Rapid Progress in Intelligent Radiotherapy and Future Implementation.

Radiotherapy is one of the major approaches to cancer treatment. Artificial intelligence in radiotherapy (shortly, Intelligent radiotherapy) mainly involves big data, deep learning, extended reality, digital twin, radiomics, Internet plus and Internet of Things (IoT), which establish an automatic and intelligent network platform consisting of radiotherapy preparation, target volume delineation, treatment planning, radiation delivery, quality assurance (QA) and quality control (QC), prognosis judgment and post-treatment follow-up. Intelligent radiotherapy is an interdisciplinary frontier discipline in infancy. The review aims to summary the important implements of intelligent radiotherapy in various areas and put forward the future of unmanned radiotherapy center.

A randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in women at high risk in China.

BACKGROUND: Low-dose aspirin has been the most widely studied preventive drug for preeclampsia. However, guidelines differ considerably from country to country regarding the prophylactic use of aspirin for preeclampsia. There is limited evidence from large trials to determine the effect of 100 mg of aspirin for preeclampsia screening in women with high-risk pregnancies, based on maternal risk factors, and to guide the use of low-dose aspirin in preeclampsia prevention in China. OBJECTIVE: The Low-Dose Aspirin in the Prevention of Preeclampsia in China study was designed to evaluate the effect of 100 mg of aspirin in preventing preeclampsia among high-risk pregnant women screened with maternal risk factors in China, where preeclampsia is highly prevalent, and the status of low-dose aspirin supply is commonly suboptimal. STUDY DESIGN: We conducted a multicenter randomized controlled trial at 13 tertiary hospitals from 11 provinces in China between 2016 and 2019. We assumed that the relative reduction in the incidence of preeclampsia was at least 20%, from 20% in the control group to 16% in the aspirin group. Therefore, the targeted recruitment number was 1000 participants. Women were randomly assigned to the aspirin or control group in a 1:1 allocation ratio. Statistical analyses were performed according to an intention-to-treat basis. The primary outcome was the incidence of preeclampsia, diagnosed along with a systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg after 20 weeks of gestation, with a previously normal blood pressure (systolic blood pressure of <140 mm Hg and diastolic blood pressure of <90 mm Hg), and complicated by proteinuria. The secondary outcomes included maternal and neonatal outcomes. Logistic regression analysis was used to determine the significance of difference of preeclampsia incidence between the groups for both the primary and secondary outcomes. Interaction analysis was also performed. RESULTS: A total of 1000 eligible women were recruited between December 2016 and March 2019, of which the final 898 patients were analyzed (464 participants in the aspirin group, 434 participants in the control group) on an intention-to-treat basis. No significant difference was found in preeclampsia incidence between the aspirin group (16.8% [78/464]) and the control group (17.1% [74/434]; relative risk, 0.986; 95% confidence interval, 0.738-1.317; P=.924). Likewise, adverse maternal and neonatal outcomes did not differ significantly between the 2 groups. Meanwhile, the incidence of postpartum hemorrhage between the 2 groups was similar (6.5% [30/464] in the aspirin group and 5.3% [23/434] in the control group; relative risk, 1.220; 95% confidence interval, 0.720-2.066; P=.459). We did not find any significant differences in preeclampsia incidence between the 2 groups in the subgroup analysis of the different risk factors. CONCLUSION: A dosage of 100 mg of aspirin per day, initiated from 12 to 20 gestational weeks until 34 weeks of gestation, did not reduce the incidence of preeclampsia in pregnant women with high-risk factors in China.

Associations of dietary patterns and pre-eclampsia: a matched case-control study.

