Perceived Overload on Short Video Platforms and Its Influence on Mental Health Among the Elderly: A Moderated Mediation Model.

Background: In the post-epidemic era, the problem of short-video app addiction among older adults has become increasingly prominent, and people have begun to pay attention to the negative emotional and psychological consequences of Perceived Overload of short-video apps. Given the growing mental health concerns of older adults, it is critical to understand the potential relationship between the Perceived Overload of short video apps for older adults and older adults' mental health. Methods: This study applied the stress-strain-outcome (SSO) framework to explore the relationship between perceived overload of a short-video application and loneliness, mental health, and Confucianism tenets in 1300 Chinese older adults. The relationship between perceived overload and loneliness, mental health, and Confucianism tenet moderated mediation models of perceived overload and mental health were created using SPSS 26.0 and PROCESS 4.1 for SPSS. Results: The perceived overload of a short video application for older adults directly predicted loneliness and mental health in older adults, and the Confucianism tenet moderated the mediation process between perceived overload and mental health. Perceived overload affects mental health through loneliness in older adults. Discussion: The results of this study are of practical significance for understanding the current problem of short-video addiction among older adults. Understanding the effects of perceived overload on older adults' loneliness and mental health can help prevent loneliness and mental health problems caused by short-video addiction among older adults on the one hand, and on the other hand, it can also help to develop targeted coping strategies and create psychological intervention programs based on the Confucianism tenet of intervention ethics to improve mental health in a changing technological stress environment.

Prenatal echocardiography diagnosis of a novel combination of bilateral ductus arteriosus and cardiovascular anomalies: a case report and literature review.

Background: Bilateral ductus arteriosus (BDA) is a relatively rare vascular malformation. According to the double arch theory, BDA is formed when the distal ends of the sixth pairs of primitive arches on the left and right sides have not regressed. We describe a fetus with prenatal echocardiographic findings of BDA and right aortic arch mirror-image branching (RAA-MIB) combined with congenital heart disease. Furthermore, to gain a deeper understanding of the embryological mechanism of BDA, we review the literature on all combinations of BDA present in 40 fetuses/infants. Case summary: A 22-year-old female patient underwent fetal echocardiography at 23 weeks of gestation. Both the two-dimensional (2D) grayscale image and color Doppler flow imaging (CDFI) revealed dextro-transposition of the great arteries combined with a ventricular septal defect and RAA-MIB. The following scan revealed a rare vascular ring, which was identified as BDA extending from the confluent of the left pulmonary artery and right pulmonary artery, completely encircling the trachea to form an "O"-shaped vascular ring before finally converging into the descending aorta. A persistent left superior vena cava was also observed. We subsequently used four-dimensional (4D) color Doppler imaging with the spatiotemporal image correlation (STIC) HD live flow and STIC HD live flow silhouette mode to clearly display ventricular arterial connectivity and the direction of vessel travel. Adjusting the image quality and display angle is very important when applying STIC. The 4D images confirmed our diagnosis. After multidisciplinary counseling and discussion with her family, this female patient decided to terminate the pregnancy. Conclusion: Our review of the literature summarized nine combinations classified into three types of BDA and aortic arch pathology. However, our case differs because it is a novel combination of intracardiac structural abnormalities and vascular rings in a fetus. Prenatal ultrasound diagnosis of BDA is important and requires a combination of 2D grayscale, CDFI, and STIC images to assist in scanning.

Progress in the treatment of advanced hepatocellular carcinoma with immune combination therapy.

Advanced hepatocellular carcinoma (HCC) is a severe malignancy that poses a serious threat to human health. Owing to challenges in early diagnosis, most patients lose the opportunity for radical treatment when diagnosed. Nonetheless, recent advancements in cancer immunotherapy provide new directions for the treatment of HCC. For instance, monoclonal antibodies against immune checkpoint inhibitors (ICIs) such as programmed cell death protein 1/death ligand-1 inhibitors and cytotoxic t-lymphocyte associated antigen-4 significantly improved the prognosis of patients with HCC. However, tumor cells can evade the immune system through various mechanisms. With the rapid development of genetic engineering and molecular biology, various new immunotherapies have been used to treat HCC, including ICIs, chimeric antigen receptor T cells, engineered cytokines, and certain cancer vaccines. This review summarizes the current status, research progress, and future directions of different immunotherapy strategies in the treatment of HCC.

