Necroptosis in recurrent implantation failure: A bioinformatics analysis of key genes and therapeutic targets.

Recurrent implantation failure (RIF), a major issue in assisted reproductive technology (ART), may be influenced by necroptosis, a form of cell death linked to several diseases. This study was aimed at investigating the involvement of necroptosis in RIF. Using RNA-sequencing data from the Gene Expression Omnibus database, we identified differentially expressed necroptosis-related genes (DENRGs) in RIF patients compared with those in controls. Functional enrichment, protein-protein interaction (PPI) networks, and transcription factor (TF) regulatory networks were analyzed to identify key genes. Immune cell infiltration was analyzed using the single-sample gene set enrichment analysis (ssGSEA) algorithm. Finally, potential therapeutic drugs targeting key genes were explored using a Drug Gene Interaction Database. In total, 20 DENRGs associated with RIF were identified, with a focus on 6 key genes (MLKL, FASLG, XIAP, CASP1, BIRC3, and TLR3) implicated in necroptosis and immune processes. These genes were used to develop a predictive model for RIF, which was validated in 2 datasets. The model and TF network analysis underscored the importance of TLR3. Immune infiltration analysis showed reduced levels of 16 immune cells in RIF patients, highlighting immune system alterations. Several drugs targeting CASP1, such as nivocasan and emricasan, were identified as potential treatments. The study sheds light on the role of necroptosis in RIF, identifying key genes and immune alterations that could serve as biomarkers and therapeutic targets. These findings pave the way for future experimental research and clinical applications targeting necroptosis in RIF treatment.

Ineffectiveness of Crizotinib in a Non-Small-Cell Lung Cancer with Novel ALK- LIMS1 Fusion: A Case Report.

Anaplastic lymphoma kinase (ALK) rearrangements have been reported in 3-7% of non-small-cell lung cancers (NSCLC). ALK has been reported to be fused with a variety of genes in NSCLC. Significant clinical activity was achieved by ALK inhibitors in patients with NSCLC harbouring ALK translocations. We reported on a 48-year-old male Chinese patient with advanced lung adenocarcinoma harboring a novel ALK-LIMS1 who showed no response to crizotinib. The tissue was assayed by immunohistochemistry (IHC) for ALK and showed diffuse expression of ALK. Next-generation sequencing (NGS) was performed on the peripheral blood and tissue. The previous tumor tissue showed diffuse expression of ALK. Tissue and the later peripheral blood revealed a ALK- LIMS1 fusion. The patient failed to benefit from crizotinib (250 mg, twice a day), with a progression-free survival of two months. We identified a new ALK-LIMS1 fusion from an advanced lung adenocarcinoma which was primary resistant to crizotinib. Our case suggested that the coexistence of mutations and the non-dominant clone, as well as the rearrangement of ALK fusion, did not result in expressed ALK kinase domain that might lead to no response to ALK-TKIs.

Maternal preterm birth prediction in the United States: a case-control database study.

