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Carbon fiber reinforced polymer (CFRP) has many advantages, such as light weight, high strength, and excellent corrosion resistance. In this paper, the experimental research of the square steel tube reinforced by carbon fiber reinforced polymer was performed, and its ultimate bearing capacity formula was derived. The tests were based on the previous results of our research group. Six sets of the test are performed by altering two-layer-CFRP and the eccentricity. The test results demonstrated that CFRP improved the ultimate bearing capacity of square steel tubes. As the number of layers of CFRP increased, the growth rate of bearing capacity gradually declined, and reinforcement of CFRP on specimens of large eccentricity was significantly effective than that of small eccentricity one. After longitudinal CFRP was stuck, a circumferential layer of CFRP in the middle of the square steel tube can improve the reinforcement effect. This paper referred to the existing codes and took the idea of area substitution to derive the ultimate bearing capacity formula of the steel tube reinforced by CFRP. The calculated values of the formula were compared with those of the experiment, and the difference is within the range, which proves the rationality of the derived formula.

Purpose This study aimed to investigate the risk factors related to the termination of pregnancy via cesarean section and establish a prediction model for cesarean section based on the characteristics of pregnant women.Patients and methods: The clinical characteristics of 2552 singleton pregnant women who delivered a live baby between January 2020 and December 2021 were retrospectively reviewed. These women were divided into vaginal delivery group (n = 1850) and cesarean section group (n = 802). Lasso regression analysis was employed to screen the independent risk factors of cesarean section. Multivariate logistic regression analysis was used to establish the prediction model, followed by delineation of nomogram, receiver operating characteristic curve (ROC), calibration curve, Decision Curve Analysis (DCA) and confusion matrix.Results There were 1850 women in the vaginal delivery group and 702 women in the cesarean section group. There were significant differences in the age and height of women, maternal weight at birth, pregestational weight, weight gain during pregnancy, gravida, weeks of pregnancy, use of assisted reproductive technology, abnormal blood glucose, hypertension disorders of pregnancy(HDP), scarred uterus, premature rupture of membrane༈PROM༉, placenta previa, floating head, abnormal fetal presentation, cord entanglement and labor analgesia between two groups (P Conclusion The logistic regression prediction model of cesarean section has favorable discrimination, accuracy and consistency and can be employed as a reference for clinicians to improve the outcomes of pregnant women and neonates.

Purpose. Mesenchymal stem cells (MSCs) and their derivant are among the promising treatments for intrauterine adhesion (IUA); they have been reported to repair the endometrial injury by proliferating endometrial cells. However, the signal pathways involved are not clear. This study investigated the role of human umbilical cord mesenchymal stem cell-derived conditioned medium (hUCMSC-CM) in relieving IUA to find out whether Wnt/β-catenin signaling was involved, and if so, to determine the possible ligands. Methods. After endometrial epithelial cells (EECs) were treated with hUCMSC-CM, their proliferation and migration were measured by the CCK8 assay and the scratch assay. The activation of Wnt/β-catenin signaling was measured by Western blots, fluorescent staining, and T-cell factor/lymphoid enhancer factor (TCF/LEF) luciferase. A Wnt inhibitor (XAV393) was used to inhibit the proliferation effect of hUCMSC-CM in EECs. Wnt5a expression in hUCMSC was measured by Western blots and fluorescent staining, and Wnt5a in hUCMSC-CM was detected by enzyme-linked immunosorbent assay (ELISA), to further clarify the mechanism. Results. As shown by the CCK8 assay, hUCMSC-CM promoted proliferation and migration of EECs. The expression of β-catenin, c-myc, and cyclin D1 increased in EECs after being treated with hUCMSC-CM. Moreover, hUCMSC-CM was found to promote β-catenin delivery into nuclei by Western blot and fluorescent staining; meanwhile, the inhibitor (XAV393) could restrain this process and inhibit the effect of hUCMSC-CM on EEC proliferation. Wnt5a was detected in hUCMSCs and hUCMSC-CM, which might be a potential therapeutic target. Conclusion. This study demonstrated that hUCMSC-CM promoted human endometrial cell proliferation through Wnt/β-catenin signaling, and Wnt5a might be a potential activator. This would be one of the activating signal pathways in the MSC-related treatment of IUA.

