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Insulin resistance is the major factor involved in the pathogenesis of type 2 diabetes. Although the oral drug metformin (MH) is widely used to reduce hyperglycemia, it is associated with adverse effects. Therefore, there is an urgent need to search for safe and natural foods that do not cause adverse effects as alternatives to commercial drugs. In this study, the active substances from Spirulina platensis, Grifola frondosa, Panax ginseng, and chromium-rich yeast were used to obtain Spirulina functional formulations (SFFs), and its therapeutic effects on mice with glycolipid metabolism disorder (GLD) were investigated. Results showed that SFFs not only improved glycolipid metabolism and reduced inflammation in mice with GLD but also showed good regenerative effects on the liver, jejunum, and cecum tissues. Moreover, SFFs could inhibit the growth of harmful microbes in the intestine and promote the proliferation of beneficial bacteria, thereby promoting the production of short-chain fatty acids and further regulating GLD. Additionally, SFFs significantly increased the expression of INS, INSR, IRS-1, PI3K, AKT-1, and GLUT-4 genes and significantly decreased that of GSK-3β in the INS/PI3K/GLUT-4 signaling pathway. Therefore, the findings of this study suggest that SFFs can be further developed as a new class of therapeutic agents against GLD.

BACKGROUND: Lymphopenia during definitive radiotherapy (RT) has been shown to reduce survival in patients with cervical cancer. However, there are few studies on the significance of onset time of lymphopenia during RT in patients with cervical cancer. OBJECTIVE: This study aimed to exam the prognostic significance of early onset of severe lymphopenia (EOSL) during definitive RT in patients with cervical cancer. METHODS: Newly diagnosed cervical cancer patients treated with definitive RT from January 2015 to December 2019 were eligible for this retrospective study. EOSL was defined as first onset of grade 3–4 lymphopenia ⩽ 3 weeks from the start of RT. Mean body dose (MBD) was the mean radiation dose absorbed by the body during the whole course of external beam RT (EBRT) and was directly obtained from the dose volume histogram (DVH) of the EBRT planning. Logistic regression analysis and restricted cubic spline (RCS) models were applied to assess relationships between clinicopathological factors and EOSL. Survival analysis was performed using Kaplan-Meier curves and log-rank test. A COX regression model was developed to predict overall survival (OS). RESULTS: A total of 104 patients were included and 59.6% had EOSL. MBD (P= 0.04), concurrent cisplatin (P= 0.011), and pre-RT absolute lymphocyte count (ALC) (P= 0.001) were associated with EOSL. A linear relationship (P for non-linearity = 0.803) between MBD and risk of EOSL was found. Patients with EOSL had decreased OS (2-yr 75.1% vs 91.1%, P= 0.021) and progression-free survival (PFS) (2-yr 71.2% vs 83.7%, P= 0.071). An OS prediction COX model was developed with C-index of 0.835 and AUC of 0.872. CONCLUSIONS: EOSL during definitive RT correlates with MBD and predicts poor survival in patients with cervical cancer.

In most bladder cancer (BC) patients, cancer cells will eventually develop chemical resistance causing increased mortality. This study aimed to explore the mechanism of lncRNA plasmacytoma variant translocation 1 (PVT1) in regulating doxorubicin (ADM) resistance of BC cells. We observed that PVT1 expression was upregulated in ADM-resistant BC cells compared with ADM-sensitive BC cells. Downregulation of PVT1 suppressed ADM-resistant BC cell proliferation and invasion, promoted apoptosis, and increased sensitivity to ADM, while PVT1 overexpression promoted ADM-sensitive BC cell growth and their resistance to ADM. Further study uncovered that PVT1 could interact with and promote mouse double minute 2 (MDM2) expression, and upregulated MDM2-mediated Aurora kinase B (AURKB). Furthermore, Nutlin-3, an inhibitor of MDM2, could counteract the promotive effects of PVT1 overexpression on ADM resistance of ADM-sensitive BC cell, the expression of multidrug-resistance-related proteins, and the inhibition of p53-mediated tumor suppressor genes. And, overexpression of MDM2 or AURKB reversed the promotive effects of PVT1 silence on the ADM sensitivity of ADM-resistant BC cell, and the inhibitory effect on expression multidrug resistance proteins. Mechanically, AURKB increased MDM2-mediated p53 ubiquitination. Taken together, PVT1 promoted BC cell proliferation and drug resistance via elevating MDM2 expression and AURKB-mediated p53 ubiquitination.