Comparing Safety and Efficacy of TACE + Apatinib in Combination with a PD-1 Inhibitor versus a Non-triple Therapy for Treating Advanced Primary Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: This meta-analysis was performed to compare the efficacy and safety of a triple therapy, involving transcatheter arterial chemoembolization (TACE) + apatinib combined with a programmed-cell death protein-1 (PD-1) inhibitor versus TACE + apatinib, a dual therapy with apatinib and PD-1 inhibitor, and TACE alone for the treatment of advanced primary hepatocellular carcinoma (HCC). METHODS: A computerized systematic search of databases, such as PubMed, Embase, the Cochrane Library, CNKI, Wanfang Data, and VIP e-Journals was performed to retrieve studies comparing TACE + apatinib combined with a PD-1 inhibitor versus a non-triple therapy for the treatment of advanced primary HCC. The literature search, quality assessment, and data extraction were performed independently by two researchers. Stata 16.0 software was employed to analyze the data. Heterogeneity was assessed utilizing the I2 statistic and p-value, followed by conducting sensitivity analysis. RESULTS: A total of 2,352 patients were enrolled from 8 studies, including 900 patients in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor, 877 patients in the TACE + apatinib group, 52 patients in the apatinib + a PD-1 inhibitor group, and 112 patients in the TACE group. The results revealed that the objective response rate (ORR) was significantly higher in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor than that in the non-triple therapy group [odds ratio (OR)=2.47, 95% confidence interval (95%CI): 1.61-3.78]. Besides, disease control rate (DCR) was greater in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor than that in the non-triple therapy group (OR=1.87, 95%CI: 1.44-2.44). Patients in the triple therapy group experienced a significant extension of overall survival (OS) (HR=0.42, 95%CI: 0.36-0.49). In addition, there was no significant difference in the overall rate of adverse events (AEs) between the two groups (OR=1.05, 95%CI: 0.89-1.22). CONCLUSIONS: Compared with the non-triple therapy group, the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor outperformed in terms of tumor response and long-term survival with manageable AEs.

Pre-gravid body mass index is associated with a higher risk of gestational hypertension in singleton pregnancy following frozen-thawed embryo transfer.

Introduction: Although it is well-known that obesity increases the risk of gestational hypertension (GH) in both spontaneous and assisted reproductive technology (ART) pregnancies. Recent data show that, in ART pregnancies, frozen-thawed embryo transfer (FET) is associated with an even higher risk of GH compared with fresh transfer. However, the relationship between pre-gravid body mass index (BMI) and GH in FET pregnancies has seldom been reported. Objective: The aim of this study is to examine the effect of pre-gravid BMI on GH in singleton pregnancy following FET. Methods: A retrospective cohort study at a tertiary hospital, including a total of 7,502 women who achieved singleton pregnancy after FET, was included. All patients were enrolled only once. On the basis of the BMI definitions of the Working Group on Obesity in China (WGOC) and the World Health Organization, the women were divided into normal BMI, overweight, and obese groups. The main outcome was GH, and the effect of pre-pregnancy BMI on GH was assessed by generalized linear model. Results: The risk of GH in our study population was 6.15%. According to the BMI definitions of the WGOC, the risk of GH in the obese group (15.55%) was significantly higher than that of the overweight group (8.26%, P < 0.001) and the normal BMI group (4.68%, P < 0.001). Pre-gravid overweight and obesity were associated with higher GH risk (OR, 1.77; 95% CI, 1.41-2.20; P < 0.001; OR, 3.69; 95% CI, 2.77-4.91; P < 0.001). A non-linear relationship between pre-gravid BMI and GH was observed. The risk of GH decreased with pre-gravid BMI level up to the turning point of BMI = 28.6 kg/m2 (OR, 1.16; 95% CI, 1.12-1.21; P < 0.001). Conclusion: Pre-gravid overweight and obesity are associated with higher GH risk among singleton pregnancy following FET. Before the turning point of BMI = 26.8 kg/m2, the risk of GH may increase 16.4% with each one-unit increment of maternal BMI. Women preparing for FET should maintain a normal BMI to lower the chances of GH.