Do overweight/obese women with PCOS with different uric acid concentrations show different effects after a ketogenic diet intervention?The study involved women with PCOS with a body mass index (BMI) of ≥24 kg/mAfter 12 weeks of the ketogenic diet intervention, body weight (hyperuricaemia group: P=0.001; non-hyperuricaemia group: P0.001), BMI (hyperuricaemia group: P = 0.025; non-hyperuricaemia group: P0.001) and body fat percentage (hyperuricaemia group: P0.001; non-hyperuricaemia group: P0.001) were decreased in both groups. There was greater weight loss in the non-hyperuricaemia group (hyperuricaemia group 11.2±4.6 kg versus non-hyperuricaemia group 14.7±4.8 kg; P0.05). In the non-hyperuricaemia group, uric acid concentrations increased significantly after 6 weeks of the ketogenic diet intervention (week 0: 5.69±0.84 mg/dl versus week 6: 8.41 ± 2.33 mg/dl; P 0.001) and reached the concentrations of the hyperuricaemia group (week 6: 9.37 ± 2.43 mg/dl; P 0.05).A ketogenic diet intervention is beneficial for overweight/obese women with PCOS with different serum uric acid concentrations. Participants with normal basal uric acid concentrations showed a greater fluctuation of serum uric acid concentrations during the ketogenic diet intervention and had a greater weight loss.

Cysteine oxidation by H2O2, generating either cysteine sulfenic acid (CSOH) or disulfide (CSSC), is involved in redox homeostasis and signaling. Compared with quantification of the cysteine content, monitoring the cysteine dynamics in real-time, in particular, takes on even greater importance. However, existing fluorescent probes suffer from low specificity or irreversible recognition mechanisms. In the present work, we have successfully developed a reversible fluorescent probe for the cycle between cysteine and H2O2 based on the Michael addition–elimination reaction. This probe features a specific and quantitative response to cysteine. The reversible detection was realized repeatedly with the addition of cysteine and H2O2 in order. We also demonstrated its usage for monitoring exogenous and endogenous cysteine in living cells. Eventually, this probe was capable of imaging cysteine dynamically in real-time.

Purpose Fetal fraction (FF) is the percent of cell-free DNA (cfDNA) in the mother’s peripheral blood that is of fetal origin, which plays a pivotal role in noninvasive prenatal screening (NIPS). We present a method that can reliably estimate FFs by examining autosome single-nucleotide polymorphisms (SNPs). Methods Even at a very low sequencing depth, there are plenty of SNPs covered by more than one read. At those SNPs, we define read heterozygosity and demonstrate that the percent of read heterozygosity is a function of FF, which allows FF to be inferred. Results We first demonstrated the effectiveness of our method in inferring FF. Then we used the inferred FF as an informative alternative prior to computing Bayes factors to test for aneuploidy, and observed better power than the Z-test. In analysis of clinical samples, we were able to identify female–male twins thanks to the accurate FF inference. Conclusion Knowing FF improves efficacy of NIPS. It brings a powerful Bayesian method, allows “no call” for samples with small FFs, renders screening for XXY syndrome simpler, and permits an adaptive design to sequence at a higher depth for samples with small FFs.

Asherman’s syndrome (AS) is an endometrial disorder in which intrauterine adhesions crowd the uterine cavity and wall. The fibrotic adhesions are primarily the result of invasive uterine procedures that usually involve the insertion of surgical equipment into the uterus. This syndrome is accompanied by a number of clinical manifestations, including irregular or painful menstruation and infertility. The most prevalent treatment is hysteroscopy, which involves the physical removal of the fibrous strands. Within the last decade, however, the field has been exploring the use of cell-based therapeutics, in conjunction with biomaterials, to treat AS. This review is a recapitulation of the literature focused on cellular therapies for treating AS.