BACKGROUND: Preterm birth is serious public health worldwide, and early prediction of preterm birth in pregnant women may provide assistance for timely intervention and reduction of preterm birth. This study aimed to develop a preterm birth prediction model that is readily available and convenient for clinical application. METHODS: Data used in this case-control study were extracted from the National Vital Statistics System (NVSS) database between 2018 and 2019. Univariate and multivariate logistic regression analyses were utilized to find factors associated with preterm birth. Odds ratio (OR) and 95% confidence interval (CI) were used as effect measures. The area under the curve (AUC), accuracy, sensitivity, and specificity were utilized as model performance evaluation metrics. RESULTS: Data from 3,006,989 pregnant women in 2019 and 3,039,922 pregnant women in 2018 were used for the model establishment and external validation, respectively. Of these 3,006,989 pregnant women, 324,700 (10.8%) had a preterm birth. Higher education level of pregnant women [bachelor (OR = 0.82; 95%CI, 0.81-0.84); master or above (OR = 0.82; 95%CI, 0.81-0.83)], pre-pregnancy overweight (OR = 0.96; 95%CI, 0.95-0.98) and obesity (OR = 0.94; 95%CI, 0.93-0.96), and prenatal care (OR = 0.48; 95%CI, 0.47-0.50) were associated with a reduced risk of preterm birth, while age ≥ 35 years (OR = 1.27; 95%CI, 1.26-1.29), black race (OR = 1.26; 95%CI, 1.23-1.29), pre-pregnancy underweight (OR = 1.26; 95%CI, 1.22-1.30), pregnancy smoking (OR = 1.27; 95%CI, 1.24-1.30), pre-pregnancy diabetes (OR = 2.08; 95%CI, 1.99-2.16), pre-pregnancy hypertension (OR = 2.22; 95%CI, 2.16-2.29), previous preterm birth (OR = 2.95; 95%CI, 2.88-3.01), and plurality (OR = 12.99; 95%CI, 12.73-13.24) were related to an increased risk of preterm birth. The AUC and accuracy of the prediction model in the testing set were 0.688 (95%CI, 0.686-0.689) and 0.762 (95%CI, 0.762-0.763), respectively. In addition, a nomogram based on information on pregnant women and their spouses was established to predict the risk of preterm birth in pregnant women. CONCLUSIONS: The nomogram for predicting the risk of preterm birth in pregnant women had a good performance and the relevant predictors are readily available clinically, which may provide a simple tool for the prediction of preterm birth.

Long-term fertilization altered microbial community structure in an aeolian sandy soil in northeast China.

Soil microorganisms play crucial roles in nutrient cycling and determining soil quality and fertility; thus, they are important for agricultural production. However, the impacts of long-term fertilization on soil microbial community remain ambiguous due to inconsistent results from different studies. The objective of this study was to characterize changes in bacterial and fungal diversity and community structures after 12 years of different fertilization in aeolian sandy soil by analyzing 16S rRNA and ITS rRNA gene sequences and the soil properties to discover the driving factors. Eight different fertilizer treatments have been set up since 2009: no fertilizer (CK), chemical N fertilizer (N), chemical N and P fertilizer (NP), chemical N, P and K fertilizer (NPK), pig manure only (M), pig manure plus chemical N fertilizer (MN), pig manure plus chemical N and P fertilizer (MNP), pig manure plus chemical N, P, and K fertilizer (MNPK). The results indicated that the long-term application of chemical fertilizer reduced soil pH, whereas the addition of pig manure alleviated a decrease in soil pH value. Chemical fertilizer plus pig manure significantly improved soil available nutrients and soil organic carbon. Long-term MNPK fertilization resulted in changes in bacterial diversity due to effects on specific bacterial species; by contrast, all fertilization treatments resulted in changes in fungal diversity due to changes in soil properties. Principal component analysis indicated that fertilization had a significant effect on soil microbial community structure, and the effect of chemical fertilizer combined with pig manure was greater than that of chemical fertilizer alone. Soil available phosphorus, total phosphorus, and pH were the most important factors that influenced bacterial taxa, whereas soil pH, total phosphorus, organic carbon, ammonium nitrogen and nitrate nitrogen were the most important factors influencing fungal taxa after 12 years of fertilization in aeolian sandy soil.

Redefining the N-Terminal Regulatory Region of the Ca2+/H+ Antiporter CAX1 in Tomato.

Calcium (Ca2+) is an essential plant nutrient, and Ca2+/H+ exchangers (CAXs) regulate Ca2+ partitioning between subcellular compartments. AtCAX1 activity is inhibited by its N-terminal regulatory region (NRR), which was initially defined as the sequence between the first two methionines. However, the accuracy of this NRR definition and the NRR regulatory mechanism remain unclear. Here, using tomato SlCAX1 as a model, we redefined the NRR of CAXs and demonstrated that our new definition is also applicable to Arabidopsis AtCAX1 and AtCAX3. The N-terminal-truncated SlCAX1 (SlCAX1Δ39) but not the full-length SlCAX1 was active in yeast, similar to Arabidopsis AtCAX1. Characterization of slcax1 mutants generated by CRISPR-Cas9 confirmed the calcium transport ability of SlCAX1. Sequence alignment between SlCAX1, AtCAX1, AtCAX3, and the Bacillus subtilis Ca2+/H+ antiporter protein YfkE revealed that SlCAX1 does not have the 2nd methionine and YfkE does not have any amino acid residues in front of the first transmembrane domain. Truncating the amino acid residues up to the first transmembrane of SlCAX1 (SlCAX1Δ66) further increased its activity. The same truncation had a similar effect on Arabidopsis AtCAX1 and AtCAX3. Expression of full-length SlCAX1 and SlCAX1Δ66 in tomato plants confirmed the results. Our results suggest that SlCAX1 is critical for Ca2+ homeostasis and all the amino acid residues in front of the first transmembrane domain inhibit the activity of CAXs. Our redefinition of the NRR will facilitate fine-tuning of Ca2+ partitioning to reduce the incidence of Ca2+-related physiological disorders in crops.

