The safety of maxillary sinus floor elevation and the accuracy of implant placement using dynamic navigation.

OBJECTIVE: To date, it remains a challenge to conduct maxillary sinus floor elevation (MSFE) owing to heterogeneity of anatomical structures and limited operative visibility of the maxillary sinus. The aim of this study is to investigate the safety of MSFE and the accuracy of implant placement using dynamic navigation. METHODS: Forty-two implants were placed in thirty-five patients requiring implantation in posterior maxilla with dynamic navigation. They were assigned to either lateral window sinus floor elevation (LWSFE) group (n = 22) or transcrestal sinus floor elevation (TSFE) group (n = 20) according to the residual alveolar bone height (RBH). Platform deviation, apex deviation and angular deviation between actual and planned implant placement were measured in precision evaluation software. Three deviations of two groups were compared via SPSS 22.0 software. RESULTS: Neither accidental bleeding nor perforation of Schneiderian membrane occurred in any patients. The actual window position of LWSFE was consistent with the preoperative design. There were no significant differences in platform, apex and angular deviations between the two groups (P > 0.05). CONCLUSION: In this study the dynamic navigation harvested clinically acceptable safety of MSFE and accuracy for implant placement in posterior maxillary region. The dynamic navigation would provide the clinician with assistance in achieving precise preoperative planning and reducing complications in surgical procedures. The granular bone grafts used in the LWSFE did not significantly affection on the accuracy of the simultaneous implant placement under the guidance of dynamic navigation.

Hydrogel-Transformable Antioxidant Poly-γ-Glutamic Acid/Polyethyleneimine Hemostatic Powder for Efficient Wound Hemostasis.

Hemostatic powder, which can absorb large amounts of water and tends to produce repeated hydration with tissue, has been clinically proven as an ideal engineering material for treating wounds and tissues. We herein designed a polypeptide-based hemostatic powder. A water-soluble polypeptide, γ-polyglutamic acid (γ-PGA), was mixed with the polyethyleneimine (PEI), N-hydroxysuccinimide, and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide. The solution of these polymers was lyophilized to harvest the γ-PGA/PEI powder (PP hemostatic powder). When deposited on a bleeding wound, the PP hemostatic powder can quickly absorb a large amount of blood and interstitial fluid, concentrate coagulation factors, coagulate blood cells, and eventually form a stable mechanical hydrogel. The wound bleeding time of the PP hemostatic powder group was 1.8 ± 0.4 min, significantly lower than that of the commercial chitosan hemostatic powder group (2.8 ± 0.4 min). The PP hemostatic powder was endowed with antioxidant capacity by introducing protocatechuic aldehyde, which can effectively inhibit inflammation and promote wound healing. Therefore, via preparation through a facile lyophilization method, the PP hemostatic powder is expected to find a wide application prospect as a qualified hemostatic powder.

Involvement of HIF1 stabilization and VEGF signaling modulated by Grx-1 in murine model of bronchopulmonary dysplasia.

Hypoxia inducible factor (HIF)-1α could be stabilized by Grx1 deletion, which is implicated critical in the pathogenesis of bronchopulmonary dysplasia (BPD). Until now, the stabilization of HIF-1α by glutathionylation to regulate the pulmonary microcirculation in BPD is not well addressed. In this study, we investigated whether the HIF-1α stabilization modulated by Grx1 ablation could ameliorate the pathological changes in the mouse model of BPD, including angiogenesis and alveolar formation. We found that depletion of Grx1 increased levels of GSH-protein adducts, which was associated with the improvement in the numbers of alveoli, the capillary density in the pulmonary microcirculation and the survival rate in the littermates with hyperoxic exposure. Grx1 ablation could promote HIF-1α glutathionylation by increasing GSH adducts to stabilize HIF-1α and to induce VEGF-A production in the lung tissue. The above phenotype of capillary density and VEGF-A production was removed by the pharmacological administration of YC-1, the HIF-1α inhibitor, suggesting the HIF-1α dependent manner for pulmonary microcirculatory perfusion. These data indicate that HIF-1α stabilization plays an critical role in modification pulmonary microcirculatory perfusion, which is associated with the pathological damage under hyperoxic conditions, suggesting that targeting with HIF-1α stabilization should be a potential clinical and therapeutic strategy for BPD treatment.

