Gestational cholestasis induced intrauterine growth restriction through triggering IRE1α-mediated apoptosis of placental trophoblast cells.

Epidemiological and animal experimental studies suggest an association between gestational cholestasis and intrauterine growth restriction (IUGR). Here, we explored the mechanism through which gestational cholestasis induced IUGR. To establish gestational cholestasis model, pregnant mice were subcutaneously injected with 17α-Ethynylestradiol (E2) on gestational day 13 (GD13)-GD17. Some pregnant mice were intraperitoneally injected with 4µ8C on GD13-GD17. The results found that the apoptosis of trophoblast cells was elevated in placentas of mice with gestational cholestasis and in deoxycholic acid (DCA)-treated human trophoblast cell lines and primary mouse trophoblast cells. Correspondingly, the levels of placental cleaved caspase-3 and Bax were increased, while placental Bcl2 level was decreased in mice with gestational cholestasis and in DCA-treated trophoblast cells. Further analysis found that placental IRE1α pathway was activated in mice with gestational cholestasis and in DCA-treated trophoblast cells. Interestingly, 4µ8C, an IRE1α RNase inhibitor, significantly inhibited caspase-3 activity and apoptosis of trophoblast cells in vivo and in vitro. Importantly, 4µ8C rescued gestational cholestasis-induced placental insufficiency and IUGR. Furthermore, a case-control study demonstrated that placental IRE1α and caspase-3 pathways were activated in cholestasis cases. Our results provide evidence that gestational cholestasis induces placental insufficiency and IUGR may be via triggering IRE1α-mediated apoptosis of placental trophoblast cells.

A study on the impact of the number of family generations on intergenerational support for centenarians: a study in a Chinese 'longevity city'.

BACKGROUND: As a natural source of support for the elderly, the family is an important channel for achieving a sense of security, happiness, and worthiness in old age. In this study, we analysed the characteristics of intergenerational support in families of centenarians and explored the impact of the number of family generations on intergenerational support. METHODS: We conducted a cross-sectional survey between April 2020 and January 2021 among 62 elderly people aged 99+ in Rugao, China, one of six 'longevity cities' in the world. Assisted by the researchers, centenarians completed questionnaires with details pertaining to general demographics, intergenerational support, and other aspects. We used a logistic regression model to analyse the influence of the number of family generations on intergenerational support that the centenarians received with respect to economic, living, and emotional aspects. RESULTS: Centenarians were primarily recipients of care in their families, and received intergenerational support mainly for their declined physical functions and limited self-care ability. The study results revealed that the greater the number of generations comprising the family, the greater was the intergenerational life care and emotional comfort provided for centenarians by the family. CONCLUSIONS: In this study, we found a positive effect of the number of family generations on intergenerational support for centenarians. The government and society should promote the tradition of respecting, caring for, and honouring the elderly while paying close attention to the dynamic changes in the family structure of centenarians in promoting high-quality and sustainable development of the people, economy, and society.

Separation and purification of flavonoid from Taxus remainder extracts free of taxoids using polystyrene and polyamide resin.

An efficient separation process of flavonoid from Taxus wallichiana var. mairei remainder extracts free of taxoids was developed in this study. AB-8 macroporous resin and polyamide resin offered the fine adsorption capacity, and its adsorption rate at 30°C fitted well to the Langmuir and Freundich isotherms. Resin dynamic adsorption and desorption experiments were conducted to optimize the separation process of total flavonoids from T. wallichiana var. mairei remainder extracts free of taxoids. The optimum parameters for adsorption by AB-8 resin were as follows: (1) the concentration of flavonoids in a sample solution of 5.61 mg/mL with a processing volume of 2 bed volume (BV) (60 mL); (2) for desorption, ethanol-water (80:20, v/v), with 6 BV as an eluent at a flow rate of 2 BV/h. After a one-run treatment with AB-8 resin, the content of flavonoids was increased 5.10-fold from 4.05 to 20.65%. The optimum parameters for adsorption by polyamide resin were as follows: processing volume of 2 BV (30 mL); for desorption, ethanol-water (70:30, v/v), with 8 BV as an eluent at a flow rate of 2 BV/h. After one-run treatment with polyamide resin, the content of total flavonoids increased from 20.65 to 65.21%. The method will provide a potential approach for large-scale separation and purification of flavonoid for its wide pharmaceutical use.

Comparison between preoperative hook-wire and liquid material localization for pulmonary nodules: a meta-analysis.