Effect of Eye Movement Training on Sleep Quality of Patients with Advanced Lung Cancer Based on Pittsburgh Sleep Quality Index.

OBJECTIVE: To explore the effect of eye movement training on sleep quality of patients with advanced lung cancer based on the Pittsburgh Sleep Quality Index (PSQI). METHODS: 120 advanced lung cancer patients admitted to our hospital from January 2019 to January 2020 were selected as the research object and divided into group A (PSQI scores ≥ 10 points, n = 60) and group B (PSQI < 10 points, n = 60). Routine nursing was performed to both groups, and patients in group A received the eye movement training additionally, so as to compare their PSQI scores, negative emotion scores, adverse reaction rate (ARR), Cancer Coping Modes Questionnaire (CCMQ) scores, and pain scores. RESULTS: After training, group A obtained significantly better sleep quality (P < 0.05), lower negative emotion scores (P < 0.001), lower ARR (P < 0.05), better CCMQ scores (P < 0.05), and lower pain scores (P < 0.001) than group B. CONCLUSION: Eye movement training should be promoted in practice because it can reduce negative emotions, alleviate pain sensation, improve sleep quality and body condition, and lower the ARR for advanced lung cancer patients.

[Restrictive use of episiotomy for low forceps delivery].

OBJECTIVE: To explore the restrictive use of episiotomy for low forceps delivery. METHODS: A total of 311 low forceps delivery women at ≥37 weeks of gestation with live singleton cephalic pregnancies were recruited from June 2013 to December 2013 at our hospital. Among whom, 117 women underwent no episiotomy another 194 had mediolateral episiotomy. The maternal and neonatal outcomes of two types of episiotomy were compared. RESULTS: The amount of intra and post-partum hemorrhage, I-II perineal tearing, time of perineal suturing, perineal pain severity of post-partum 24 h significantly decreased than control group (P<0.05). No statistical significant inter-group differences existed in perineal hematoma, postnatal infection, urinary retention or length of stay after childbirth (P>0.05). And no statistically significant inter-group differences existed in incidence rates of neonatal asphyxia, neonatal birth trauma and newborns into neonatal intensive care unit (NICU) (P>0.05). CONCLUSION: During low forceps delivery, restrictive use of episiotomy may decrease the rate of episiotomy, reduce the amount of hemorrhage, minimize maternal injury, relieve pain and have no adverse effects on neonatal morbidities. And it improves the quality of vaginal delivery and demonstrate the concept of mini-invasiveness so that it is worthy of wider promotions.

[Study on the heterogeneity of edema in severe preeclampsia].