Little is known about the effects of dietary patterns on prevalent pre-eclampsia in Chinese population. This study aimed to investigate the associations between dietary patterns and the odds of pre-eclampsia among Chinese pregnant women. A 1:1 age- and gestational week-matched case-control study was conducted between March 2016 and February 2019. A total of 440 pairs of pre-eclampsia cases and healthy controls were included. Dietary intakes were assessed by a seventy-nine-item FFQ and subsequently grouped into twenty-eight distinct groups. Factor analysis using the principal component method was adopted to derive the dietary patterns. Conditional logistic regression was used to analyse the associations of dietary patterns with prevalent pre-eclampsia. We identified four distinct dietary patterns: high fruit-vegetable, high protein, high fat-grain and high salt-sugar. We found that high fruit-vegetable dietary pattern (quartile (Q)4 v. Q1, OR 0·71, 95 % CI 0·55, 0·92, Ptrend = 0·013) and high protein dietary pattern (Q4 v. Q1, OR 0·72, 95 % CI 0·54, 0·95, Ptrend = 0·011) were associated with a decreased odds of pre-eclampsia in Chinese pregnant women. Whereas high fat-grain dietary pattern showed a U-shaped association with pre-eclampsia, the lowest OR was observed in the third quartile (Q3 v. Q1, OR 0·75, 95 % CI 0·57, 0·98, Ptrend = 0·111). No significant association was observed for high salt-sugar dietary pattern. In conclusion, pregnancy dietary pattern characterised by high fruit-vegetable or high protein was found to be associated with a reduced odds of pre-eclampsia in Chinese pregnant women.

Dietary inflammatory index, inflammation biomarkers and preeclampsia risk: a hospital-based case-control study.

This study evaluated the association between inflammatory diets as measured by the Dietary Inflammatory index (DII), inflammation biomarkers and the development of preeclampsia among the Chinese population. We followed the reporting guidelines of the Strengthening the Reporting of Observational Studies in Epidemiology statement for observational studies. A total of 466 preeclampsia cases aged over 18 years were recruited between March 2016 and June 2019, and 466 healthy controls were 1:1 ratio matched by age (±3 years), week of gestation (±1 week) and gestational diabetes mellitus. The energy-adjusted DII (E-DII) was computed based on dietary intake assessed using a seventy-nine item semiquantitative FFQ. Inflammatory biomarkers were analysed by ELISA kits. The mean E-DII scores were -0·65 ± 1·58 for cases and -1·19 ± 1·47 for controls (P value < 0·001). E-DII scores positively correlated with interferon-γ (r s = 0·194, P value = 0·001) and IL-4 (r s = 0·135, P value = 0·021). After multivariable adjustment, E-DII scores were positively related to preeclampsia risk (Ptrend < 0·001). The highest tertile of E-DII was 2·18 times the lowest tertiles (95 % CI = 1·52, 3·13). The odds of preeclampsia increased by 30 % (95 % CI = 18 %, 43 %, P value < 0·001) for each E-DII score increase. The preeclampsia risk was positively associated with IL-2 (OR = 1·07, 95 % CI = 1·03, 1·11), IL-4 (OR = 1·26, 95 % CI = 1·03, 1·54) and transforming growth factor beta (TGF-ß) (OR = 1·17, 95 % CI = 1·06, 1·29). Therefore, proinflammatory diets, corresponding to higher IL-2, IL-4 and TGF-ß levels, were associated with increased preeclampsia risk.

Dietary and serum vitamin D and preeclampsia risk in Chinese pregnant women: a matched case-control study.

The effect of vitamin D (VD) on the risk of preeclampsia (PE) is uncertain. Few of previous studies focused on the relationship between dietary VD intake and PE risk. Therefore, we conducted this 1:1 matched case-control study to explore the association of dietary VD intake and serum VD concentrations with PE risk in Chinese pregnant women. A total of 440 pairs of participants were recruited during March 2016 to June 2019. Dietary information was obtained using a seventy-eight-item semi-quantitative FFQ. Serum concentrations of 25(OH)D2 and 25(OH)D3 were measured by liquid chromatography-tandem MS. Multivariate conditional logistic regression was used to estimate OR and 95 % CI. Restricted cubic splines (RCS) were plotted to evaluate the dose-response relationship of dietary VD intake and serum VD concentrations with PE risk. Compared with the lowest quartile, the OR of the highest quartile were 0·45 (95 % CI 0·29, 0·71, Ptrend = 0·001) for VD dietary intake and 0·26 (95 % CI 0·11, 0·60, Ptrend = 0·003) for serum levels after adjusting for confounders. In addition, the RCS analysis suggested a reverse J-shaped relationship between dietary VD intake and PE risk (P-nonlinearity = 0·02). A similar association was also found between serum concentrations of total 25(OH)D and PE risk (P-nonlinearity = 0·02). In conclusion, this study provides evidence that higher dietary intake and serum levels of VD are associated with the lower risk of PE in Chinese pregnant women.