The fecal microbiota of gravidas with fetal growth restriction newborns characterized by metagenomic sequencing.

BACKGROUND: Fetal growth restriction (FGR) is a complex obstetric complication with various causes and of great harm. However, the specific pathogenesis of FGR is unclear, which limits its effective treatment. Gut microbiota dysbiosis was found to be important in pathogenesis of various diseases. However, its role in FGR development remains unclear and needs to be clarified. METHODS: In our case-control study, we recruited eight FGR and eight control female participants and collected their fecal samples in third trimester before delivery. We performed metagenomic sequencing and bioinformatic analysis to compare the gut microbiota composition and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between the two groups. RESULTS: Our results showed that totally 20 gut microbes were significantly different between two groups (p<0•05), and the correlation analysis found that g__Roseomonas and g__unclassified_f__Propionibacteriaceae were significantly positive correlated with both maternal body mass index (BMI) before delivery, placental weight, and neonatal birth weight (BW) percentile (all p<0•05), while g__Marinisporobacter and g__Sphingomonas were significantly negative correlated with both neonatal BMI and neonatal BW percentile (all p<0•05). Through KEGG pathway analysis, we found that the abundance of the Nitrogen metabolism pathway decreased significantly (p<0•05) whereas the abundance of the Amoebiasis pathway increased significantly in the FGR group (p<0•05). CONCLUSION: In this study, we demonstrated that the occurrence of FGR is associated with the change of gut microbiota of pregnant women.

Maternal Prenatal Inflammation Increases Brain Damage Susceptibility of Lipopolysaccharide in Adult Rat Offspring via COX-2/PGD-2/DPs Pathway Activation.

A growing body of research suggests that inflammatory insult contributes to the etiology of central nervous system diseases, such as depression, Alzheimer's disease, and so forth. However, the effect of prenatal systemic inflammation exposure on offspring brain development and cerebral susceptibility to inflammatory insult remains unknown. In this study, we utilized the prenatal inflammatory insult model in vivo and the neuronal damage model in vitro. The results obtained show that prenatal maternal inflammation exacerbates LPS-induced memory impairment, neuronal necrosis, brain inflammatory response, and significantly increases protein expressions of COX-2, DP2, APP, and Aß, while obviously decreasing that of DP1 and the exploratory behaviors of offspring rats. Meloxicam significantly inhibited memory impairment, neuronal necrosis, oxidative stress, and inflammatory response, and down-regulated the expressions of APP, Aß, COX-2, and DP2, whereas significantly increased exploring behaviors and the expression of DP1 in vivo. Collectively, these findings suggested that maternal inflammation could cause offspring suffering from inflammatory and behavioral disorders and increase the susceptibility of offspring to cerebral pathological factors, accompanied by COX-2/PGD-2/DPs pathway activation, which could be ameliorated significantly by COX-2 inhibitor meloxicam treatment.

[Comparison of shaping ability of 4 nickel-titanium rotary instruments in preparation of curved root canals].

PRUPOSE: To compare the shaping ability of 4 nickel-titanium rotary instruments in preparation of curved root canals. METHODS: Forty extracted human maxillary first or second molars with mesiobuccal root canal curvature ranging from 20°-40° were selected. The teeth were randomly equally divided into 4 groups(n=10). Mesial root canals were separately prepared using Protaper Universal, Protaper Next, TF, and S3 nickel-titanium instruments. A series of preoperative and postoperative images were taken by Micro-CT． Mimics 17.0 software was used to analyze the following parameters: canal transportation, centering ratio values, root canal volume, volume of removed dentin, and canal/root width ratio. Data analysis was performed by using SPSS 20.0 software package. RESULTS: In terms of canal transportation after preparation at 1, 3 and 5 mm from the apex, Protaper Universal was more than the other three groups(P＜0.05). The centering ratio value of Protaper Universal was significantly smaller than that of the other three groups at 1 mm from the apex(P＜0.05). The amount of dentin removal was significantly different after instrumentation with the four test systems(P＜0.05). Protaper Universal had the highest mean volume of removed dentin. After preparation, all root canals had a diameter that was not larger than 39% of the root diameter at the coronal and middle segments. CONCLUSIONS: Under the conditions of this study, Protaper Next, TF, S3 systems seem to be better choices than Protaper Universal system in preparing curved root canals.