Who may benefit from an increased gonadotropin dosing in predicted poor responders undergoing IVF/ICSI? A secondary analysis assessing treatment selection markers of a randomized trial.

OBJECTIVE: To evaluate whether we can identify patient characteristics that serve as treatment selection markers to distinguish which women with expected poor response benefit from increased dosing of follicle-stimulating hormone (FSH) in terms of improving the cumulative live birth rate compared to standard FSH dosing and which women. STUDY DESIGN: We performed a secondary analysis of an RCT performed between March 2019 and October 2021 comparing cumulative live birth after increased dosing (N = 328) who received 225 or 300 IU/day according to their antral follicle count (AFC) and standard dosing (N = 333) who received 150 IU/day of gonadotropin. RESULTS: The MFPI analysis showed the benefit of the increased dosing of FSH on cumulative live birth starts to emerge when women were older than 30 years (women > 30 years: 46.5 % vs. 34.2 %; adjusted relative risk (aRR) 1.32, 95 % confidence interval (95 %CI) 1.05-1.66; women ≤ 30 years: 54.7 % vs. 58.6 %; aRR 0.91, 95 % CI 0.72-1.14; p for interaction 0.019). Only those who had AFC between 1 and 3 benefited from the increased FSH dose (AFC 1-3: 38.5 % vs. 6.5 %; aRR 5.88, 95 % CI 1.50-23.15; AFC 4-9: 50.3 % vs. 46.0 %; aRR 1.08, 95 % CI 0.92-1.27; p for interaction 0.023). Expected poor responders defined by the Bologna criteria and POSEIDON criteria did not significantly benefit from the increased dosing of FSH. CONCLUSIONS: Women who are aged >30 years or have AFC 1-3 are likely to benefit from increased dosing of FSH by having a higher cumulative live birth rate.

Establishment of a prediction model for histological chorioamnionitis and its association with outcomes of premature infants.

Aim: This study aims to construct a prediction model for histological chorioamnionitis (HCA) and analyze the associations between the predicted risk of HCA and adverse outcomes in preterm infants. Methods: In total, 673 subjects were included in this cohort study and divided into HCA group (n = 195) and non-HCA group (n = 478). A stepwise method was used to screen the predictors for HCA, binary logistic regression was used to construct the prediction model, and the associations between the predicted risk of HCA and adverse outcomes were analyzed. Results: HCA occurred in 195 patients, accounting for 29.0%. The sensitivity of the prediction model was 0.821 [95% confidence interval (CI): 0.767-0.874)], the specificity was 0.684 (95% CI: 0.642-0.726), the positive predictive value was 0.514 (0.459-0.570), the negative predictive value was 0.903 (95% CI: 0.873-0.934), the area under the curve was 0.821 (95% CI: 0.786-0.855), and the accuracy was 0.724 (95% CI: 0.690-0.757). The predicted risk of HCA was associated with a higher risk of bronchopulmonary dysplasia (BPD) [odds ratio (OR) = 3.48, 95% CI: 1.10-10.95)], sepsis (OR = 6.66, 95% CI: 2.17-20.43), and neonatal infections (OR = 9.85, 95% CI: 3.59-26.98), but not necrotizing enterocolitis (OR = 0.67, 95% CI: 0.24-1.88), retinopathy of prematurity (OR = 1.59, 95% CI: 0.37-6.85), and brain damage (OR = 1.77, 95% CI: 0.82-3.83). After adjusting for confounders including gestational week at birth and birth weight, the risk of neonatal infections (OR = 5.03, 95% CI: 2.69-9.41) was increased in preterm infants' exposure to HCA. Conclusion: The model showed good predictive performance for identifying pregnant women with a higher risk of HCA. In addition, HCA was associated with the risk of BPD, sepsis, and infections in neonates.

Nonlinear Relationship Between Maternal and Cord Blood Vitamin B12 and Folate from a Chinese Population-Based Study.