Dietary carotenoid intake and risk of developing preeclampsia: a hospital-based case-control study.

BACKGROUND: The effect of carotenoids on the risk of preeclampsia (PE) is uncertain. We aimed to examine the associations between the intake of dietary carotenoids and related compounds by pregnant women in China, and the risk of their developing PE. METHODS: Four hundred and forty PE cases and 440 age- (± 3 years), gestational age- (± 1 weeks) and gestational diabetes mellitus status- (yes/no) matched healthy controls were recruited from March 2016 to June 2019. Dietary intake of carotenoids was assessed using a 79-item validated food-frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. RESULTS: After adjusting for potential confounders, we found that the intake of total carotenoids, ß-carotene, ß-cryptoxanthin, lycopene, and lutein and zeaxanthin (lut-zea) were negatively associated with the odds of developing PE. Compared with the lowest quartile intake, the multivariate-adjusted OR (95% CI) of the highest quartile intake was 0.29 (0.16-0.54, Ptrend <  0.001) for total carotenoids, 0.31 (0.16-0.58, Ptrend <  0.001) for ß-carotene, 0.50 (0.27-0.90, Ptrend = 0.007) for ß-cryptoxanthin, 0.55 (0.30-0.99, Ptrend = 0.04) for lycopene and 0.32 (0.17-0.61, Ptrend = 0.001) for lut-zea. However, no significant associations were observed between the risk of developing PE and α-carotene intake (OR = 0.75, 95% CI: 0.41-1.36, Ptrend = 0.28). Moreover, similar negative associations were found for every one-standard-deviation increase in the intake of total carotenoids, ß-carotene, ß-cryptoxanthin, lycopene and lut-zea. CONCLUSION: These results indicate that a high intake of total carotenoids, ß-carotene, ß-cryptoxanthin, lycopene and lut-zea may be associated with a low risk of developing PE.

Maternal age at first cesarean delivery related to adverse pregnancy outcomes in a second cesarean delivery: a multicenter, historical, cross-sectional cohort study.

BACKGROUND: To determine the effects of maternal age at first cesarean on maternal complications and adverse outcomes of pregnancy with the second cesarean. METHODS: This was a multicenter, historical, cross-sectional cohort study involving singleton pregnancies ≥28 gestational weeks, with a history of 1 cesarean delivery, and who underwent a second cesarean between January and December 2017 at 11 public tertiary hospitals in 7 provinces of China. We analyzed the effects of maternal age at first cesarean on adverse outcomes of pregnancy in the second cesarean using multivariate logistic regression analysis. RESULTS: The study consisted of 10,206 singleton pregnancies. Women were at first cesarean between 18 and 24, 25-29, 30-34, and ≥ 35 years of age; and numbered 2711, 5524, 1751, and 220 cases, respectively. Maternal age between 18 and 24 years at first cesarean increased the risk of placenta accreta spectrum (aOR, 1.499; 95% CI, 1.12-2.01), placenta previa (aOR, 1.349; 95% CI, 1.07-1.70), intrahepatic cholestasis of pregnancy (aOR, 1.947; 95% CI, 1.24-3.07), postpartum hemorrhage (aOR, 1.505; 95% CI, 1.05-2.16), and blood transfusion (aOR, 1.517; 95% CI, 1.21-1.91) in the second cesarean compared with the reference group (aged 25-29 years). In addition, maternal age ≥ 35 years at first cesarean was a risk factor for premature rupture of membranes (aOR, 1.556; 95% CI, 1.08-2.24), placental abruption (aOR, 6.464, 95% CI, 1.33-31.51), uterine rupture (aOR, 7.952; 95% CI, 1.43-44.10), puerperal infection (aOR, 6.864; 95% CI, 1.95-24.22), neonatal mild asphyxia (aOR, 4.339; 95% CI, 1.53-12.32), severe asphyxia (aOR, 18.439; 95% CI, 1.54-220.95), and admission to a neonatal intensive care unit (aOR, 2.825; 95% CI, 1.54-5.17) compared with the reference group (aged 25-29 years). CONCLUSIONS: Maternal age between 18 and 24 years or advanced maternal age at first cesarean was an independent risk factor for adverse maternal outcomes with the second cesarean. Advanced maternal age at the first cesarean specifically increased adverse neonatal outcomes with the second. Therefore, decisions as to whether to perform a first cesarean at a young or advanced maternal age must be critically evaluated.