Flavonoid compounds such as luteolin exhibit hypolipidemic effects, and there are few reports on the hypoglycemic activity of luteolin derivatives. In this research, 6,8-(1,3-diaminoguanidine) luteolin (DAGL) and its Cr complex (DAGL·Cr) were obtained as a result of structural modifications to luteolin, and the hypoglycemic activities and the composition of intestinal microbiota in T2DM mice were investigated. This study found that DAGL and DAGL·Cr could significantly restore body weight, FBG, OGTT, AUC, and GSP in T2DM mice. Moreover, the pancreatic islet function index and the biochemical indicators of serum and the liver were also significantly improved. The histopathological results also showed that DAGL and DAGL·Cr had a stronger repair ability in the liver and the pancreas. It was also revealed that the potential hypoglycemic mechanism of DAGL and DAGL·Cr was involved in the simultaneous regulation of PI3K/AKT-1/GSK-3β/GLUT-4 and PI3K/AKT-1/mTOR/S6K1/IRS-1. Furthermore, DAGL and DAGL·Cr could also regulate the structure of the intestinal microbiota and increase the content of SCFA to relieve the symptoms of hyperglycemia in T2DM mice. This included a significant reduction in the ratio of Firmicutes and Bacteroidetes (F/B), and at the genus level, an increase in the relative abundance of

Insulin resistance is the major factor involved in the pathogenesis of type 2 diabetes. Although the oral drug metformin (MH) is widely used to reduce hyperglycemia, it is associated with adverse effects. Therefore, there is an urgent need to search for safe and natural foods that do not cause adverse effects as alternatives to commercial drugs. In this study, the active substances from

Post-dural puncture headache (PDPH), or spinal headache, is the most common serious complication resulting from iatrogenic puncture of the dura during epidural or spinal anesthesia and cerebrospinal fluid (CSF) leak in pregnant women.To analyze the effectiveness and safety of opioids as a prophylaxis approach in treating obstetric patients who underwent unintentional dural puncture during the initiation of neuraxial anesthesia.A systematice review and meta-analysis.No restriction regarding study type.PubMed, Embase, and the Cochrane library were searched for available papers published up to September 2020.According to the eligibility criteria, 10 studies were included with post-dural puncture headache (PDPH) incidence as the primary outcome and the number of epidural blood patch (EBP) required as the second outcome. The risk estimates of each study were reported as odds ratios (ORs). The results showed morphine does not decrease the incidence of PDPH (OR = 0.45, 95% CI: 0.15 - 1.34, P = 0.153, I2 = 74.4%, Pheterogeneity = 0.004) and the use of EBP (OR = 0.40, 95% CI: 0.08 - 1.95, P = 0.259, I2=73.7%, Pheterogeneity = 0.004). Fentanyl does not decrease the incidence of PDPH (OR = 0.35, 95% CI: 0.01-13.77, P = 0.576, I2 = 81.0%, Pheterogeneity = 0.022).The small number of included studies, high heterogeneity, and variety in study designs.Exposure to opioids for any reason after the diagnosis of unintentional dural puncture is not associated with a reduced risk of PDPH and does not decrease the need for therapeutic EBP.

Land resources are not only the spatial carriers of social and economic development, but also the carriers of environmental and ecological services. With the accelerated urbanization, the non-coordinated development of land resources and environmental protection will restrict economic growth and the benefits of land use changes. Moreover, the economic efficiency and environmental efficiency of land use largely depend on the value judgment of the decision makers on the future human environment. Therefore, it is extremely important to achieve a win–win outcome of land development and ecological protection. In this research, a new analysis framework for land use efficiency was proposed from the perspective of decision makers' different benefit preferences. This framework uses the unexpected output of environmental pollution as a bridge to build a two-stage data envelopment analysis (DEA) model to evaluate the economic efficiency, environmental efficiency and overall efficiency of land development, and weight parameters were constructed to express decision-makers' preferences. The model not only considers the objectivity of the scores of land use efficiency, but also guarantees the subjectivity of decision-makers in land use management. This is also the biggest difference between previous studies in this study. The specific conclusions are: (I) as decision makers tend to focus on economic benefits, economic efficiency first rises and then declines. It can be seen that ignoring the problem of environmental pollution will reduce economic efficiency. (II) Generally speaking, the efficiency of compact land development (0.883) in various counties and cities in Taiwan is greater than the efficiency of expanded land development (0.737). This research can provide guidance on the distribution of land resources and the development of land space on a macro-regional scale.