Purpose: There remains a data gap on vitamin B12 and folate level in maternal and child populations. This study aimed to assess the status of vitamin B12 and folate in maternal serum (MS) and umbilical cord serum (UCS). Materials and Methods: This was a planned secondary analysis of a case-control study. A total of 858 pregnant women during late pregnancy and their newborns in the hospitals of China were included. Maternal peripheral venous blood and neonatal umbilical cord blood were collected to determine serum vitamin B12 and folate concentration. Relationship of vitamin B12 or folate concentration between MS and UCS was assessed by a quantile regression model and the non-linear relationship between them was examined. Results: Nutritional status of serum folate was better than that of vitamin B12. Prevalence of deficiency in MS vitamin B12 and folate was 73.4% and 14.2%, respectively and these figures were about 17.8% and 0.1% in UCS. Both vitamin B12 and folate levels in UCS were significantly higher than those in MS (vitamin B12: 321.0 pg/mL vs 158.3 pg/mL, folate: 16.5 ng/mL vs 7.0 ng/mL, P <0.001). The median UCS-MS ratio of vitamin B12 and folate was 2.0 (95% CI: 1.94-2.06) and 2.4 (95% CI: 2.30-2.53), respectively. The levels of folate and vitamin B12 in UCS increased nonlinearly with their increase in MS which presented an inverted U-shaped curve. Conclusion: Deficiency in vitamin B12 and folate in the women during late pregnancy in China is prevalent. Nutritional status of the two vitamins in umbilical cord serum is correlated nonlinearly with that in maternal serum. Folic acid supplementation may be accompanied with vitamin B12 to improve status of vitamin B12 and folate during pregnancy.

The Interactions between Maternal Iron Supplementation and Iron Metabolism-Related Genetic Polymorphisms on Birth Outcomes: A Prospective Study in Chinese.

BACKGROUND: The effect of iron supplementation during pregnancy on birth outcomes may vary with maternal genetic background and needs more investigation. OBJECTIVES: This prospective study aimed to evaluate the interactions between maternal iron supplementation and iron metabolism-related genetic polymorphisms on birth outcomes. METHODS: This was a substudy from a community-based randomized control trial conducted in Northwest China, which included 860 women from the 2 micronutrient supplementation groups (folic acid [FA] and FA + iron group). Maternal peripheral blood, sociodemographic and health-related information, and neonatal birth outcomes were collected. Six single nucleotide polymorphisms in iron metabolism-related genes were genotyped. The alleles associated with decreased iron/hemoglobin status were used as the effect alleles. The genetic risk score (GRS) that reflected the genetic risk of low iron/hemoglobin status was estimated using the unweighted and weighted methods. Generalized estimating equations with small-sample corrections were applied to evaluate the interactions between iron supplementation and SNPs/GRS on birth outcomes. RESULTS: There were significant interactions between maternal iron supplementation and rs7385804 (P = 0.009), rs149411 (P = 0.035), rs4820268 (P = 0.031), the unweighted GRS (P = 0.018), and the weighted GRS (P = 0.009) on birth weight. Compared with FA supplementation only, FA + iron supplementation significantly increased birth weight among women with more effect alleles in rs7385804 (ß: 88.8 g, 95% CI: 9.2, 168.3) and the GRSs (the highest unweighted GRS, ß: 135.5 g, 95% CI: 7.7, 263.4; the highest weighted GRS, ß: 145.9 g, 95% CI: 43.4, 248.5); it had a trend of decreasing birth weight and increasing low birth weight risk among women with fewer effect alleles. CONCLUSIONS: In our population, maternal genetic background related to iron metabolism plays a significant role in determining the efficacy of iron supplementation. Routine iron supplementation could be more beneficial to fetal weight growth among mothers with higher genetic risk for low iron/hemoglobin status.

Safety and Efficacy of TACE + Lenvatinib in Treating Advanced Hepatocellular Carcinoma: A Systematic Review and Meta- analysis.