Maternal Inflammation Exaggerates Offspring Susceptibility to Cerebral Ischemia-Reperfusion Injury via the COX-2/PGD2/DP2 Pathway Activation.

The pathogenesis of cerebral ischemia-reperfusion (I/R) injury is complex and does not exhibit an effective strategy. Maternal inflammation represents one of the most important factors involved in the etiology of brain injury in newborns. We aimed to investigate the effect of maternal inflammation on offspring susceptibility to cerebral I/R injury and the mechanisms by which it exerts its effects. Pregnant SD rats were intraperitoneally injected with LPS (300 µg/kg/day) at gestational days 11, 14, and 18. Pups were subjected to MCAO/R on postnatal day 60. Primary neurons were obtained from postnatal day 0 SD rats and subjected to OGD/R. Neurological deficits, brain injury, neuronal viability, neuronal damage, and neuronal apoptosis were assessed. Oxidative stress and inflammation were evaluated, and the expression levels of COX-2/PGD2/DP pathway-related proteins and apoptotic proteins were detected. Maternal LPS exposure significantly increased the levels of oxidative stress and inflammation, significantly activated the COX-2/PGD2/DP2 pathway, and increased proapoptotic protein expression. However, maternal LPS exposure significantly decreased the antiapoptotic protein expression, which subsequently increased neurological deficits and cerebral I/R injury in offspring rats. The corresponding results were observed in primary neurons. Moreover, these effects of maternal LPS exposure were reversed by a COX-2 inhibitor and DP1 agonist but exacerbated by a DP2 agonist. In conclusion, maternal inflammatory exposure may increase offspring susceptibility to cerebral I/R injury. Moreover, the underlying mechanism might be related to the activation of the COX-2/PGD2/DP2 pathway. These findings provide a theoretical foundation for the development of therapeutic drugs for cerebral I/R injury.

Characterization of E-cadherin expression in normal mucosa, dysplasia and adenocarcinoma of gastric cardia and its influence on prognosis.

BACKGROUND: Gastric cardia adenocarcinoma (GCA), which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries, is of similar geographic distribution with esophageal squamous cell carcinoma in China, and even referred as "sister cancer" by Chinese oncologists. The molecular mechanism for GCA is largely unknown. Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers. However, the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis. AIM: To characterize E-cadherin expression in normal gastric cardia mucosa, dysplasia and GCA tissues, and its influence on prognosis for GCA. METHODS: A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases. The enrollment criteria included radical surgery for GCA, but without any radio- or chemo-therapy before operation. The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue (n = 208) and dysplasia lesions (n = 156) were collected, and processed as tissue microarray for immunohistochemistry. The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter, telephone or home interview. E-cadherin protein expression was determined by two step immunohistochemistry. Kaplan-Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients. RESULTS: Of the 4561 GCA patients, there were 3607 males with a mean age of 61.6 ± 8.8 and 954 females with a mean age of 61.9 ± 8.6 years, respectively. With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA, the positive immunostaining rates for E-cadherin decreased significantly from 100% to 93.0% and 84.1%, respectively (R2 = 0.9948). Furthermore, E-cadherin positive immunostaining rate was significantly higher in patients at early stage (0 and I) than in those at late stage (II and III) (92.7% vs 83.7%, P = 0.001). E-cadherin positive expression rate was significantly associated with degree of differentiation (P = 0.001) and invasion depth (P < 0.001). Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative (P = 0.026). It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis. However, in patients with negative lymph node metastasis, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.036). Similarly, in patients with late stage GCA, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.011). CONCLUSION: E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.

Long-term effect of hospital volume on the postoperative prognosis of 158,618 patients with esophageal squamous cell carcinoma in China.