Disinfection by-products (DBPs) are inevitably generated in the process of disinfection. Among them, aromatic halogenated DBPs, such as 2,4,6-trichlorophenol (TCP), 2,4,6-tribromophenol (TBP) and 2,4,6-triiodophenol (TIP), have attracted considerable interest for their high toxicity. A systematic nephrotoxicity evaluation of 2,4,6-trihalophenols is still lacking. In this study, mice were exposed to TCP, TBP and TIP ranging from environmental-related low concentration to high concentration that commonly used in animal study (0.5-200 μg/L). Kidney histopathology, urine protein detection and urine metabolomics were performed. Remarkable changes including kidney damage, proteinuria and glomerular mesangial cell proliferation were observed after three 2,4,6-trihalophenol exposure, even at low concentration of 0.5 μg/L. The nephrotoxicity rank order was TIP TBP TCP. Additionally, in vivo exposure to 2,4,6-trihalophenols also led to apparent changes in urinary metabolic profiles. Biosynthesis pathways of branched-chain amino acids (BCAAs, containing valine, leucine and isoleucine) were disturbed even at the early stage of exposure (4 weeks). Intriguingly, it has been reported that BCAAs could promote the proliferation of glomerular mesangial cells. Thus, in vitro cell experiments were further performed on mouse glomerular mesangial cell line MES-13. Consistently with in vivo results, cell proliferation was observed in MES-13 cells after exposure to 2,4,6-trihalophenols, especially to TBP and TIP. Meanwhile, TCP at high concentration, TBP and TIP at not only high concentration but also low concentration, induced BCAAs accumulation in glomerular mesangial cells, which was completely commensurate to that observed in cell proliferation assay. Then the proliferation of MES-13 cells induced by 2,4,6-trihalophenols was remarkably inhibited after BCAAs interference. Here we provide direct link between disturbed BCAAs and the nephrotoxicity of 2,4,6-trihalophenols. 2,4,6-trihalophenols could induce excess BCAAs, which further led to proliferation of glomerular mesangial cells and renal injury. This study revealed the nephrotoxicity of aromatic trihalogenated DBPs and provided new insights into the potential toxic mechanisms.

With the aggravation of rural aging, the well-being and self-rated health level of older people in rural communities are significantly lower than those in urban communities. Past studies hold that mobility is essential to the quality of life of the elderly, and well-being depends on their own adaptation strategies in the built environment. Therefore, this study combines three key factors related to active aging: environment, health and mobility, and assumes that the elderly with good health status will have environmental proactivity and a wider range of daily mobility in a poor rural built environment. This study attempts to track daily mobility by using a space–time path method in time geography and then to explore the relationship between outdoor mobility and older people’s self-rated health. A 1-week mobility path survey for 20 senior citizens of Xishi Village, a typical rural village in Taiwan, was conducted by wearing a GPS sports watch. A questionnaire survey and in-depth interviews were done to provide more information about the seniors’ personal backgrounds and lifestyles. The results show that when the built environment is unfit to the needs of daily activities, half of the participants can make adjustment strategies to go beyond the neighborhoods defined by administrative units. Correlation analysis demonstrated that mental health is associated with daily moving time and distance. In addition, men have higher self-rated health scores than women, and there are significant statistical differences between married and widowed seniors in daily outing time and distance. This exploratory study suggests that in future research on rural health and active aging in rural areas, understanding the daily outdoor mobility of the elderly can help to assess their health status and living demands and quickly find out whether there is a lack of rural living services or environmental planning.

