormone （TSH）， total triiodothyronine （TT3）， total thyroxine （TT4）， free triiodothyronine （FT3）， and free thyroxine （FT4） levels in serum and cerebrospinal fluid. Ultrasonic vocalization tests were conducted on postnatal day 2 （P2）， day 7 （P7）， and day 14 （P14）， while behavioral tests using the three-box social interaction test were performed on day 21（P21）. ResultsCompared with the control group， free T4 （FT4） levels in the cerebrospinal fluid of the hypothyroidism group were significantly reduced during the developmental period （P0-P21； P2： P<0.05； P7： P<0.05； P14： P<0.01； P21： P<0.01）， with no statistical difference between the two groups only at P0 （P>0.05）. In the ultrasonic vocalization （USV） tests， the number and duration of USVs in offsprings from the hypothyroidism group were significantly reduced compared with those of the control group on P2， P7 and P14： for USV counts （P2： P<0.05； P7： P<0.001； P14： P<0.01）； for USV duration （P2： P<0.05； P7： P<0.001； P14： P<0.001）. In the three-box social tests， offsprings of the hypothyroidism group showed significantly reduced sniffing time with unfamiliar rats at P21 compared to the control group （all P<0.001）. The FT4 levels in cerebrospinal fluid had a significantly positive correlation with USV counts （P7： r=0.883， P<0.05； P14： r=0.902， P<0.05） and sniffing time with unfamiliar rats （r=0.814， P<0.01）. ConclusionMeasuring free T4 in cerebrospinal fluid can predict autism-like behaviors in offsprings of rats induced by hypothyroidism during pregnancy.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Baitouweng Decoction is a classic prescription commonly used in the treatment of heat-toxin dysentery,with confirmed efficacy in the treatment of ulcerative colitis(UC).Clinical studies have found that Baitouweng Decoction,modified Baitouweng Decoction,combined with other Chinese materia medica or other therapies for UC can improve the clinical symptoms of patients,reduce the lesion activity score under colonoscopy,promote the healing of intestinal mucosal tissue,and also improve the overall efficiency of treatment,and reduce adverse reactions and recurrence rate.Pharmacological studies showed that Baitouweng Decoction may treat UC by regulating the expressions of related inflammatory factors and signaling pathways,regulating immune function,repairing intestinal mucosal barrier,and improving intestinal flora imbalance.This article systematically reviewed the clinical and basic research progress of Baitouweng Decoction in the treatment of UC,in order to provide a basis for relevant research.

Objective To investigate the correlation between abdominal obesity and autoimmune thyroid disease in the view point of helper T cells and cytokines.Methods Clinical and laboratory data were collected from 108 pa-tients with Hashimoto's thyroiditis(HT)plus abdominal obesity and 122 patients of Hashimoto's thyroiditis without abdominal obesity who visited the People's Hospital of Xinjiang Uygur Autonomous Region and also from the control population.Abdominal circumference was measured,and patients in the HT patients were grouped according to whether they were abdominally obese or not.The thyroglobulin antibody(TgAb)and thyroid peroxidase antibody(TPOAb)were detected,and the ratio of helper T cells and related cytokines were detected by flow cytometry and enzyme-linked immunosorbent assay.Results The abdominal circumference of the TgAb-positive group was higher than that of the TgAb-negative group(P＜0.05).Correlation analysis suggested that abdominal circumference was significantly and positively correlated with TgAb and IL-4 but negatively correlated with Th1.After correcting for gender and age,and abdominal obesity and IL-4 were risk factors for TgAb antibody positivity OR=3.080(95％CI:1.022-9.284)and OR=1.296(95％CI:1.022-9.284),both with P＜0.05.Conclusions Abdominal obesity may be an influential factor in TgAb antibody positivity,with larger abdominal circumference having higher TgAb antibody titers,lower Th1 levels,and higher IL-4 levels.Visceral adiposity may exacerbate autoimmune dam-age of thyroid tissue by disruption of helper T cell pathway.