Introduction: Computed tomography (CT)-guided liquid material (LM) and hook-wire (HW) are usually localized for pulmonary nodules (PNs) before video-assisted thoracic surgery (VATS) resection, but the relative advantages of these 2 techniques remain uncertain. Aim: This meta-analysis was conceived to juxtapose the efficacy and safety of HW localization (HWL) and LM localization (LML), both guided by CT, for the preoperative localization of PNs. Material and methods: The PubMed, Web of Science, and Wanfang databases were searched to identify relevant studies published as of March 2023, after which pooled analyses of study outcomes were conducted. Results: A total of 7 studies were included in this meta-analysis from 142 relevant studies. These 7 studies included 551 patients (583 PNs) with CT-guided HWL and 551 patients (612 PNs) with LML. The successful localization rate was significantly higher in the LM group (LMG) than in the HW group (HWG) (p = 0.002). The LMG also exhibited significantly lower pooled total complication and lung haemorrhage rates than the HWG (p = 0.007 and 0.00001, respectively). Pooled localization duration, pneumothorax rates, and VATS procedure duration were comparable in both groups (p = 0.45, 0.15, and 0.74, respectively). Furthermore, the pooled postoperative hospital stay was significantly shorter in the LMG than in the HWG (p = 0.009). Significant heterogeneity was detected in the endpoints of localization duration and pneumothorax rate (I2 = 93% and 66%, respectively). Conclusions: CT-guided LML is safer and more successful than HWL for patients with PNs before VATS resection.

Di-(2-ethylhexyl) phthalate induces testicular endoplasmic reticulum stress and germ cell apoptosis in adolescent mice.

Di-(2-ethylhexyl) phthalate (DEHP) is a male reproductive toxicant. This research is aimed at investigating the effect of pubertal DEHP exposure on testicular endoplasmic reticulum (ER) stress and germ cell apoptosis. Five-week-old male mice were orally administered with DEHP (0, 0.5, 50, or 500 mg/kg/day) for 35 days. Testis weight and sperm count were reduced in mice exposed to 500 mg/kg/day DEHP. The number of seminiferous tubules in stages VII-VIII, mature seminiferous tubules, was reduced and the number of seminiferous tubules in stages IX-XII, immature seminiferous tubules, was elevated in mice treated with 500 mg/kg/day DEHP. Numerous apoptotic germ cells were observed in mouse seminiferous tubules exposed to 50 and 500 mg/kg/day DEHP. Moreover, cleaved caspase-3 was elevated in mouse testes exposed to 500 mg/kg/day DEHP. In addition, Bcl-2 was reduced and Bax/Bcl-2 was elevated in mouse testes exposed to 500 mg/kg/day DEHP. Additional experiment showed that GRP78, an ER molecular chaperone, was downregulated in mouse testes exposed to 500 mg/kg/day DEHP. Testicular p-IRE-1α, p-JNK, and CHOP, three markers of ER stress, were upregulated in mice exposed to 500 mg/kg/day DEHP. These results suggest that pubertal exposure to high doses of DEHP induces germ cell apoptosis partially through initiating ER stress in testes.

Prevalence and risk factors of intrahepatic cholestasis of pregnancy in a Chinese population.

Studies on the risk factors for intrahepatic cholestasis of pregnancy (ICP) in a population-based cohort are lacking. We assess the prevalence and risk factors of ICP in a Chinese population. In this study, a cohort study was conducted that included 12,200 eligible pregnant women. The overall incidence of ICP in this cohort was 6.06%. With increasing maternal age, the incidence of ICP decreased in women younger than 30 years of age but increased in those older than 30. With increasing pre-pregnancy BMI, the incidence of ICP decreased if the pre-pregnancy BMI was less than 23 kg/m2 but increased if it was 23 kg/m2 or higher. Further analysis showed that the risk of ICP increased when maternal age was < 25 years (Adjusted RR 2.01; 95% CI 1.64-2.47) or ≥ 35 years (Adjusted RR 1.34; 95% CI 1.02-1.76). Furthermore, an increased risk of ICP was associated with pre-pregnancy underweight (adjusted RR 1.27; 95% CI 1.04-1.56), inadequate gestational weight gain (GWG) (adjusted RR 1.58; 95% CI 1.28-1.96), lower maternal education (adjusted RR 2.96; 95% CI 2.35-3.74), multiparity (adjusted RR 1.54; 95% CI 1.23-1.93), and twin/multiple pregnancies (adjusted RR 2.12; 95% CI 1.25-3.58). Maternal age (< 25 or ≥ 35 years), underweight, inadequate GWG, lower maternal education, multiparity, and twin/multiple pregnancies were identified as risk factors of ICP.