e21008 Background: Anaplastic lymphoma kinase (ALK) is one of the major oncogenic driver genes in lung cancer, and fusion as the main mutation type, of which EML4 is the most common fusion ligand. With the development of next-generation sequencing (NGS), some other rare fusion ligands and complex fusions have been discovered. The prognosis of patients with EML4-ALK fusion, non EML4-ALK fusion and multiple ALK fusion was different. Methods: We retrospectively analyzed NGS (including tissue, blood, or other body fluid samples) in 61 patients with ALK[+] lung cancer, including 59 patients with NSCLC and 2 patients with SCLC. Grouping was determined according to whether it was EML4-ALK fusion and multiple fusion. Results: In our data, the partner fused to the ALK gene are diverse, including EML4, KIF5B, TSN and others. Among them, EML4 was the most common ligand in ALK[+] NSCLC, accounting for 93.2% (55/59). Among the different fusion sites of EML4-ALK, V1 (E13:A20) and V3 (E6:A20) mutations were the most common, accounting for 45.5% (25/55) and 41.8% (23/55), respectively. Several novel ALK fusion partners were discovered in this study, including MCFD2, LINC01251, MVP17, CREG2, LINCO1498 and so on. In addition, the incidence of intergenic sequence-ALK fusions was 16.4% (10/61), such as ANXA4-ALK(A[intergenic]:A20), CREG2-ALK (C[intergenic]:A20), HCN1-ALK(H[intergenic]:A20), TSN-ALK(T[intergenic]:A20), RSAD2-ALK(R [intergenic]:A20) and so on. 19.0% (12/61) of the patient had multiple fusion, of which only one patient had multiple fusion of EML4-ALK (V2+V5'+V3a/b), and the remaining patients had co-fusion of EML4-ALK and non EML4-ALK (Table). V3 were more likely to coexist with non EML4-ALK fusions than V1 or other variants (P = 0.047). Multiple fusions were more likely to occur with non EML4-ALK fusions (P < 0.000). Compared with EML4-ALK fusion, mPFS treated with crizotinib in non EML4-ALK fusion were significantly shorter (18.2 vs. 8.5 months, P = 0.035). In the context of crizotinib treatment, multiple fusions were associated with worse mPFS compared with single fusions (13.8 vs. 8.4 months, P = 0.008). In addition, For SCLC patients with ALK fusion (n = 2), the PFS of crizotinib treatment were 8.0 and 30.6 months, respectively. Conclusions: Due to the heterogeneity of tumor development resulting in the diversity of ALK fusions, non EML4-ALK fusions and multiple fusions imply a poorer response to crizotinib. ALK gene status prior to ALK-TKI therapy helps predict drug efficacy and patient prognosis.[Table: see text]

e21075 Background: Advanced-stage anaplastic lymphoma kinase fusion-positive (ALK[+]) NSCLC has significantly benefited from ALK-TKI. It is still uncertain which second-generation(2G) ALK-TKI will benefit patients more after crizotinib resistance. Methods: We retrospectively analyzed the treatment history of 104 patients with ALK[+] NSCLC. Grouping was determined according to the type of 2G TKI patients selected after failure of crizotinib, including systemic and intracranial. Results: Overall, the median follow-up time was 24.2 (95%CI: 21.3-27.1) months, and 45(43.2%) eligible patients were alive at the end of follow-up. After Crizotinib treatment failure, 91(87.5%) patients received subsequent therapy (including targeted therapy and chemotherapy), and 90.1% (82/91) of patients received sequential 2G TKI treatment, with overall ORR of 68.3%, mPFS of 13.4 (95%CI:10.0-16.7) months, and mOS of 26.3 (95%CI:11.6-41.1) months. The mOS for Alectinib, Ceritinib, and Brigatinib were 34.5 (95%CI: 14.8-54.3), 19.4 (95%CI: 11.8-27.0) and 43.8 (95%CI: 10.0-77.6) months, respectively. The mPFS of Alectinib, Ceritinib, Brigatinib and Ensartinib were 17.3 (95%CI: 12.9-21.8) months, 13.4 (95%CI: 9.5-17.8) months, 10.7 (95%CI: 6.6-14.9) months and 8.4 (95%CI: 1.3-14.8) months, ORR were 68.6%, 70.8%, 69.2% and 60.0%, respectively (Table.1). For crizotinib resistant patient, 2G TKI showed no significant difference in prolonging PFS (P = 0.599) and OS (P = 0.681). Brain metastases were found in 67.1% (55/82) of crizotinib resistant patients, and mPFS of Alectinib, Ceritinib, Brigatinib and Ensartinib were 22.1 (95%CI:9.6-30.6) months, 12.6 (95%CI:8.3-16.9) months, 21.0 (95%CI:0.5-45.7) months and 14.7 (95%CI:3.8-25.5) months; ORR were 72.4%, 50.0%, 66.7% and 40.0%, respectively (Table.1). In particular, the ORR of Alectinib and Brigatinib was significantly higher than that of Ceritinib and Ensartinib (P < 0.000), while the mPFS of Alectinib was significantly better than Ensartinib (P = 0.029). Conclusions: After crizotinib resistance, nearly 90% of patients choose sequential 2G TKI. There was no significant difference in mPFS and mOS among patients treated with different 2G ALK-TKI. For patients with CNS metastases, treatment with Alectinib and Brigatinib results in higher ORR and PFS.[Table: see text]