Congenital heart disease (CHD) is the most common birth defect worldwide. Long non-coding RNAs (lncRNAs) have been implicated in many diseases. However, their involvement in CHD is not well understood. This study aimed to investigate the role of dysregulated lncRNAs in CHD. We used Gene Expression Omnibus data mining, bioinformatics analysis, and analysis of clinical tissue samples and observed that the novel lncRNA SAP30-2:1 with unknown function was significantly downregulated in damaged cardiac tissues from patients with CHD. Knockdown of lncRNA SAP30-2:1 inhibited the proliferation of human embryonic kidney and AC16 cells and decreased the expression of heart and neural crest derivatives expressed 2 (HAND2). Moreover, lncRNA SAP30-2:1 was associated with HAND2 by RNA immunoprecipitation. Overall, these results suggest that lncRNA SAP30-2:1 may be involved in heart development through affecting cell proliferation via targeting HAND2 and may thus represent a novel therapeutic target for CHD.
Basic Helix-Loop-Helix Transcription Factors ; Cell Proliferation ; Heart Defects, Congenital/genetics* ; Histone Deacetylases ; Humans ; RNA, Long Noncoding/genetics* ; Transcription Factors

Objective:To investigate the effects of different phototherapy intensities on the levels of malondialdehyde, a peroxidation product of intralipid, vitamin C and vitamin E in parenteral nutrition for premature infants.Methods:The parenteral nutrition for premature infants was prepared under strict aseptic condition and was divided into four groups based on different phototherapy intensities in simulated clinical settings, which were indoor light group, single-, double-, and three-sided phototherapy group. According to whether the nutrient solution shielded for light or not, each group was further divided into two subgroups: exposure or non-exposure group. The levels of malondialdehyde, vitamin C and vitamin E in all groups before phototherapy and 6, 12, 18, and 24 h after phototherapy were measured. Ten samples of parenteral nutrient solutions were prepared for each group, of which 2 ml were extracted for test at different time points. Repeated measurement analysis of variance was used for data analysis and the results were adjusted using Greenhouse-Geisser method if failed in Mauchly sphere test.Results:With the increase of phototherapy time, the malondialdehyde level increased in the exposure and the non-exposure subgroups in the one-sided phototherapy group [before phototherapy: (3.777±0.112) vs (3.746±0.141) nmol/ml; phototherapy for 6 h: (3.808±0.122) vs (3.715±0.145) nmol/ml; 12 h: (4.546±0.138) vs (4.507±0.136) nmol/ml; 18 h: (6.116±0.151) vs (5.239±0.156) nmol/ml; 24 h: (7.569±0.136) vs (5.300±0.200) nmol/ml; all P<0.05], but the level of vitamin C [before phototherapy: (62.507±0.205) vs (62.341±0.144)μg/ml; phototherapy for 6 h: (51.211±0.086) vs (58.128±0.076) μg/ml; 12 h: (43.288±0.084) vs (55.351±0.050) μg/ml; 18 h: (35.758±0.113) vs (51.215±0.093) μg/ml; 24 h: (33.473±0.075) vs (48.473±0.080)μg/ml] and vitamin E decreased [before phototherapy: (4.101±0.132) vs (4.084±0.141) μg/ml; phototherapy for 6 h: (3.761±0.119) vs (3.904±0.075) μg/ml; 12 h: (3.654±0.092) vs (3.729±0.087) μg/ml; 18 h: (3.385±0.102) vs (3.582±0.119) μg/ml; 24 h: (3.313±0.127) vs (3.438±0.113) μg/ml, all P<0.05]. The same situation was also observed in indoor light group, double-, and three-sided phototherapy groups. The malondialdehyde level at different time in the exposure subgroups were higher but the vitamin C and vitamin E levels were lower than those in the non-exposure subgroups, regardless of the phototherapy intensities (all P<0.001). (2) The analysis of all exposure phototherapy subgroups showed that the higher the intensity of light therapy, the higher the malondialdehyde level, and the lower the level of vitamin C and vitamin E, with statistical significance differences in any pairwise comparison. Analysis of all non-exposure subgroups showed statistically significant differences in the malondialdehyde level in any pairwise comparison (all P<0.05) except for the comparison between indoor light group and single-sided phototherapy group ( F=2.383. P=0.140). Moreover, the greater the phototherapy intensities, the lower vitamin C level, with statistically significant differences in any pairwise comparison. And statistical significance differences were observed in the vitamin E level in any pairwise comparison (all P<0.05) except for the comparison between double- and three-sided phototherapy groups ( F=1.358, P=0.259). Conclusions:Phototherapy can increase the malondialdehyde level in parenteral nutrient solution for premature infants and the degree of intralipid peroxidation, but can also lead to vitamin C and vitamin E loss in the parenteral nutrient and weaken its antioxidant capacity.