Halophenolic disinfection byproducts (DBPs) in drinking water have attracted considerable concerns in recent years due to their wide occurrence and high toxicity. The liver has been demonstrated as a major target organ for several halophenolic DBPs. However, little is known about the underlying mechanisms of liver damage caused by halophenolic DBPs. In this study, 2,4,6-trichlorophenol (TCP), 2,4,6-tribromophenol (TBP) and 2,4,6-triiodiophenol (TIP) were selected as representative halophenolic DBPs and exposed to C57BL/6 mice at an environmentally-relevant concentration (0.5 μg/L) and two toxicological concentrations (10 and 200 μg/L) for 12 weeks. Then, a combination of histopathologic and biochemical examination, liver transcriptome, serum metabolome, and gut microbiome was adopted. It was found that trihalophenol exposure significantly elevated the serum levels of alkaline phosphatase and albumin. Liver inflammation was observed at toxicological concentrations in the histopathological examination. Transcriptome results showed that the three trihalophenols could impact immune-related pathways at 0.5 μg/L, which further contributed to the disturbance of pathways in infectious diseases and cancers. Notably, TBP and TIP had higher immunosuppressive effects than TCP, which might lead to uncontrolled infection and cancer. In terms of serum metabolic profiles, energy metabolism pathway of citrate cycle and amino acid metabolism pathways of valine, leucine, and isoleucine were also significantly affected. Integration of the metabolomic and transcriptomic data suggested that a 12-week trihalophenol exposure could prominently disturb the glutathione metabolism pathway, indicating the impaired antioxidation and detoxification abilities in liver. Moreover, the disorder of the intestinal flora could interfere with immune regulation and host metabolism. This study reveals the toxic effects of halophenolic DBPs on mammalian liver and provides novel insights into the underlying mechanisms of hepatotoxicity.

Background and purpose: To introduce a standard linac with true attachment free, rapid arc and dose-drop scheme for positioning related dose deviation control based total body irradiation(TBI).Materials/Methods: One eight years old girl diagnosed with acute lymphocytic leukemia underwent TBI in 2020. Target volumes and organs at risk were contoured after CT simulation. Total sixteen ARC and four AP-PA from five isocenters were designed. A dose-drop scheme on both sides of adjacent region were performed to reduce positioning-related dose deviation. A series of quality assurance before radiotherapy and real-time dose monitoring during radiotherapy were carried out.Results: The average on board imaging (OBI) time of per fraction was 40.3 min, the average beam on time of per fraction was 37.2 min, the average time to change from head first to feet first position was 18.4 min. The average mean lung dose was 9.89 Gy, the maximum lens dose was 7.60 Gy, the mean PTV_total dose was 12.17Gy, 98.23% PTV_total volume was covered by 90% of the prescription dose. The maximum dose (Dmax) of PTV_total was 13.65Gy. Dmean and V10.8 of PTV_total are only slightly different(0.49% - 1.89% and 0.26% - 1.04% respectively) even with an error of 5 - 20mm longitudinal misalignments. Gamma passing rate(3mm/ 3% Gamma criteria) are between 93.5% and 100%. Real-time dose monitoring showed an overall deviation of -3.9%±5.51%.Conclusions: Standard linac, rapid arc and dose-drop for positioning-related dose deviation control based total body irradiation is feasible, accurate, and reliable. It is worthy of clinical application.

An extensive study of the electrochemical and spectroelectrochemical properties of 14 boron subphthalocyanine (BsubPc) derivatives with various axial and peripheral substituents was performed in 1,2-dichloromethane (CH2Cl2) containing 0.1 M tetra-n-butyl-ammonium perchlorate (TBAP) as the supporting electrolyte. From the cyclic voltammetry results, all compounds exhibit one oxidation and at least two reduction processes within the solvent potential window of +1.6 to −1.8 V vs SCE. It was found that the reversibility of the redox reactions depends on the axial and peripheral substituents and the dipole moment of the boron-to-axial substituent. In general, UV–vis absorption spectra of the singly reduced BsubPc derivatives exhibit three equal intensity peaks in the 450 to 650 nm region that are derived from the maximum BsubPc absorbance peak upon reduction. Axial substituents affect the intensity of the three peaks upon reduction, while peripheral substituents shift the position of the peaks to higher wavele...

International audience; A series of bis(pyridine)cobalt corroles with one or three nitrophenyl groups on the meso positions of the corrole macrocycle were synthesized and characterized as to their electrochemical and spectroscopic properties in dichloromethane, benzonitrile, and pyridine. The potentials for each electrode reaction were measured by cyclic voltammetry and the electron-transfer mechanisms evaluated by analysis of the electrochemical data combined with UV-visible spectra of the neutral, electroreduced, and electroxidized forms of the corroles. The proposed electronic configurations of the initial compounds and the prevailing redox reactions involving the electroactive central cobalt ion, the electroactive conjugated macrocycle, and the electroactive meso-nitrophenyl groups are all discussed in terms of solvent binding and the number of the nitrophenyl groups and other substituents on the meso-nitrophenyl rings of the compounds.