Development and Validation of Predictive Models for Vaginal Birth After Cesarean Delivery in China.

BACKGROUND The rate of delivery by cesarean section is rising in China, where vaginal birth after cesarean (VBAC) is in its early stages. There are no validated screening tools to predict VBAC success in China. The objective of this study was to identify the variables predicting the likelihood of successful VBAC to create a predictive model. MATERIAL AND METHODS This multicenter, retrospective study included 1013 women at ≥28 gestational weeks with a vertex singleton gestation and 1 prior low-transverse cesarean from January 2017 to December 2017 in 11 public tertiary hospitals within 7 provinces of China. Two multivariable logistic regression models were developed: (1) at a first-trimester visit and (2) at the pre-labor admission to hospital. The models were evaluated with the area under the receiver operating characteristic curve (AUC) and internally validated using k-fold cross-validation. The pre-labor model was calibrated and a graphic nomogram and clinical impact curve were created. RESULTS A total of 87.3% (884/1013) of women had successful VBAC, and 12.7% (129/1013) underwent unplanned cesarean delivery after a failed trial of labor. The AUC of the first-trimester model was 0.661 (95% confidence interval [CI]: 0.61-0.712), which increased to 0.758 (95% CI: 0.715-0.801) in the pre-labor model. The pre-labor model showed good internal validity, with AUC 0.743 (95% CI: 0.694-0.785), and was well calibrated. CONCLUSIONS VBAC provides women the chance to experience a vaginal delivery. Using a pre-labor model to predict successful VBAC is feasible and may help choose mode of birth and contribute to a reduction in cesarean delivery rate.

Long noncoding RNA SOX21-AS1 promotes cervical cancer progression by competitively sponging miR-7/VDAC1.

Growing evidence has shown that long noncoding RNAs (lncRNAs) play crucial roles in cervical cancer. Dy000sregulation of lncRNA SOX21 antisense RNA 1 (SOX21-AS1) has been reported in several tumors. However, its expression pattern and potential biological function in cervical cancer (CC) have not been investigated. In this study, we first reported that SOX21-AS1 expression was significantly upregulated in both CC tissues and cell lines. High expression of SOX21-AS1 was found to be significantly correlated with Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis and depth of cervical invasion. Further clinical assay confirmed that high SOX21-AS1 expression was associated with shorter overall survival and could be used as a potential prognostic biomarker for CC patients. Functional investigation showed that knockdown of SOX21-AS1 suppressed CC cells proliferation, migration, and invasion, as well as epithelial to mesenchymal transition progress. Furthermore, our data showed that microRNA-7 (miR-7) interacted with SOX21-AS1 by directly targeting the miRNA-binding site in the SOX21-AS1 sequence, and quantitative real-time polymerase chain reaction results showed overexpression of SOX21-AS1 decreased the levels of miR-7 in CC cells. Moreover, we confirmed that miR-7 directly targeted the 3'-untranslated region of voltage dependent anion channel 1 (VDAC1). Final in vitro assay suggested that in CC cells with SOX21-AS1, VDAC1 overexpression resulted in an increase of cell proliferation, migration, and invasion. Overall, our findings illuminate how SOX21-AS1 formed a regulatory network to confer an oncogenic function in CC and SOX21-AS1 could be regarded as an efficient therapeutic target and potential biomarker for CC patients.

Acute fatty liver of pregnancy in a Chinese Tertiary Care Center: a retrospective study.

PURPOSE: To describe some prenatal clinical features and laboratory findings of AFLP and provide the clinicians with potential predictors in postpartum recovery time. METHODS: Forty-four cases of AFLP previously treated in the First Affiliated Hospital of Zhengzhou University were retrospectively reviewed. RESULTS: The maternal and fetal mortalities after treatment were both 18.2%. The main symptoms of AFLP were nausea and vomiting (63.6%), jaundice (61.4%). Moreover, the most common maternal complication was acute renal dysfunction (79.5%), followed by DIC (47.7%) and MODS (38.6%). The level of platelets, total protein and total bilirubin were found to be correlated with postpartum recovery time (Pearson correlation coefficient 0.434, P = 0.008; 0.466, P = 0.005; 0.484, P = 0.003). CONCLUSIONS: AFLP is a rare, but lethal complication in the third trimester. Termination of pregnancy should be applied once AFLP was highly suspected. Prenatal platelets, total protein and total bilirubin may be potential predictors of postpartum recovery.