BACKGROUND AND AIMS: To compare the efficacy and safety of transarterial chemoembolization (TACE) + lenvatinib (TACE+L) versus lenvatinib (L) monotherapy in the treatment of advanced hepatocellular carcinoma by a meta-analysis. METHODS: PubMed, Embase, the Cochrane Library, CNKI, VIP e-Journals Database, and Wanfang Data were systematically searched to collate literature comparing TACE+L with L alone for the treatment of advanced liver cancer. The literature search, quality assessment, and data extraction were performed independently by two reviewers. The Stata 16 software package was used to process and analyze the data. We assessed heterogeneity using both I2 and the p-value, performed a publication bias assessment, and conducted a sensitivity analysis. RESULTS: Five studies were finally included, including one randomized controlled study and four retrospective studies; these involved a total of 1,167 patients, including 523 patients in the TACE+L combination group and 644 patients in the L monotherapy group. In this meta-analysis, the TACE+L group showed a significantly better objective response rate (ORR) (OR=2.54, 95%CI: 1.34 - 4.80) and disease control rate (DCR) compared to the L monotherapy group (OR=2.68, 95%CI: 1.75 - 4.08). The combined group had significantly improved progression-free survival (PFS) (HR=0.47, 95%CI: 0.40 - 0.56) and overall survival (OS) (HR=0.48, 95%CI: 0.39-0.59). In addition, there was no significant difference found in the overall adverse events of any grade between the two groups (OR=1.13, 95%CI: 0.99 - 1.29). CONCLUSIONS: Compared to L alone, TACE+L treatment resulted in better tumor response, better long-term survival, and was accompanied by controllable adverse events.

Transarterial Chemoembolization plus Apatinib with or without Camrelizumab for the Treatment of Advanced HBV-related Hepatocellular Carcinoma.

AIMS: To compare the effectiveness and safety of transarterial chemoembolization (TACE) combined with apatinib plus camrelizumab (TACE+AC) versus TACE combined with apatinib alone (TACE+A) for patients with advanced HBV-related hepatocellular carcinoma (HBV-HCC). METHODS: The clinical data of patients with HBV-HCC who received either TACE+AC or TACE+A treatment were retrospectively analyzed. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were compared between the two groups. Multivariate Cox proportional hazards model regression analysis was used to identify the independent prognostic factors of OS. RESULTS: Between March 2019 to January 2022, 76 patients were assigned to the TACE+AC group (n = 37) and the TACE+A group (n=39). The median OS and PFS in the TACE+AC group were significantly longer than those in the TACE+A group (OS, 15.4 vs. 11.3 months; p=0.008; PFS, 7.4 vs. 5.1 months; p=0.001) and the ORR and DCR in the TACE + AC group were significantly greater than those in the TACE+A group (ORR, 43.2% vs. 20.5%; p=0.033; DCR, 67.6% vs. 43.6%; p=0.036). There was no significant difference in the incidence of grade ≥3 AEs between the two groups (p=0.483). Multivariate regression analysis identified the treatment modalities, AFP level, and extrahepatic metastasis as independent prognostic factors (p<0.05). CONCLUSION: TACE+AC significantly improved the clinical outcomes of patients with HBV-HCC and elicited relatively controllable AEs.

Cytotoxicity of 4 Wild Mushrooms in a Case of Yunnan Sudden Unexplained Death.

OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS: The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

Effect of increased gonadotropin dosing on maternal and neonatal outcomes in predicted poor responders undergoing IVF: follow-up of a randomized trial.

OBJECTIVE: To evaluate, in women scheduled for IVF with predicted poor ovarian response, the effect of increased dosing of gonadotropin on maternal and neonatal outcomes compared with standard dosing. STUDY DESIGN: We performed a follow-up study of an open-labelled randomized controlled trial comparing increased (225 or 300 IU/d) versus standard (150 IU/d) dose gonadotrophins on cumulative live birth rates. We randomized 661 women with a predicted poor ovarian response (based on their antral follicle count) scheduled for their first IVF/ICSI cycle. Here, we report on maternal and neonatal outcomes between increased and standard dosing groups. RESULTS: There was a trend of increased risk of gestational diabetes mellitus in the increased gonadotrophin dose group compared with the standard group in both cumulative live birth pregnancies (14.8% vs. 7.8%, relative risk (RR) 1.90, 95% confidence interval (CI) 0.96-3.74, P = 0.06) and live birth pregnancies in the first transfer (15.2% vs. 7.7%, RR 1.98, 95 %CI 0.93-4.19, P = 0.08), without reaching statistical significance. The occurrence of gestational diabetes mellitus was significantly higher in the increased gonadotrophin dose group (24/149, 16.1% vs. 8/128, 6.3%; risk ratio (RR) 2.58, 95 %CI 1.19 to 5.54, P = 0.02) in singleton pregnancies. In women with first embryo transfer cycle, maternal hypothyroidism occurred also more frequent in the increased gonadotrophin dose group than the standard group (16.0% vs. 6.8%, RR 2.34, 95 %CI:1.07-5.11, P = 0.03). CONCLUSIONS: In women with predicted poor ovarian response, increased dosing of gonadotropin may result in an increased risk of gestational diabetes mellitus and maternal hypothyroidism.