Four mono-DMSO ligated cobalt corroles with one or three meso-nitrophenyl substituents on the macrocycle were synthesized and investigated as to their electrochemical and spectroscopic properties in CH2Cl2 and DMSO. Comparisons are made between redox reactions of the five-coordinate DMSO adducts in the current study and earlier examined five- and six-coordinate cobalt corroles with pyridine axial ligands which were characterized in a variety of nonaqueous electrochemical solvents. The binding of carbon monoxide (CO) is also investigated.

A series of zinc[Formula: see text]-hydroxylphenylporphyrins was synthesized and characterized by spectroscopic and electrochemical methods in four different nonaqueous solvents. The investigated compounds are represented as [([Formula: see text]-HOPh)[Formula: see text](ptBuPh)[Formula: see text]P]Zn, where P represents the dianion of a porphyrin, Ph represents a phenyl group, HO and [Formula: see text]Bu are para substituents on the meso-phenyl rings of the macrocycle and [Formula: see text] = 0–4. The four utilized nonaqueous solvents were dichloromethane (CH[Formula: see text]Cl[Formula: see text], NN-dimethylformamide (DMF), dimethylsulfoxide (DMSO) and pyridine (Py) which were selected on the basis of their coordinating capabilities. The UV-visible spectra and redox potentials of each porphyrin were analyzed both as a function of Hammett substituent constants for groups at the para-positions of the meso-phenyl rings and as a function of the Gutmann solvent donor number which is related to the coordinating ability of the solvent. Each porphyrin exhibits two reductions in CH[Formula: see text]Cl[Formula: see text], DMSO and Py while three reductions are observed in DMF, the additional reaction being due to a phlorin product generated in solution after formation of the porphyrin dianion. Two or three reversible oxidations were seen in CH[Formula: see text]Cl[Formula: see text], the exact number depending upon the specific porphyrin and the presence of [Formula: see text]-OH substituents at the meso-phenyl rings of the compound. The first two oxidations were assigned as involving the conjugated macrocycle and the third is associated with oxidation of the meso-HOPh group(s).

In this paper, we present a smoothing Newton method for solving the monotone weighted complementarity problem (WCP). In each iteration of our method, the iterative direction is achieved by solving a system of linear equations and the iterative step length is achieved by adopting a line search. A feature of the line search criteria used in this paper is that monotone and nonmonotone line search are mixed used. The proposed method is new even when the WCP reduces to the standard complementarity problem. Particularly, the proposed method is proved to possess the global convergence under a weak assumption. The preliminary experimental results show the effectiveness and robustness of the proposed method for solving the concerned WCP.

Background Pernicious placenta previa (PPP) is the main cause of severe obstetric postpartum hemorrhage (PPH) and hysterectomy and often requires donor blood transfusion. Prophylactic internal iliac artery (IIA) balloon occlusion (BO) combined with cell salvage is increasingly being deployed in parallel transverse uterine incision (PTUI) cesarean section (CS). The aim of this study was to explore the differences in blood management in PTUI CS with or without prophylactic IIA BO and to evaluate the safety and efficacy of cell salvage to reduce the need for donor blood transfusion during PTUI CS. Methods This retrospective study included all women who were diagnosed with PPP and PA and underwent PTUI CS from October 1, 2016, to October 31, 2018. Sixty-four patients were included: 34 underwent prophylactic IIA BO (IIA group), while 30 were treated without prophylactic IIA BO (control group). The primary outcome was a composite measure of perioperative blood management outcomes, including the estimated blood loss (EBL), donor blood transfusion, salvaged blood returned, fresh frozen plasma (FFP), pre- and postoperative serum hemoglobin(Hb) and hematocrit (HCT). In addition, the baseline conditions of mother and neonates were compared. Results The EBL was significantly higher in the IIA group compared to the control group (2883.5 ML in the IIA group versus 1868.7 ML in the control group, P=0.001). Overall, the donor blood transfusion rate was 23.5% (8/34), averaging 4.2 U, in the IIA group versus 30% (9/30), averaging 3.4 U, in the control group, which were not significantly different. The FFP transfusion rate was 47%, averaging 765.6 ml, in the IIA group versus 20%, averaging 816.7 ml, in the control group. In the IIA group, 97.1% used cell savage and had salvaged blood returned, averaging 954.9 ml. In the control group, 90% had salvaged blood returned, averaging 617.9 ml. No cases of amniotic fluid embolism were observed with leukocyte depletion filters. Conclusion Prophylactic IIA BO during PTUI CS in women with PPP and PA does not lead to a statistically significant reduction in EBL. Cell salvage was associated with a reduction in the rate of donor blood transfusion during PTUI CS.