Continuous association of total bile acid levels with the risk of small for gestational age infants.

The association between maternal serum total bile acid (TBA) levels and small-for-gestational-age (SGA) infants is unclear. We investigated the association between various degrees of serum TBA levels and the risk of SGA infants in a Chinese population. The current study performed a cohort study among 11811 mothers with singleton pregnancy. Subjects were divided into seven categories according to maternal serum TBA levels. Interestingly, birth sizes were reduced, whereas the rate of SGA infants was increased across increasing categories of serum TBA. Compared to category 1, adjusted ORs (95%CI) for SGA infants were 0.99 (0.82-1.21) in category 2, 1.22 (0.97-1.53) in category 3, 1.99 (1.53-2.58) in category 4, 2.91 (2.16-3.93) in category 5, 4.29 (3.33-5.54) in category 6, and 9.01 (5.99-13.53) in category 7, respectively. Furthermore, adjusted ORs (95%CI) for SGA infants for each 1-SD increase in serum TBA levels were 1.36 (1.29-1.43) among all subjects, 2.40 (1.82-3.45) among subjects without cholestasis, and 1.13 (1.06-1.22) among subjects with cholestasis, respectively. These results suggest that gestational cholestasis increases the risk of SGA infants. Additionally, our results indicate strong, continuous associations of serum TBA levels below those diagnostic of cholestasis with a decreased birth sizes and an increased risk of SGA infants.

Pre-pregnancy underweight and obesity are positively associated with small-for-gestational-age infants in a Chinese population.

The association between suboptimal pre-pregnancy body mass index (BMI) and small-for-gestational-age (SGA) infants is not well defined. We investigated the association between pre-pregnancy BMI and the risk of SGA infants in a Chinese population. We performed a cohort study among 12029 mothers with a pregnancy. This cohort consisted of pregnant women that were: normal-weight (62.02%), underweight (17.09%), overweight (17.77%) and obese (3.12%). Birth sizes were reduced in the underweight and obese groups compared with the normal-weight group. Linear regression analysis indicated that birth size was positively associated with BMI in both the underweight and normal-weight groups. Further analysis showed that 12.74% of neonates were SGA infants in the underweight group, higher than 7.43% of neonates reported in the normal-weight group (adjusted RR = 1.92; 95% CI: 1.61, 2.30). Unexpectedly, 17.60% of neonates were SGA infants in the obese group, much higher than the normal-weight group (adjusted RR = 2.17; 95% CI: 1.57, 3.00). Additionally, 18.40% of neonates were large-for-gestational-age (LGA) infants in the obese group, higher than 7.26% of neonates reported in the normal-weight group (adjusted RR = 3.00; 95% CI: 2.21, 4.06). These results suggest that pre-pregnancy underweight increases the risk of SGA infants, whereas obesity increases the risks of not only LGA infants, but also SGA infants.

Obeticholic Acid Protects against Gestational Cholestasis-Induced Fetal Intrauterine Growth Restriction in Mice.

Gestational cholestasis is a common disease and is associated with adverse pregnancy outcomes. However, there are still no effective treatments. We investigated the effects of obeticholic acid (OCA) on fetal intrauterine growth restriction (IUGR) during 17α-ethynylestradiol- (E2-) induced gestational cholestasis in mice. All pregnant mice except controls were subcutaneously injected with E2 (0.625 mg/kg) daily from gestational day (GD) 13 to GD17. Some pregnant mice were orally administered with OCA (5 mg/kg) daily from GD12 to GD17. As expected, OCA activated placental, maternal, and fetal hepatic FXR signaling. Additionally, exposure with E2 during late pregnancy induced cholestasis, whereas OCA alleviated E2-induced cholestasis. Gestational cholestasis caused reduction of fetal weight and crown-rump length and elevated the incidence of IUGR. OCA decreased the incidence of IUGR during cholestasis. Interestingly, OCA attenuated reduction of blood sinusoid area in placental labyrinth layer and inhibited downregulation of placental sodium-coupled neutral amino acid transporter- (SNAT-) 2 during cholestasis. Additional experiment found that OCA attenuated glutathione depletion and lipid peroxidation in placenta and fetal liver and placental protein nitration during cholestasis. Moreover, OCA inhibited the upregulation of placental NADPH oxidase-4 and antioxidant genes during cholestasis. OCA activated antioxidant Nrf2 signaling during cholestasis. Overall, we demonstrated that OCA treatment protected against gestational cholestasis-induced placental dysfunction and IUGR through suppressing placental oxidative stress and maintaining bile acid homeostasis.