Maternal exposure to housing renovation during the periconceptional period and the risk of offspring with isolated congenital heart disease: a case-control study.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent birth defect in recent decades. The aim of this research was to examine the association between maternal housing renovation exposure during the periconceptional period and isolated congenital heart disease (CHD) in their offspring. METHODS: A multi-hospitals case-control study was conducted from six tertiary A hospitals in Xi'an, Shaanxi, Northwest China based on questionnaires and interviews to address this question. The cases included fetuses or newborns diagnosed with CHD. Controls consisted of healthy newborns without birth defects. In total, 587 cases and 1180 controls were enrolled in this study. The association between maternal periconceptional housing renovation exposure and isolated CHD for offspring was assessed by estimating odds ratios (OR) with multivariate logistic regression models. RESULTS: After adjusting for potential confounding variables, it was found that maternal exposure to home improvement projects was associated with a higher probability of isolated CHD in offspring (adjusted OR: 1.77, 95% CI: 1.34, 2.33). Additionally, the risk of the ventricular septal defect (VSD) and patent ductus arteriosus (PDA) for CHD types was significantly associated with maternal exposure to housing renovations (VSD: adjusted OR = 1.56, 95% CI: 1.01, 2.41; PDA: adjusted OR = 2.50, 95% CI: 1.41, 4.45). CONCLUSIONS: Our study suggests that maternal exposure to housing renovation during the periconceptional period was associated with an increased risk of isolated CHD in offspring. Consequently, it would be beneficial to avoid living in a renovated home from 12 months before pregnancy through the first trimester to lower isolated CHD in infants.

Hormone replacement treatment regimen is associated with a higher risk of hypertensive disorders of pregnancy in women undergoing frozen-thawed embryo transfer.

Introduction: In frozen-thawed embryo transfer (FET) cycles, hormone replacement treatment (HRT) was associated with a higher risk of hypertensive disorders of pregnancy (HDP) compared with natural cycles (NC). Multiple pregnancy was a risk factor for HDP and several studies did not conduct subgroup analysis of singleton pregnancy and multiple pregnancy. Objective: To investigate whether HRT regimen could be a risk factor for HDP in women undergoing FET cycles in singleton and twin pregnancies. Methods: A retrospective cohort study at a tertiary hospital, including a total of 9120 women who underwent FET and achieved ongoing pregnancy; 7590 patients underwent HRT-FET and 1530 NC-FET. The main outcome was HDP. HDP were analyzed for singleton and twin pregnancies, respectively. Results: In the singleton pregnancy, the risk of HDP in the HRT-FET group was significantly higher than that in the NC-FET group (6.21% vs. 4.09%; P=0.003). After adjusting for female age oocyte pick up, female age at FET and body mass index (BMI), HRT was found as a risk factor for HDP (adjusted odds ration [aOR]: 1.43; 95% confidence interval [CI]: 1.07 to 1.91; P=0.017). In the multiple pregnancy, the risk of HDP in the HRT-FET and NC-FET groups was similar. Conclusion: HRT was associated with a higher risk of HDP in women who underwent FET and achieved singleton pregnancy.

Whole exome sequencing with a focus on cardiac disease-associated genes in families of sudden unexplained deaths in Yunnan, southwest of China.