Rationale: Pernicious placenta accrete (PPP) is an obstetrical complication associated with severe life-threatening hemorrhage, which is one of the leading causes of maternal mortality worldwide. Caesarean hysterectomy is the effective method to control intraoperative bleeding for this unscheduled high-risk patient. But a challenge for clinicians in this case is to determine the optimal timing of hysterectomy, because it will directly determine maternal outcome. Patient concerns: We here report a case diagnosed with PPP who suffered from a severe life-threatening hemorrhage during cesarean section but was successfully resuscitated and subsequently discharged from hospital after a smooth recovery. Diagnoses: Although binding the lower uterine segment with a tourniquet markedly reduced bleeding in the surgical field after delivery, massive concealed vaginal life-threatening bleeding occurred immediately, and the amount of vaginal blood loss within 10 minutes was as much as 3000 mL. Interventions: An experienced multidisciplinary team was immediately established, and an unscheduled caesarean hysterectomy was performed immediately, and cell salvage was used. Outcome: The patient was successfully resuscitated and both the parturient and neonate were well and discharged. Lesson: If binding the lower uterine segment with a tourniquet markedly reduces bleeding in the surgical field after cesarean delivery in high-risk patients with PPP, and persistence of hypotension after active resuscitation of the circulation is detected, anesthesiologist should be vigilant enough to detect the possibility of concealed vaginal life-threatening bleeding. If this is confirmed, it should be quickly identified whether bleeding can be quickly controlled within a short period of time. If not, the preferred strategy is that the earlier the unscheduled hysterectomy, the better the outcome. A well-established multidisciplinary team and autologous blood recovery and transfusion techniques are also important in ensuring successful resuscitation of patients.

Background: Maternal cardiac arrest during cesarean section (CS) is an extremely rare but devastating complication. Preventing emergency events from developing into maternal cardiac arrest is one of the most challenging clinical scenarios. Case presentation: A 35-year-old pregnant woman with subvalvular aortic stenosis (SAS) who was scheduled for elective CS under epidural anesthesia, and experienced devastating supine hypotensive syndrome, but was successfully resuscitated after delivery. Conclusions: The performance of tilt position strictly or high-quality continue manual left uterine displacement (LUD) should be performed until the fetus is delivered, otherwise timely delivery of the fetus may be the best way to optimize the deadly condition. Keywords: Subvalvular aortic stenosis, Pregnancy, Cesarean section, Hypotension.

The linear complementarity problem (LCP) has wide applications in economic equilibrium, operations research, and so on, which attracted a lot of interest of experts. Finding the sparsest solution to the LCP has real applications in the field of portfolio selection and bimatrix game. Motivated by the approach developed in compressive sensing, we may try to solve an l1-minimization problem to obtain the sparsest solution to the LCP, where an important theoretical problem is to investigate uniqueness of the solution to the concerned l1-minimization problem. In this paper, we investigate the problem of finding the minimal l1-norm solution to the monotone LCP and propose a sufficient and necessary condition for the uniqueness of the minimal l1-norm solution to the monotone LCP, which provides an important theoretical basis for finding the sparsest solution to the monotone LCP via solving the corresponding l1-minimization problem. Furthermore, several examples are given to confirm our theoretical finding.

Background and purpose To develop and evaluate a fully automatic rectal planning optimizer (ARPO) for volumetric modulated arc therapy (VMAT) treatment planning without human interaction. Materials and methods The ARPO was developed using inherent Pinnacle 3 script language; it was designed to perform the whole planning process including planning structure generation, beam placement, doseline setting and treatment planning. The automatic scheme adjusts the objectives of the objective function simulating the operation of dosimetrists based on our clinical experience. A total of 29 planned rectal cancer patients were retrospectively replanned using the ARPO (VMAT auto ) under the same constraints. Results With the ARPO, the hands-on time required for the whole planning process was significantly reduced to auto plans were recognized as clinically acceptable and 69% as clinically improved; 3% of VMAT auto plans were marked equal and 28% inferior to manually generated VMAT man plans when reviewed in a single-blind study by one experienced radiation oncologist. Without any planning workload the VMAT auto plans had similar planning target volume dose coverage to the VMAT man plans and statistically better organ-at-risk sparing, especially regarding lower small intestine irradiation. Conclusions The ARPO is robust and dramatically efficient in clinical application and provides improved planning quality.