Background: The impact of hospital volume on the long-term survival of esophageal squamous cell carcinoma (ESCC) has not been well assessed in China, especially for stage I-III stage ESCC. We performed a large sample size study to assess the relationships between hospital volume and the effectiveness of ESCC treatment and the hospital volume value at the lowest risk of all-cause mortality after esophagectomy in China. Aim: To investigate the prognostic value of hospital volume for assessing postoperative long-term survival of ESCC patients in China. Methods: The date of 158,618 patients with ESCC were collected from a database (1973-2020) established by the State Key Laboratory for Esophageal Cancer Prevention and Treatment, the database includes 500,000 patients with detailed clinical information of pathological diagnosis and staging, treatment approaches and survival follow-up for esophageal and gastric cardia cancers. Intergroup comparisons of patient and treatment characteristics were conducted with the X2 test and analysis of variance. The Kaplan-Meier method with the log-rank test was used to draw the survival curves for the variables tested. A Multivariate Cox proportional hazards regression model was used to analyze the independent prognostic factors for overall survival. The relationship between hospital volume and all-cause mortality was assessed using restricted cubic splines from Cox proportional hazards models. The primary outcome was all-cause mortality. Results: In both 1973-1996 and 1997-2020, patients with stage I-III stage ESCC who underwent surgery in high volume hospitals had better survival than those who underwent surgery in low volume hospitals (both P<0.05). And high volume hospital was an independent factor for better prognosis in ESCC patients. The relationship between hospital volume and the risk of all-cause mortality was half-U-shaped, but overall, hospital volume was a protective factor for esophageal cancer patients after surgery (HR<1). The concentration of hospital volume associated with the lowest risk of all-cause mortality was 1027 cases/year in the overall enrolled patients. Conclusion: Hospital volume can be used as an indicator to predict the postoperative survival of ESCC patients. Our results suggest that the centralized management of esophageal cancer surgery is meaningful to improve the survival of ESCC patients in China, but the hospital volume should preferably not be higher than 1027 cases/year. Core tip: Hospital volume is considered to be a prognostic factor for many complex diseases. However, the impact of hospital volume on long-term survival after esophagectomy has not been well evaluated in China. Based on a large sample size of 158,618 ESCC patients in China spanning 47 years (1973-2020), We found that hospital volume can be used as a predictor of postoperative survival in patients with ESCC, and identified hospital volume thresholds with the lowest risk of death from all causes. This may provide an important basis for patients to choose hospitals and have a significant impact on the centralized management of hospital surgery.

Advances in Hemostatic Hydrogels That Can Adhere to Wet Surfaces.

Currently, uncontrolled bleeding remains a serious problem in emergency, surgical and battlefield environments. Despite the specific properties of available hemostatic agents, sealants, and adhesives, effective hemostasis under wet and dynamic conditions remains a challenge. In recent years, polymeric hydrogels with excellent hemostatic properties have received much attention because of their adjustable mechanical properties, high porosity, and biocompatibility. In this review, to investigate the role of hydrogels in hemostasis, the mechanisms of hydrogel hemostasis and adhesion are firstly elucidated, the adhesion design strategies of hemostatic hydrogels in wet environments are briefly introduced, and then, based on a comprehensive literature review, the studies and in vivo applications of wet-adhesive hemostatic hydrogels in different environments are summarized, and the improvement directions of such hydrogels in future studies are proposed.

Development and validation of a prognostic nomogram model for Chinese patients with primary small cell carcinoma of the esophagus.