[Association between nutrition factors in the third trimeter and preeclampsia:a case-control study].

OBJECTIVE: To investigate the relationship between dietary intake during the third trimester and preeclampsia. METHODS: A case-control study with 1∶1 matching was performed. A total of 131 patients with preeclampsia hospitalized in the First Affiliated Hospital of Zhengzhou University from March 2016 to December 2016 were selected as the case group. According to age ±3 years and gestational age ±2 weeks, 131 pregnant women with normal blood pressure and no proteinuria in the hospital were randomly selected as the control group. The questionnaires of food frequency and gestational health risk factors in the past three months were conducted and the average daily intakes of various nutrients were calculated. Conditional Logistic regression was applied to analyze the data. RESULTS: Multivariate conditional Logistic regression showed that pre-pregnancy body mass index(OR=1. 18, 95%CI 1. 08-2. 82) and gestational weight gain(OR=1. 51, 95%CI 1. 15-1. 97) were higher, while the intakes of red and/or yellow fruits(OR=0. 76, 95%CI 0. 60-0. 98), and dietary vitamin C(OR=0. 57, 95%CI 0. 33-0. 99) and folic acid(OR=0. 36, 95%CI 0. 18-0. 72) were lower in case group than that in control group(P<0. 05). CONCLUSION: Higher pre-pregnancy body mass index and over gestational weight gain are the risk factors for pre-eclampsia. Appropriate increase of red and/or yellow fruit intake during pregnancy may be beneficial to prevent pre-eclampsia. Vitamin C and folic acid intake might be protective factors for pre-eclampsia. .

Comparison of temporary abdominal aortic occlusion with internal iliac artery occlusion for patients with placenta accreta - a non-randomised prospective study.

BACKGROUND: To compare the efficacy of temporary abdominal aortic occlusion with internal iliac artery occlusion for the management of placenta accreta. PATIENTS AND METHODS: 105 patients with placenta accreta were selected for treatment with temporary abdominal aortic occlusion (n = 57, group A) or bilateral iliac artery occlusion (n = 48, group B). Temporary abdominal aortic and internal iliac artery balloon occlusions were performed during caesarean sections. Data regarding the clinical success, blood loss, blood transfusion, balloon insertion time, fluoroscopy time, balloon occlusion time, foetal radiation dose, and complications were collected. RESULTS: Temporary abdominal aortic occlusion and bilateral internal iliac artery occlusion were technically successful in all patients. The amount of blood loss (P < 0.001), amount of blood transfusion (P < 0.001), balloon insertion time (P < 0.001), foetal radiation dose (P < 0.001) and fluoroscopy time (P < 0.01) in group A were significantly lower than those of patients in group B. No marked differences were found between these 2 groups with respect to age, mean postoperative hospital stay, balloon occlusion time, and Apgar score (p > 0.05). CONCLUSIONS: Temporary abdominal aortic balloon occlusion resulted in better clinical outcomes with less blood loss, blood transfusion, balloon insertion time, fluoroscopy time and foetal radiation dose than those in bilateral internal iliac balloon occlusion.
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Efficacy and safety of cord blood-derived cytokine-induced killer cells in treatment of patients with malignancies.