OBJECTIVE: The aim of this study was to analysis the clinical edema forms and explore the heterogeneity of edema in severe preeclampsia (PE) . METHOD: From February 2002 to February 2009, Peking University Third Hospital admitted with severe preeclampsia 228 cases who were enrolled in this study. The form is divided into no edema (A-type), pure interstitial edema (B-type), a simple cavity gap edema (C-type) and mixed interstitial edema that coexist with lacunar edema (D-type). Analysis and comparison of various types of edema in patients with different clinical manifestations of prenatal care models, laboratory parameters, the incidence of gestational age, complications and obstetric and perinatal outcomes, and analyze the relationship between different types of edema and albumins and the peak value of proteinuria. RESULTS: Edema was seen in 86% (197/228) of all of cases. Compared the cases who have regular prenatal care with those who have irregular care, differences were statistically significant in edema type composition ratio (P < 0.01) and the incidence of serious complications (P < 0.01), and serum albumin levels (P < 0.01), but not in the peak value of proteinuria (P > 0.05); Compared early-onset PE and late-onset PE patients, differences were statistically significant in edema type composition ratio (P < 0.01) and peak value of proteinuria (P < 0.01), but not in serum albumin levels and the incidence of serious complications (P > 0.05). Comparison between the various types of edema, differences were statistically significant in serum albumin levels and peak value of proteinuria and incidence of serious complications and the gestational week at PE onset and the incidence of treatment preterm labor (P < 0.05).Occurrence of placental abruption, heart failure and HELLP syndrome had statistical significance in different types of edema(P < 0.05). The varying degrees of interstitial edema were correlated with serum albumin levels (r = -0.19, P < 0.05) and serious complication occurrence (r = -0.232, P < 0.05), but no correlation displayed with the peak value of urinary protein (P > 0.05). CONCLUSIONS: The manifestations of edema were diverse in severe preeclampsia. The forms of edema were related to the PE onset of gestational age and serious complication involving in different organs.Strengthen prenatal care and early detection of edema may improve adverse obstetric outcomes.

[Early warning signs of severe preeclampsia].

OBJECTIVE: To identify the early warning signs of severe preeclampsia (SPE). METHODS: A case-control (1:2) observational study was conducted. Forty-seven pregnant women with SPE, who attended the prenatal clinics of Peking University Third Hospital regularly from Jan. 2002 to Dec. 2007, were selected as the study group, including 12 early onset and 35 late onset ones. The control group consisted of 94 healthy singleton pregnant women at the same period. Clinical data were collected and analyzed. RESULTS: (1) The basal body mass index (BMI) showed no difference between the study and control group [(23.27 +/- 4.31) kg/m(2) vs (21.52 +/- 3.09) kg/m(2), P > 0.05]. (2) The net increase of BMI in the study group before the onset of SPE was higher than that in the control [(5.60 +/- 2.17) kg/m(2) vs (4.85 +/- 1.52) kg/m(2), P < 0.05] and the increase of BMI per week was also higher [(0.74 +/- 0.41) kg/(m(2).w)(-1) vs (0.23 +/- 0.18) kg/(m(2).w)(-1), P < 0.01]. The sensitivity and specificity of BMI increase per week in predicting SPE was 84% and 81% at a cut-off value of 0.39 kg/(m(2).w)(-1), respectively, and 79% and 91% at 0.41 kg/(m(2).w)(-1) correspondingly. (3) During the third trimester and before the onset of SPE, the weight gain per week in the study group was higher than that of the control [(0.93 +/- 0.70) kg vs (0.63 +/- 0.20) kg, P < 0.01]. Significant difference was also found in the net weight gain between the two groups (P < 0.01), but not in the percentage of women with excessive weight gain (> 0.50 kg/w) [60% (25/42) in the study group vs 63% (53/84) in the control group, P > 0.05]. (4) Higher percentage of women experienced pre-hypertension in the study group than in the controls [17% (8/47) vs 5% (5/94), P < 0.01]. (5) In the study group, 53% (25/47) of the women had edema before SPE onset, but the figure dropped to 18% (17/94) in the controls (P < 0.01). (6) Eight women in the study group and one in the control group suffered from hypoproteinemia before SPE onset with the average level of plasma albumin of (32.6 +/- 1.6) g/L and (38.4 +/- 2.1) g/L (P < 0.01), respectively. (7) Proteinuria was reported in 10 cases (21%) in the study group and 4 (4%) in the controls (P < 0.01). (8) Logistic regression analysis showed that the risk factors for SPE included edema (OR = 6.16, 95%CI: 2.29 - 16.57), pre-hypertension (OR = 6.21, 95%CI: 1.56 - 24.77), proteinuria (OR = 9.68, 95%CI: 1.86 - 50.30), and weight gain > 0.85 kg/w during the third trimester (OR = 11.60, 95%CI: 3.54 - 37.97). CONCLUSIONS: Edema, excessive weight gain, pre-hypertension and hypoproteinemia are early warning signs of SPE. Pregnant women with the above signs required close monitoring during prenatal care.