The weighted complementarity problem is an extension of the standard finite dimensional complementarity problem. It is well known that the smoothing-type algorithm is a powerful tool of solving the standard complementarity problem. In this paper, we propose a smoothing-type algorithm for solving the weighted complementarity problem with a monotone function, which needs only to solve one linear system of equations and performs one line search at each iteration. We show that the proposed method is globally convergent under the assumption that the problem is solvable. The preliminary numerical results indicate that the proposed method is effective and robust for solving the monotone weighted complementarity problem.

Pernicious placenta previa (PPP) is the main cause of severe obstetric postpartum hemorrhage and hysterectomy and often requires donor blood transfusion. Prophylactic internal iliac artery (IIA) balloon occlusion (BO) combined with cell salvage is increasingly being deployed in parallel transverse uterine incision (PTUI) cesarean section (CS). The aim of this study was to explore the differences in blood management in PTUI CS with or without prophylactic IIA BO and to evaluate the safety and efficacy of cell salvage to reduce the need for donor blood transfusion during PTUI CS.This retrospective study included all women who were diagnosed with PPP and PA and underwent PTUI CS from October 1, 2016, to October 31, 2018. Sixty-four patients were included: 34 underwent prophylactic IIA BO (IIA group), whereas 30 were treated without prophylactic IIA BO (control group). The primary outcome was a composite measure of perioperative blood management outcomes, including the estimated blood loss (EBL), donor blood transfusion, salvaged blood returned, fresh frozen plasma (FFP), pre- and postoperative serum hemoglobin and hematocrit. In addition, the baseline conditions of mother and neonates were compared.EBL was significantly higher in the IIA group compared to the control group (2883.5 mL in the IIA group vs 1868.7 mL in the control group, P = .001). Overall, the donor blood transfusion rate was 23.5% (8/34), averaging 4.2 U, in the IIA group versus 30% (9/30), averaging 3.4 U, in the control group, which were not significantly different. The FFP transfusion rate was 47%, averaging 765.6 mL, in the IIA group versus 20%, averaging 816.7 mL, in the control group. In the IIA group, 97.1% used cell savage and had salvaged blood returned, averaging 954.9 mL. In the control group, 90% had salvaged blood returned, averaging 617.9 mL. No cases of amniotic fluid embolism were observed with leukocyte depletion filters.Prophylactic IIA BO during PTUI CS in women with PPP and PA does not lead to a statistically significant reduction in EBL. Cell salvage was associated with a reduction in the rate of donor blood transfusion during PTUI CS.

Rationale The most common critical incidents in pediatric anesthesia are perioperative respiratory adverse events (PRAE), which occur more often in neonates and account for one-third of anaesthesia-related cardiac arrests. It is crucial to maintain an open stable airway during anesthesia in neonates, as this population has a low oxygen reserve, small airways, and the loss of protective airway reflexes under general anesthesia. Patient concerns A 6-day-old premature newborn underwent minimally invasive sclerotherapy under general anesthesia. For high-risk premature neonates, the selections of the anesthesia and airway device are extremely important, as those factors directly affect the prognosis. Diagnoses B ultrasound and computed tomography (CT) revealed a large mass from the left chest wall to axilla, which was suspected to be a lymphocele. Interventions Minimally invasive sclerotherapy was performed under inhalation anesthesia. After the initiation of anesthesia, a laryngeal mask was placed to control airway. Anesthesia was maintained intraoperatively via sevoflurane inhalation with spontaneous breathing. No accidental displacements or PRAE occurred. Outcome The operation and anesthesia process was stable and safe. The patient discharged at 2 days postoperatively. Lessons Minimally invasive sclerotherapy in a premature neonate is an operation with an extremely short operation time and minimal trauma, but a very high anesthesia risk and risk of PRAE. Anesthesia management is very important in a premature neonate undergoing a very short surgery under general anesthesia. Total sevoflurane inhalation general anesthesia and laryngeal mask airway control with spontaneous breathing may be an ideal option to reduce PRAE during very short surgery in a premature neonate.