OBJECTIVES: To explore the causes of sudden unexpected death (SUD) and to search for high-risk people, whole exome sequencing (WES) was performed in families with SUDs.  METHODS: Whole exome sequencing of 25 people from 14 SUD families were screened based on cardiac disease-associated gene variants, and their echocardiograms and electrocardiograms (ECG) were also examined. The protein function of mutated genes was predicted by SIFT, PolyPhen2 and Mutation Assessor. RESULTS: In the group of 25 people from 14 SUD families, 49 single nucleotide variants (SNVs) of cardiac disease-associated genes were found and verified by Sanger sequencing. 29 SNVs of 14 cardiac disorder-related genes were predicted as pathogens by software. Among them, 7 SNVs carried by two or more members were found in 5 families, including SCN5A (c.3577C > T), IRX4 (c.230A > G), LDB3 (c.2104 T > G), MYH6 (c.3G > A), MYH6 (c.3928 T > C), TTN (c.80987C > T) and TTN (c.8069C > T). 25 ECGs were collected. In summary, 4 people had J-point elevation, 2 people had long QT syndrome (LQTS), 4 people had prolonged QT interval, 3 people had T-wave changes, 3 people had sinus tachycardia, 4 people had sinus bradycardia, 4 people had left side of QRS electrical axis, and 3 people had P wave broadening. Echocardiographic results showed that 1 person had atrial septal defect, 1 person had tricuspid regurgitation, and 2 people had left ventricular diastolic dysfunction. CONCLUSIONS: Of the 14 heart disease-associated genes in 14 SUDs families, there are 7 possible pathological SNVS may be associated with SUDs. Our results indicate that people with ECG abnormalities, such as prolonged QT interval, ST segment changes, T-wave change and carrying the above 7 SNVs, should be the focus of prevention of sudden death.

Association between Maternal Blood Glucose Levels during Pregnancy and Birth Outcomes: A Birth Cohort Study.

OBJECTIVE: This study aimed to investigate the relationship between maternal blood glucose levels during pregnancy and neonatal birth outcomes in Northwest China. METHODS: This population-based cohort study included 10,010 first-trimester pregnant women who joined the birth cohort of the Northwest Women's and Children's Hospital from July 2018 to July 2020. Basic demographic characteristics, lifestyle and behavior patterns were collected. Oral glucose tolerance test (OGTT) results during the second trimester and pregnancy outcomes after childbirth were also collected. A generalized linear model was constructed to analyze the effects of blood glucose levels on neonatal birth outcomes. RESULTS: We found that every 1 mmol/L increase in fasting plasma glucose (FPG) was associated with an increase in birth weight (ß = 100.22 g, 95% confidence interval (95%CI): 81.91, 118.52), birth weight Z score (ß = 0.23, 95%CI: 0.19, 0.27) and birth weight Z centile (ß = 6.72%, 95%CI: 5.51, 7.94). Moreover, the risk of macrosomia, premature birth and being born large for gestational age (LGA) increased by 2.01 (95%CI: 1.67, 2.43), 1.35 (95%CI: 1.09, 1.66) and 1.80 (95%CI: 1.57, 2.07) times, respectively. Additionally, for every 1 mmol/L increase in FPG associated with a decrease in gestational age (ß = -0.12 weeks, 95%CI: -0.19, -0.06), the risk of SGA decreased by 0.70 (OR = 0.70, 95%CI: 0.55, 0.89) times. Every 1 mmol/L increase in 1/2-h PG had similar outcomes as FPG, besides premature birth and SGA. CONCLUSIONS: Higher blood glucose in pregnant women may increase neonatal birth weight, decrease gestational age and lead to a higher risk of macrosomia, premature birth and LGA. Mothers should actively prevent and control hyperglycemia to promote maternal and infant health.

Review on Stress-Fractional Plasticity Models.