BACKGROUND: Primary small cell carcinoma of the esophagus (PSCE) is a highly invasive malignant tumor with a poor prognosis compared with esophageal squamous cell carcinoma. Due to the limited samples size and the short follow-up time, there are few reports on elucidating the prognosis of PSCE, especially on the establishment and validation of a survival prediction nomogram model covering general information, pathological factors and specific biological proteins of PSCE patients. AIM: To establish an effective nomogram to predict the overall survival (OS) probability for PSCE patients in China. METHODS: The nomogram was based on a retrospective study of 256 PSCE patients. Univariate analysis and multivariate Cox proportional hazards regression analysis were used to examine the prognostic factors associated with PSCE, and establish the model for predicting 1-, 3-, and 5-year OS based on the Akaike information criterion. Discrimination and validation were assessed by the concordance index (C-index) and calibration curve and decision curve analysis (DCA). Histology type, age, tumor invasion depth, lymph node invasion, detectable metastasis, chromogranin A, and neuronal cell adhesion molecule 56 were integrated into the model. RESULTS: The C-index was prognostically superior to the 7th tumor node metastasis (TNM) staging in the primary cohort [0.659 (95%CI: 0.607-0.712) vs 0.591 (95%CI: 0.517-0.666), P = 0.033] and in the validation cohort [0.700 (95%CI: 0.622-0.778) vs 0.605 (95%CI: 0.490-0.721), P = 0.041]. Good calibration curves were observed for the prediction probabilities of 1-, 3-, and 5-year OS in both cohorts. DCA analysis showed that our nomogram model had a higher overall net benefit compared to the 7th TNM staging . CONCLUSION: Our nomogram can be used to predict the survival probability of PSCE patients, which can help clinicians to make individualized survival predictions.

Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma.

The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients.

Inflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages.

Candida albicans is the most common cause of fungal sepsis. Inhibition of inflammasome activity confers resistance to polymicrobial and LPS-induced sepsis; however, inflammasome signaling appears to protect against C. albicans infection, so inflammasome inhibitors are not clinically useful for candidiasis. Here we show disruption of GSDMD, a known inflammasome target and key pyroptotic cell death mediator, paradoxically alleviates candidiasis, improving outcomes and survival of Candida-infected mice. Mechanistically, C. albicans hijacked the canonical inflammasome-GSDMD axis-mediated pyroptosis to promote their escape from macrophages, deploying hyphae and candidalysin, a pore-forming toxin expressed by hyphae. GSDMD inhibition alleviated candidiasis by preventing C. albicans escape from macrophages while maintaining inflammasome-dependent but GSDMD-independent IL-1ß production for anti-fungal host defenses. This study demonstrates key functions for GSDMD in Candida's escape from host immunity in vitro and in vivo and suggests that GSDMD may be a potential therapeutic target in C. albicans-induced sepsis.

Preoperative maximal voluntary ventilation, hemoglobin, albumin, lymphocytes and platelets predict postoperative survival in esophageal squamous cell carcinoma.

BACKGROUND: Preoperative pulmonary function plays an important role in selecting surgical candidates and assessing postoperative complications. Reduced pulmonary function is associated with poor survival in several cancers, but the prognostic value of preoperative pulmonary function in esophageal squamous cell carcinoma (ESCC) is unclear. Nutritional and systemic inflammation parameters are vital to cancer survival, and the combination of these parameters improves the prognostic value. The hemoglobin, albumin, lymphocytes and platelets (HALP) score is a novel prognostic indicator to reflect the nutritional and inflammation status, but the clinical effects of the HALP score combined with maximal voluntary ventilation (MVV), an important parameter of pulmonary function, have not been well studied in ESCC. AIM: To investigate the prognostic value of MVV and HALP score for assessing postoperative survival of ESCC patients. METHODS: Data from 834 ESCC patients who underwent radical esophagectomy with R0 resection were collected and retrospectively analyzed. Preoperative MVV and HALP data were retrieved from medical archives. The HALP score was calculated by the formula: Hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)/platelets (/L). The optimal cut-off values of MVV and HALP score were calculated by the receiver operating characteristic curve analysis. The Kaplan-Meier method with log-rank test was used to draw the survival curves for the variables tested. Multivariate Cox proportional hazard regression models were used to analyze the independent prognostic factors for overall survival. RESULTS: MVV was significantly associated with gender (P < 0.001), age at diagnosis (P < 0.001), smoking history (P < 0.001), drinking history (P < 0.001), tumor length (P = 0.013), tumor location (P = 0.037) and treatment type (P = 0.001). The HALP score was notably associated with gender (P < 0.001), age at diagnosis (P = 0.035), tumor length (P < 0.001) and invasion depth (P = 0.001). Univariate Cox regression analysis showed that low MVV and low HALP score were associated with worse overall survival (all P < 0.001). Multivariate analysis showed that low MVV and the HALP score were both independent risk factors for overall survival (all P < 0.001). The combination of MVV and HALP score improved the prediction performance for overall survival than tumor-node-metastasis. Also, low combination of MVV and HALP score was an independent risk factor for poor overall survival (P < 0.001). CONCLUSION: MVV, HALP score and their combination are simple and promising clinical markers to predict overall survival of ESCC patients.