BACKGROUND AIMS: Adoptive immunotherapy with the use of cytokine-induced killer (CIK) cells represents an effective therapeutic option for treating malignancies. The characteristics and function of cord blood-derived CIK (CB-CIK) cells have been evaluated both in vitro and in vivo. In this study, we assessed the efficacy and safety of administering CB-CIK cells to patients with cancer. METHODS: In this retrospective clinical trial, 15 patients with cancer received CB-CIK therapy with different cycles from April 2012 to August 2014. CB-CIK cells demonstrated a high percentage of main functional fraction CD3(+)CD56(+) and efficient anti-tumor activity in vitro. RESULTS: After the infusion of CB-CIK cells, the subsets of CD3(+)CD4(+) T lymphocytes and CD3(-)CD56(+) T cells in the peripheral blood were significantly increased compared with those before the therapy. Of 15 patients, one patient with hepatocellular cancer and one patient with esophageal cancer achieved complete responses, two patients with ovarian cancer obtained partial remissions, 10 patients had stable disease and one patient with hepatocellular cancer had progressive disease. Acute toxicities including fever, slight fever, dizziness and other neurologic toxicities were few and occurred in patients after infusion of CB-CIK cells. CONCLUSIONS: These results demonstrated the feasibility and safety of treating malignancies with CB-CIK cells. The study provides a potential therapeutic approach for the patients with poor health or older patients who cannot tolerate repeated collection of blood.

Phenotypic characterization and anti-tumor effects of cytokine-induced killer cells derived from cord blood.

BACKGROUND AIMS: Cytokine-induced killer (CIK) cell therapy represents a feasible immunotherapeutic option for treating malignancies. However, the number of anti-tumor lymphocytes cannot be easily obtained from the cancer patients with poor immunity status, and older patients cannot tolerate repeated collection of blood. Cord blood-derived CIK (CB-CIK) cells have shown efficacy in treating the patients with cancer in several clinical trials. This study was conducted to evaluate the biological characteristics and anti-tumor function of CB-CIK cells. METHODS: The immunogenicity, chemokine receptors and proliferation of CB-CIK cells were analyzed by flow cytometry. The CIK cells on day 13 were treated with cisplatin and the anti-apoptosis capacity was analyzed. The function of CB-CIK cells against the human cancer was evaluated both in vitro and in vivo. RESULTS: Compared with peripheral blood-derived CIK (PB-CIK) cells, CB-CIK cells demonstrated lower immunogenicity and increased proliferation rates. CB-CIK cells also had a higher percentage of main functional fraction CD3(+)CD56(+). The anti-apoptosis ability of CB-CIK cells after treatment with cisplatin was higher than that of PB-CIK cells. Furthermore, CB-CIK cells were effective for secreting interleukin-2 and interferon-γ and a higher percentage of chemokine receptors CCR6 and CCR7. In addition, tumor growth was greatly inhibited by CB-CIK treatment in a nude mouse xenograft model. CONCLUSIONS: CB-CIK cells exhibit more efficient anti-tumor activity in in vitro analysis and in the preclinical model and may serve as a potential therapeutic approach for the treatment of cancer.

[Effect of S100 calcium binding protein A12 on the pathogenesis of preeclampsia].

OBJECTIVE: To investigate the role of S100 calcium binding protein A12 (S100A12) in the pathogenesis of preeclampsia. METHODS: Sixty patients with preeclampsia were recruited from March 2013 to December 2013 in the First Affiliated Hospital of Zhengzhou University. Among them, thirty cases were defined as the mild preeclampsia group and thirty cases were defined as the severe preeclampsia group. The other thirty healthy pregnant women were recruited in the healthy pregnant women group. The levels of S100A12 protein in maternal peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry of streptavidin peroxidase biotin (SP) method was used to measure the protein expression of S100A12. The trophoblast cells were cultured in vitro with plasma from the three groups, and a blank control group was set up as well. Transwell was used to detect the cytotrophoblast invasion ability. Western blot was used to measure the protein expression level of receptor for advanced glycation end products (RAGE). RESULTS: (1) The levels of S100A12 in maternal peripheral blood of patients with preeclampisa [mild group: (30.8±2.7) µg/L, severe group: (49.3±4.1) µg/L] were significantly higher than that of the control group [(15.8±1.4) µg/L]. In addition, compared with the mild preeclampsia group, the level of S100A12 in the severe preeclampsia group was significantly higher (P < 0.05). (2) Positive immunostaining of S100A12 was observed in the cytoplasm of cytotrophoblast, decidual cells and the placentas from the three groups. The positive rate in the mild preeclampisa group was 77% (23/30); in the severe preeclampsia group it was 93% (28/30); and in the healthy pregnant women group it was 23% (7/30). The positive rates of placenta in the mild and severe preeclampsia groups were significantly higher than that in the healthy pregnant women group (P < 0.05). In addition, compared with the mild preeclampsia group, the positive rate of immunostaining of S100A12 in the severe group was significantly higher (P < 0.05). (3) Cytotrophoblast invasion ability and the expression of RAGE in the mild preeclampsia group were 29.1±3.2 and 0.479±0.038, respectively; in the severe preeclampsia group they were 16.8±2.5 and 0.652±0.059; in the healthy pregnant women group they were 38.6±24.3 and 0.327±0.024; and in the blank control group they were 42.6±5.6 and 0.194±0.011. Cytotrophoblast invasion ability and the expression of RAGE protein in the mild and severe preeclampsia groups were significantly higher than those in the healthy pregnant women group and the control group(P < 0.05). CONCLUSIONS: The expression of S100A12 increased in materal peripheral blood and placenta, and the receptor protein of S100A12 RAGE also had high expression. It suggested that the S100A12 may have some effect on the pathogenesis of preeclampsia.