To evaluate maternal and fetal outcomes in women with Gitelman syndrome (GS).Retrospective analysis of the clinical data of five patients with the clinical diagnosis of GS during pregnancy, who were admitted to Beijing Shijitan Hospital, Capital Medical University between 2013 and 2019, was conducted.Five women with GS during pregnancy who finally gave birth to a total of eight newborns have been included. Three cases were primiparas and two cases were multiparas. Two cases were diagnosed before pregnancy and three cases were diagnosed in first or second trimester. The primary treatment was oral or intravenous electrolytes supplement. Three patients delivered through the vagina, and shoulder dystocia occurred in one patient. Two patients delivered by cesarean section, with one because of symptom of limb weakness during the course of labor and the other owing to gestational diabetes with fetal macrosomia. Postpartum hemorrhage and urinary retention were not reported in these cases. In perinatal period all the infants had good outcome. The children, aged between six months and five years, were healthy and well-developed during follow-up.The maternal and perinatal outcome is usually favorable. We should pay attention to electrolyte examination in the first trimester in order to diagnose and manage the GS efficiently. Well-controlled patients with Gitelman syndrome can deliver through the vagina.

Cysteine oxidation by H

To address the issues of “shuttle effect” of soluble polysulfides and sluggish redox kinetics in the cathodes of lithium-sulfur batteries, the acceleration of the polysulfides conversion via electrocatalysis is a promising solution. As a common electrocatalyst, the catalytic ability of two dimensional (2D) MoS2 is considerably diminished due to agglomeration of nanosheets and insufficient active sites. In this work, a phosphorus-doped three dimensional (3D) network of MoS2-based interlayer sandwiched between the S cathode and the separator is developed. The 3D network could prevent 2D nanosheets from stacking and provide fast diffusion channels for Li ions transfer. Phosphorus doped MoS2 forms stronger Mo-S and Li-P bonds to anchor polysulfides and to promote cleavage of S-S or Li-S bonds of lithium polysulfides to accelerate the polysulfides conversion. As a result, the cell exhibits a high specific capacity of 884.4 mAh g−1 after 100 cycles at 0.1 C even under the high sulfur loading condition (3.7 mg cm−2). This work may encourage more efforts on heteroatom doping in electrocatalyst to realize a high performance in lithium−sulfur batteries.

Stem cell therapy is one of the promising strategies for the treatment of ischemic heart disease. However, the clinical application of stem cells transplantation is limited by low cell engraftment in the infarcted myocardium. Taking advantage of pretargeting and bioorthogonal chemistry, we engineered a pretargeting and bioorthogonal chemistry (PTBC) system to capture endogenous circulating stem cells and target them to the injured heart for effective repair. Two bioorthogonal antibodies were i.v. administrated with a pretargeting interval (48 h). Through bioorthogonal click reaction, the two antibodies are linked in vivo, engaging endogenous stem cells with circulating platelets. As a result, the platelets redirect the stem cells to the injured heart. In vitro and in vivo studies demonstrated that bioorthogonal click reaction was able to induce the conjugation of platelets and endothelial progenitor cells (EPCs) and enhance the binding of EPCs to collagen and injured blood vessels. More importantly, in a mouse model of acute myocardial infarction, the in vivo results of cardiac function, heart morphometry, and immunohistochemistry assessment all confirmed effective heart repair by the PTBC system.

Enzymes contain several subunits to maintain different biological functions. However, it remains a great challenge for specific discrimination of one subunit over another. Toward this end, the fluorescent probe TPEMA is now presented for highly specific detection of the B subunit of cytosolic creatine (CK) kinase isoenzyme (CK-B). Owing to its aggregation-induced emission property, TPEMA shows highly boosted emission toward CK-B with a fast response time and very low interference from other analytes, including the M subunit of CK (CK-M). With the aid of a Job plot assay, ITC assay and molecular dynamics simulation, it was directly confirmed that the remarkably enhanced fluorescence of TPEMA in the presence of CK-B results from the restriction of single molecular motion in the cavity. Selective wash-free fluorescence imaging of CK-B in macrophages under different treatments was successfully demonstrated.

Stem cell therapies have shown promise in treating acute and chronic ischemic heart disease. However, current therapies are limited by the low retention and poor integration of injected cells in the injured tissue. Taking advantage of the natural infarct-homing ability of platelets, we engineered CD34 antibody-linked platelets (P-CD34) to capture circulating CD34-positive endogenous stem cells and direct them to the injured heart. In vitro, P-CD34 could bind to damaged aortas and capture endogenous stem cells in whole blood. In a mouse model of acute myocardial infarction, P-CD34 accumulated in the injured heart after intravenous administration, leading to a concentration of endogenous CD34 stem cells in the injured heart for effective heart repair. This represents a new technology for endogenous stem cell therapy.