Comparative Pharmacokinetic Study of Hesperetin after Oral Administration in Normal and Hyperuricemia Rats by UPLC-MS/MS.

BACKGROUND: Hesperetin has antihyperuricemia activity, and the pharmacokinetic profiles of hesperetin may be altered by hyperuricemia. This study aimed to develop a highly sensitive and specific method for the determination of hesperetin in normal and hyperuricemia rats, and to compare pharmacokinetic profiles of hesperetin after oral administration between normal and hyperuricemia rats. METHODS: Sprague-Dawley (SD) rats were randomly divided into one normal group (group A) and four hyperuricemia groups (group B, C, D, and E). Groups A, B, C, and D received a single dose (9-81 mg/kg) of hesperetin on Day 28, respectively, while group E received multiple doses (27 mg/kg) of hesperetin once daily for 28 days. Blood samples were collected at 10 different time points post-dose, and hesperetin was determined by Ultra-high Performance Liquid Chromatography- tandem Mass Spectrometric (UPLC-MS/MS). RESULTS: Compared with normal condition of group A, hyperuricemia of group C induced 48.19% and 19.57% decreases in Cmax and CL/F, and resulted in 58.25% and 19.48% increases in Tmax and AUC0-t for hesperetin, respectively. After 28 days of hesperitin treatment, Cmax of group E was significantly elevated than that of group C (p < 0.05). Hesperetin exhibited nonlinear pharmacokinetic properties in the range of 9-81 mg/kg in hyperuricemia rats. CONCLUSION: The pharmacokinetic parameters of hesperetin in hyperuricemia rats were reported for the first time. Intestinal injury may be ameliorated by hesperetin in hyperuricemia rats after 28 days' treatment. These findings could provide more beneficial information to the mechanism and clinical applications of hesperetin.

Exploring the Molecular Mechanism and Biomarker of Recurrent Spontaneous Abortion Based on RNA Sequencing Analysis.

BACKGROUND: Recurrent spontaneous abortion (RSA) is defined as the failure of two or more consecutive clinical pregnancies before 20 weeks of gestation. It is a hot issue in contemporary obstetrics. The etiology of RSA is complicated. Exploring the molecular mechanisms of RSA will be helpful for the prevention and precise therapy at the molecular level. This study aimed to provide novel insights into the biological characteristics and related pathways of differentially expressed genes (DEGs) in RSA. METHODS: The data set GSE121950 was obtained from GEO data sets. We identified the DEGs using the affy pack-age in R programming software. Gene set enrichment analysis (GESA) and GenePattern tools were performed to examine the gene expression differences between RSA and control group. Protein-protein interaction (PPI) analysis was performed using STRING online tool (https://string-db.org/). qRT-PCR was carried out to validate the expression levels of DEGs in 16 villus tissue samples from patients with induced abortion and 16 villus tissue samples from RSA patients. RESULTS: A total of 628 DEGs with adjPval < 0.05 and |logFC| > 1 were obtained, including 155 up-regulated genes and 473 down-regulated genes. Ten gene ontology (GO) terms and 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were screened out by comparing the genome-wide gene set expression patterns of normal and RSA tissues. Eight genes involved in RSA were identified from the hippo signaling pathway, cytokine-cytokine receptor interaction pathway, and allograft rejection pathway. CONCLUSIONS: Present findings demonstrated that several cytokine regulation processes have a deep impact on RSA. A number of genes involved in the hippo signaling pathway, cytokine-cytokine receptor interaction pathway, and allograft rejection pathway may be critical mediators or participators in the pathogenesis of RSA. Although further in vivo and in vitro validations are required, our data may provide an important theoretical basis to elucidate the pathogenesis of RSA.

Copper nanoclusters@Al3+ complexes with strong and stable aggregation-induced emission for application in enzymatic determination of urea.