Fetal endothelial colony-forming cells: Possible targets for prevention of the fetal origins of adult diseases.

Endothelial colony-forming cells (ECFCs), a subset of circulating and resident endothelial progenitor cells, are capable of self-renewal and de novo vessel formation, and are known key regulators of vascular integrity and homeostasis. Numerous studies have found that exposure to hostile environment during the fetal development exerts a profound influence on the level and function of ECFCs, which may be the underlying factor linking endothelial dysfunction to cardiovascular disease of the offspring in later life. Herein, we focus on the latest findings regarding the effects of pregnancy-related disorders on the frequency and function of fetal ECFCs. Subsequently, we discuss about placental ECFCs and put forward some details that should be paid attention to in the process of ECFC isolation and culture. Overall, the information presented in this review highlight the potential of ECFCs as a future biomarker or even therapeutic targets for the pregnancy-related adverse maternal and fetal outcomes.

Targeting ZDHHC21/FASN axis for the treatment of diffuse large B-cell lymphoma.

S-palmitoylation is essential for cancer development via regulating protein stability, function and subcellular location, yet the roles S-palmitoylation plays in diffuse large B-cell lymphoma (DLBCL) progression remain enigmatic. In this study, we uncovered a novel function of the palmitoyltransferase ZDHHC21 as a tumor suppressor in DLBCL and identified ZDHHC21 as a key regulator of fatty acid synthetase (FASN) S-palmitoylation for the first time. Specifically, ZDHHC21 was downregulated in DLBCL, and its expression level was associated with the clinical prognosis of patients with DLBCL. In vitro and in vivo experiments suggested that ZDHHC21 suppressed DLBCL cell proliferation. Mechanistically, ZDHHC21 interacted with FASN and mediated its palmitoylation at Cys1317, resulting in a decrease in FASN protein stability and fatty acid synthesis, consequently leading to the inhibition of DLBCL cell growth. Of note, an FDA-approved small-molecule compound lanatoside C interacted with ZDHHC21, increased ZDHHC21 protein stability and decreased FASN expression, which contributed to the suppression of DLBCL growth in vitro and in vivo. Our results demonstrate that ZDHHC21 strongly represses DLBCL cell proliferation by mediating FASN palmitoylation, and suggest that targeting ZDHHC21/FASN axis is a potential therapeutic strategy against DLBCL.

DNMT1 mediates proliferation, migration and invasion of extravillous trophoblasts by regulating the methylation level of APLNR.

INTRODUCTION: Proliferation, migration and invasion of extravillous trophoblasts (EVTs) play an important role in the progression of preeclampsia (PE). The purpose of this study was to investigate the molecular mechanism by which DNA methylase regulates the transcription level of APLNR and affects the phenotypic function of EVTs. MATERIALS AND METHODS: PE mice model and H/R model in HTR8/Svneo cells were constructed. Clinical samples of normal pregnant women and PE patients were collected. Expression and methylation level of APLNR in vivo and in vitro were detected. ChIP-qPCR was used to detect the binding of DNA methyltransferase at the APLNR promoter. The expression of DNA methyltransferase 1 (DNMT1), NO and eNOS in vitro were detected. EVTs proliferation, migration and invasion in vitro were detected. RESULTS: In placental tissues or HTR8/Svneo cells of the PE model group, the expression of APLNR was reduced and APLNR methylation level was up-regulated. There was no significant difference in the APLNR expression in placental tissues between normal pregnant women and PE patients. H/R conditions only promote the binding of DNMT1 at the APLNR promoter. DNMT1 interference decreased the enrichment degree of DNMT1 in APLNR promoter region and up-regulated the mRNA and protein levels of APLNR in vivo and in vitro. The activation of APLNR by Elabela (ELA) can promote eNOS transcription, thereby promoting cell proliferation and NO level, while eNOS inhibitor can reverse this effect. DNMT1 down-regulation inhibted APLNR methylation level, promoted eNOS transcription, and promoted EVTs proliferation, migration and invasion, which could be revised by the interference of APLNR. DISCUSSION: DNMT1 promotes eNOS transcription by inhibting APLNR methylation level, and promotes EVTs proliferation, migration and invasion, thus providing a new and broad application prospect for PE treatment.