Fractional calculus plays an increasingly important role in mechanics research. This review investigates the progress of an interdisciplinary approach, fractional plasticity (FP), based on fractional derivative and classic plasticity since FP was proposed as an efficient alternative to modelling state-dependent nonassociativity without an additional plastic potential function. Firstly, the stress length scale (SLS) is defined to conduct fractional differential, which influences the direction and intensity of the nonassociated flow of geomaterials owing to the integral definition of the fractional operator. Based on the role of SLS, two branches of FP, respectively considering the past stress and future reference critical state can be developed. Merits and demerits of these approaches are then discussed, which leads to the definition of the third branch of FP, by considering the influences of both past and future stress states. In addition, some specific cases and potential applications of the third branch can be realised when specific SLS are adopted.

The Association of Folic Acid, Iron Nutrition during Pregnancy and Congenital Heart Disease in Northwestern China: A Matched Case-Control Study.

Background: The purpose of this study was to investigate the relationship between folic acid and iron nutrition during pregnancy and congenital heart disease (CHD) in the offspring. Methods: Conditional logistic regression models and nonlinear mixed-effects models were used to analyze the effects of folic acid and iron nutrition during pregnancy on CHD in offspring. Results: After adjusting for confounders, folic acid or iron supplementation during pregnancy reduced the risk for fetal CHD (OR = 0.60 (0.45, 0.82) or 0.36 (0.27, 0.48)). Similarly, dietary iron intake during pregnancy (≥29 mg/d) was associated with a reduced risk of fetal CHD (OR = 0.64 (0.46, 0.88)). Additionally, compared with women who only supplemented folic acid (OR = 0.59 (0.41, 0.84)) or iron (OR = 0.32 (0.16, 0.60)), women who supplemented both folic acid and iron had lower risk for newborns with CHD (OR = 0.22 (0.15, 0.34)). Similarly, compared with women who only supplemented folic acid (OR = 0.59 (0.41, 0.84)) or higher dietary iron intake (≥29 mg/d) (OR = 0.60 (0.33, 1.09)), women who supplemented both folic acid and higher dietary iron intake (≥29 mg/d) had lower risk for the newborn with CHD (OR = 0.41 (0.28, 0.62)). The combined effects were significant in the multiplication model (OR = 0.35 (0.26, 0.48) or 0.66 (0.50, 0.85)) but not in the additive model. Conclusions: Our study found that folic acid and iron nutrition during pregnancy were associated with a reduced risk of CHD in the offspring and confirmed a statistically significant multiplicative interaction between folic acid and iron nutrition on the reduced risk of CHD in offspring.

Functional analysis of HADH c.99C>G shows that the variant causes the proliferation of pancreatic islets and leu-sensitive hyperinsulinaemia.

A novel missense variant (NM_005327.7: c.99C>G, p.Ile33Met) was discovered in 3-hydroxyacyl-CoA dehydrogenase (HADH), which is involved in congenital hyperinsulinism (CHI). This variant may be damaging or deleterious, as assessed using protein prediction software. This study aimed at the impact of this variant on islets and if it caused the leu-sensitive insulin secretion. The adenoassociated virus containing the HADH missense variant (p.Ile33Met), wild-type (WT) HADH or empty vector (EV) was constructed, and the rats were infected with it. Three weeks after the transfection, 15 rats were dissected to observe the effect of the variant on the islet tissue. Then we treated the remaining rats with leucine or sodium carboxymethyl cellulose (CMC-Na) by gavage and drew blood from the rat tail vein to detect the variations in blood glucose, serum insulin and serum glucagon. Further, we dissected the rats to observe the fluctuation of insulin and glucagon contents in pancreatic islets under the combined action of leucine and p.Ile33Met. Insulin and glucagon were observed in the islet tissue under an inverted fluorescence microscope, serum insulin and glucagon were detected by ELISA, and the blood glucose value was determined using a Roche glucometer. The positive area and average gray value of islet fluorescence pictures were analysed using the software Image J (USA). Rats expressing p.Ile33Met showed significantly higher insulin and glucagon content, as well as the islet area, compared to WT and EV rats. Moreover, after intragastric administration of leucine, the serum insulin content of the variant rats increased but the blood sugar level decreased significantly. Meanwhile, there was an appreciable decrease in the insulin content in rat pancreatic islet tissues. Our results suggest that the variant NM_005327.7: c.99C>G promotes the proliferation of pancreatic islets, enhances the secretion of insulin, and induces leu-sensitive hyperinsulinaemia.