The aggregates of glutathione-capped CuNCs induced by Al3+ (named CuNCs@Al3+ complexes) show a stable aggregation-induced emission (AIE) for about 1 month. Their fluorescence maintains a high level in the pH range 4.0 to 7.0, while it quenches as pH increases from 7.0 to 7.7 or decreases from 4.0 to 3.0. Under urease-catalyzed hydrolysis, urea produces ammonia, which can be further hydrolyzed to yield OH-. This leads to a pH increase of the immediate environment. Hence, the CuNCs@Al3+ complexes are a suitable probe to determine urea. The fluorescence of CuNCs@Al3+ complexes quenches linearly at 585 nm with the excitation wavelength at 340 nm when the concentration of urea increases from 20 to 150 µM. The limit of detection (LOD) of urea is 5.86 µM. This sensitivity is superior to other reported works due to the narrow pH response range of CuNCs@Al3+ complexes. This method has been successfully applied for measuring urea in human urine samples with satisfactory recoveries. Graphic abstract Schematic representation of urea determination based on pH-responsive property of copper nanoclusters@Al3+ complexes. Ammonia is produced in the hydrolysis of urea by urease, and it is further hydrolyzed to yield OH-, leading to increasing pH of the environment.

Recombinant Human Elafin Ameliorates Chronic Hyperoxia-Induced Lung Injury by Inhibiting Nuclear Factor-Kappa B Signaling in Neonatal Mice.

The study aimed to investigate whether recombinant human elafin can prevent hyperoxia-induced pulmonary inflammation in newborn mice, and to explore the mechanism underlying the inhibitory effects of elafin on nuclear factor-kappa B (NF-κB) signaling pathway. Neonatal C57BL/6J mice were exposed to 85% O2 for 1, 3, 7, 14, or 21 days. Then, elafin was administered daily for 20 days through intraperitoneal injection. After treatment, morphometric analysis, quantitative real-time polymerase chain reaction, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and Western blotting were carried out to determine the key markers involved in inflammatory process and the potential signaling pathways in hyperoxia-exposed newborn mice treated with elafin. In neonatal bronchopulmonary dysplasia (BPD) mice, hyperoxia induced apoptosis by increasing Bcl-2-associated X protein expression, and triggered inflammation by upregulating the expression levels of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-α. Moreover, hyperoxia activated NF-κB signaling pathway by promoting the nuclear translocation of p65 in lung tissue. However, all these changes could be inhibited or reversed by elafin at least partially. Elafin reduced apoptosis, suppressed inflammation cytokines, and improved NF-κB p65 nuclear accumulation in hyperoxia-exposed neonatal mice, indicating that this recombinant protein can serve as a novel target for the treatment of BPD.

Characterization of 500 Chinese patients with cervical esophageal cancer by clinicopathological and treatment outcomes.

Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer (CEC), due to its rare clinical prevalence. Our objective was to determine the relationship between pathological characteristics, treatment protocols, and survival outcomes in Chinese CEC patients. Methods: A total of 500 Chinese CEC patients were selected from our 500,000 esophageal and gastric cardia carcinoma database (1973-2018). There were two main groups: patients treated with surgery, and patients receiving non-surgical treatments (radiotherapy, radiochemotherapy, and chemotherapy). The Chi-square test and Kaplan-Meier method were used to compare the continuous variables and survival. Results: Among the 500 CEC patients, 278 (55.6%) were male, and the median age was 60.9 ± 9.4 years. A total of 496 patients (99.2%) were diagnosed with squamous cell carcinoma. In 171 (34.2%) patients who received surgery, 22 (12.9%) had undergone laryngectomy. In 322 (64.4%) patients who received non-surgical treatments, 245 (76.1%) received radiotherapy. Stratified survival analysis showed that only T stage was related with survival outcomes for CEC patients in the surgical group, and the outcomes between laryngectomy and non-laryngectomy patients were similar. It was noteworthy that the 5-year survival rate was similar in CEC patients among the different groups treated with surgery, radiotherapy, chemotherapy, or radiochemotherapy (P = 0.244). Conclusions: The CEC patients had similar survival outcomes after curative esophagectomy and radiotherapy, including those with or without total laryngectomy. These findings suggest that radiotherapy could be the initial choice for treatment of Chinese CEC patients.