Objective:To explore the value of soluble growth stimulation expression gene 2 protein (soluble suppression of tumorigenicity 2; sST2) and N terminal B type brain natriuretic peptide (N-terminal probrainnatriuretic peptide, NT-proBNP) in evaluating the short-term prognosis of acute organophosphorus pesticide poisoning.Methods:select 228 patients with acute organophosphorus pesticide poisoning in our hospital from October 2017 to March 2020. According to the grade of poisoning degree, it was divided into 82 cases in mild and moderate group and 146 cases in severe group. hs-cTnI、CK-MB、sST2、NT-proBNP、APACHE Ⅱ score and cholinesterase activity were detected 4 h、12 h、24 h after admission. ROC curve was used to evaluate sST2 and NT-proBNP to predict the prognosis of AOPP.Results:4 hours after admission, there was no significant difference in the scores of hs-cTnI, APACHE Ⅱ, cholinesterase and CK-MB between the Severe Group and the mild and moderate Group ( P<0.05) . At 12 and 24 hours after admission, the scores of hs-cTnI, CK-MB and APACHE Ⅱ in severe group were higher than those in mild and moderate group, and the changes of Cholinesterase were more significant than those in 12 hours after Admission ( P<0.05) . 4 hours after admission, SST2 and NT-proBNP levels were significantly higher in severe group than those in mild and moderate Group ( P<0.05) . The level of SST2 and NT-proBNP in the severe group was significantly higher than that in the mild and moderate group 12 and 24 hours after Admission ( P<0.01) , and the level of SST2 and NT-proBNP was significantly higher than that in the mild group 12 hours after Admission ( P<0.05) . Correlation analysis showed that 24 hours after admission, sST2, NT-proBNP were positively correlated with APACHE-Ⅱ scores ( R=0.634, 0.723, P<0.01) . The area under sST2 combined with NT-proBNP was 0.891, higher than that under sST2 and NT-proBNP at 12 h after admission. The 24 h APACHE Ⅱ score after admission area under the curve was 0.838. Conclusion:sST2 and NT-proBNP combined detection can early predict the occurrence of recent complications in AOPP patients.

Objective:To study the real-world outcome of China FDA-approved Sofosbuvir (SOF)/Velpatasvir (VEL) in Northwest China.Methods:In this multicenter, prospective, real-world cohort study, we recruited patients from 10 sites from Northwest China, who were chronically infected with HCV GTs 1-6 from 06/2018 to 09/2019. Patients received SOF (400mg)/VEL (100mg) for 12 weeks, and with ribavirin 900-1200 mg for GT3 cirrhosis and for any genotype decompensated cirrhosis. The primary endpoint was sustained virological response at 12-weeks post-treatment (SVR12) and safety. The secondary endpoint was the change of liver function after the achievement of SVR12.Results:Totally, 143 patients were enrolled in the study, four patients were lost to follow-up and one died during the follow-up, 138 patients were included in per-protocol analysis. Of the 138 patients, the mean age 53 years, 53.6% male, 94.2% Han nationality, 53.6% liver cirrhosis, 10.1% HBsAg +, 6.5% renal dysfunction, 5.1% treatment-experienced, and 16.7% patients received ribavirin treatment. The genotype distribution was as follows: 35.5% GT1, 42.8% GT2, 15.9% GT3, and 5.8% un-typed. The SVR12 rate was 96.5% (138/143, 95% CI: 93.5%-99.6%) for intention-to-treat analysis, and in per-protocol analysis, all 138 patients obtained SVR12 (100%). Compared with baseline, the serum total bilirubin, ALT and AFP levels decreased (all P < 0.05), as well as increased ALB and platelet count (all P < 0.001) at post-treatment 12-weeks. Overall adverse events (AEs) rate is 29.0%, and the most common AEs were anemia (14.5%) and fatigue (8.0%). Severe side effects (edema and fatigue) occurred in 2 patients, one of whom needed a short-term interruption of treatment due to fatigue. Conclusion:In this real-world cohort study, 12-week SOF/VEL regimen with or without ribavirin achieved high SVR12 rates (96.5%-100% overall) with excellent safety profile among patients with HCV GT1/2/3 infection including patients with GT3 and cirrhosis, and led to improvement of liver function.