e16547 Background: It is reported that hyperfibrinogenemia is commonly seen in gastric cancer. This study aim to discuss the association between fibrinogen level and preoperative clinicopathological factors and to evaluate the value as a predictor of prognosis. Methods: Retrospectively reviewed the medical records and follow-up data of patients with gastric cancer who underwent curative resection from January 2011 to December 2014 at Surgery Department of the Fourth Hospital of Hebei Medical University. Fibrinogen was measured a week before the surgery. Results: A total of 248 cases were enrolled. The means±SD of fibrinogen was 3.28±1.06g/L. Fibrinogen level was higher in older adults(≥60y), advanced tumor, poorly differentiated, deep invasion, lymph node metastasis, large tumor size and in those with high CEA, platelet count, albumin, NLR and PLR,( P< 0.05). All the people were divided by the TNM staging system and found that the plasma fibrinogen was higher in stageⅡand Ⅲ (stageⅠvs. stageⅡ: 2.84±0.72g/L vs. 3.36±1.18g/L, P= 0.009;stageⅠvs. stage Ⅲ: 2.84±0.72g/L vs. 3.43±1.07g/L, P< 0.001), however, there was no difference between stageⅡand Ⅲ( P= 0.662)(our study did not enrolled stage IV patients).When patients were classified into 4 groups according to the T classification, the plasma fibrinogen level gradually increased with increasing depth of cancer invasion (one way ANOVA; P= 0.002). Yet, when the patients who have lymph nodes metastasis classified according to the N classification, the differences among them did not have statistically significance ( P= 0.333). Multivariate analysis revealed that hyperfibrinogenemia had an independent association with advanced cancer (odds ratio,2.686(1.012-7.125); P= 0.047), lymph node metastasis (odds ratio,2.012 (1.012-3.125); P= 0.035) and tumor size(odds ratio,1.949 (1.099-3.454); P= 0.022). Our study aslo suggested that the patients with hyperfibrinogenemia before surgery showed a significantly lower survival rate (Log-Rank test; P< 0.001), hyperfibrinogenemia was a independent predictor on the overall survival, which could predict worse clinical outcome. Conclusions: Hyperfibrinogenemia may be considered a useful biomarker to predict advanced tumor, lymph node metastasis and large tumor size and can be a good predictor of worse clinical outcome.

In recent years, value for money (VFM) evaluations using the Public Sector Comparator (PSC) method have gradually been adopted by governments worldwide in the field of public investment, and used as decision-making tools for public–private partnership (PPP) projects. However, there has been little research concerned with such emerging decision-making questions with VFM. This paper proposed a quantitative decision-making method of entropy-weighted Pareto front applied in the specific context of Chinese PPPs, with a case study of an Urban Transit Railway (URT) PPP project from Guizhou province. Factor analysis was used to extract the qualitative indicators of VFM evaluation, associate them with the quantitative characteristics of the project, and thus help public sector decision-makers choose the proper quantitative decision variables.

Fetal fraction (FF) is the percent of cell-free DNA (cfDNA) in the mother's peripheral blood that is of fetal origin, which plays a pivotal role in noninvasive prenatal screening (NIPS). We present a method that can reliably estimate FFs by examining autosome single-nucleotide polymorphisms (SNPs).Even at a very low sequencing depth, there are plenty of SNPs covered by more than one read. At those SNPs, we define read heterozygosity and demonstrate that the percent of read heterozygosity is a function of FF, which allows FF to be inferred.We first demonstrated the effectiveness of our method in inferring FF. Then we used the inferred FF as an informative alternative prior to computing Bayes factors to test for aneuploidy, and observed better power than the Z-test. In analysis of clinical samples, we were able to identify female-male twins thanks to the accurate FF inference.Knowing FF improves efficacy of NIPS. It brings a powerful Bayesian method, allows "no call" for samples with small FFs, renders screening for XXY syndrome simpler, and permits an adaptive design to sequence at a higher depth for samples with small FFs.

Stem cell therapies have made strides toward the efficacious treatment of injured endometrium and the prevention of intrauterine adhesions, or Asherman’s syndrome (AS). Despite this progress, they are limited by their risk of tumor formation, low engraftment rates, as well as storage and transportation logistics. While attempts have been made to curb these issues, there remains a need for simple and effective solutions. A growing body of evidence supports the theory that delivering media, conditioned with mesenchymal stem cells, might be a promising alternative to live cell therapy. Mesenchymal stem cell-secretome (MSC-Sec) has a superior safety profile and can be stored without losing its regenerative properties. It is versatile enough to be added to a number of delivery vehicles that improve engraftment and control the release of the therapeutic. Thus, it holds great potential for the treatment of AS. Here, a new strategy for loading crosslinked hyaluronic acid gel (HA gel) with MSC-Sec is reported. The HA gel/MSC-Sec treatment paradigm creates a sustained release system that repairs endometrial injury in rats and promotes viable pregnancy.