Subsequent pregnancy outcomes and risk factors following conservative treatment for placenta accreta spectrum: a retrospective cohort study.

BACKGROUND: Placenta accreta spectrum can lead to uncontrollable massive hemorrhage in the perinatal period. Currently, the first-line treatment for placenta accreta spectrum recommended worldwide is hysterectomy. However, adverse outcomes after hysterectomy, including surgical complications, such as difficulty in performing the procedure, and sequelae, such as infertility and psychological issues, cannot be ignored. Several surgical approaches for conservative treatment have been proposed. There are few reports on the effectiveness, safety, and long-term complications of conservative treatments, especially subsequent pregnancy outcomes. OBJECTIVE: This study aimed to investigate the clinical outcomes and identify risk factors of subsequent pregnancies among patients with placenta accreta spectrum who had undergone conservative surgery. STUDY DESIGN: This was a retrospective cohort study of subsequent pregnancy cases after cesarean delivery with conservative treatment for placenta accreta spectrum from 2011 to 2019 at The First Affiliated Hospital of Zhengzhou University to identify clinical outcomes of subsequent pregnancies and the risk factors of adverse pregnancy outcomes. RESULTS: A total of 883 patients undergoing conservative surgery were included in this study, among which 604 (68.4%) were successfully followed up. There were 75 successful pregnancies in 72 patients, including 22 full-term or near-term deliveries, 1 induced labor in the second trimester of pregnancy, 6 cesarean scar pregnancies (8.0%), 2 ectopic pregnancies, and 44 first-trimester pregnancies (3 miscarriages and 41 elective abortions and 12 medical abortions and 32 vacuum aspirations). All newborns survived in the 22 full-term or near-term deliveries. Moreover, 5 placenta accreta spectrum cases (22.7%) and 6 placenta previa cases were observed. Postpartum hemorrhage was observed in 2 cases, with an incidence rate of 9.1%. All parameters, including age at subsequent pregnancy, gravidity, number of cesarean deliveries, type of previous placenta accreta spectrum, gestational week of pregnancy termination, interpregnancy interval, and the use of vascular occlusion techniques, were not found to be associated with recurrent placenta accreta spectrum and cesarean scar pregnancy. CONCLUSION: Our findings show that treatment for placenta accreta spectrum does not automatically preclude a subsequent pregnancy. However, patients should be fully informed about the risk of recurrent placenta accreta spectrum, scar pregnancy, and postpartum hemorrhage.

Advances in single-cell RNA sequencing and its applications in cancer research.

Cancers are a group of heterogeneous diseases characterized by the acquisition of functional capabilities during the transition from a normal to a neoplastic state. Powerful experimental and computational tools can be applied to elucidate the mechanisms of occurrence, progression, metastasis, and drug resistance; however, challenges remain. Bulk RNA sequencing techniques only reflect the average gene expression in a sample, making it difficult to understand tumor heterogeneity and the tumor microenvironment. The emergence and development of single-cell RNA sequencing (scRNA-seq) technologies have provided opportunities to understand subtle changes in tumor biology by identifying distinct cell subpopulations, dissecting the tumor microenvironment, and characterizing cellular genomic mutations. Recently, scRNA-seq technology has been increasingly used in cancer studies to explore tumor heterogeneity and the tumor microenvironment, which has increased the understanding of tumorigenesis and evolution. This review summarizes the basic processes and development of scRNA-seq technologies and their increasing applications in cancer research and clinical practice.