International audience; Three series of porphyrins containing a Zn(II) central metal ion and zero, one or two phosphoryl groups at the meso-positions of the macrocycle were characterized as to their electrochemical, spectroscopic and structural properties in non-aqueous media. The investigated compounds are represented as 5,15-bis(4'-R-phenyl)porphyrinatozinc, 10-(diethoxyphosphoryl)-5,15-bis(4'-R-phenyl)porphyrinatozinc and 5,15-bis(diethoxyphosphoryl)-10,20-bis(4'-R-phenyl)porphyrinatozinc, where R = OMe, Me, H or CN. Linear-free energy relationships are observed between the measured redox potentials at room temperature and the electronic nature of the substituents at the 5 and 15 meso-phenyl groups of the macrocycle. The mono-and bis-phosphoryl derivatives with two p-CNPh substituents provide electrochemical evidence for aggregation at low temperature, a greater degree of aggregation being observed in the case of 5,15-bis(diethoxyphosphoryl)-10,20-bis(4'-CN-phenyl)porphyrinatozinc(II). This compound was characterized in further detail by variable temperature 1 H and 31 P{1H} NMR spectroscopy in solution combined with single crystal X-ray analysis in the solid state. The data obtained from these measurements indicating that this porphyrin has a dimeric structure in CDCl3 at 223-323 K but forms a 2D polymeric network when it is crystalized from a CHCl3/MeOH mixture.

BACKGROUND Protocadherin 8 (PCDH8) functions as a tumor-suppressor gene in many types of cancer. This study aimed to investigate the role of PCDH8 in esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS Cell proliferation, apoptosis, transwell assay, tube formation assays, and tumor xenograft experiment were performed to explore the role of PCDH8 in the progression of ESCC. RESULTS PCDH8 was found to be downregulated in ESCC cells. Ectopic expression of PCDH8 blocked proliferation, invasion, and migration and induced apoptosis in ESCC cells. Furthermore, vascular endothelial growth factor A (VEGFA) secretion and the AKT signaling pathway were also inhibited when PCDH8 was upregulated. PCDH8 overexpression suppressed epithelial-mesenchymal transition (EMT) and pro-angiogenic activity of ESCC cells. In a mouse model of ESCC xenograft tumors, PCDH8 overexpression remarkably restrained tumor cell growth, with the tumor inhibition rate of 75.2%. PCDH8 was the target of miR-200c and had a negative correlation with miR-200c. CONCLUSIONS PCDH8 exerts a tumor-suppressive effect against ESCC cells. However, further studies are required to elucidate the exact molecular mechanism underlying the antitumor activity of PCDH8 in ESCC.

Hypoxic‑ischemic encephalopathy is one of the most notable causes of brain injury in newborns. Cerebral ischemia and reperfusion lead to neuronal damage and neurological disability. In vitro and in vivo analyses have indicated that E3 ubiquitin protein ligase (Huwe1) is important for the process of neurogenesis during brain development; however, the exact biological function and the underlying mechanism of Huwe1 remain controversial. In the present study, neural progenitor cells, L2.3, of which we previously generated from rat E14.5 cortex, were used to investigate the role of Huwe1 and its effects on the downstream N‑Myc‑Delta‑like 3‑Notch1 signaling pathway during oxygen‑glucose deprivation (OGD). To evaluate the role of Huwe1 in L2.3 cells, transduction, cell viability, lactate dehydrogenase, 5‑bromo‑2'deoxyurine incorporation, western blotting and immunocytochemical assays were performed. The results of the present study indicated that Huwe1 rescued L2.3 cells from OGD‑induced insults by inhibiting proliferation and inducing neuronal differentiation. In addition, Huwe1 was suggested to mediate the survival of L2.3 cells by inhibiting the activation of the N‑Myc‑Notch1 signaling pathway. Of note, the effects of Huwe1 on Notch1 signaling were completely abolished by knockdown of N‑Myc, indicating that Huwe1 may require N‑Myc to suppress the activation of the Notch1 signaling in L2.3 cells. The determination of the neuroprotective function of the Huwe1‑N‑Myc‑Notch1 axis may provide insight into novel potential therapeutic targets for the treatment of ischemic stroke.

Introduction: Splenic ectopic pregnancy (SEP), a special abdominal pregnancy, is extremely rare but carries a high risk of potentially uncontrollable, life-threatening intraperitoneal bleeding at early gestation, which is equivalent to the spontaneous rupture of the spleen. Therefore, early diagnosis of SEP is crucial and may avoid life-threatening situation. Case presentation: A 29-year-old G3P2 woman presented with 50 days of amenorrhea and positive serum β-human gonadotropin (β-HCG) was enrolled into the hospital due to the absence of gestational sac located in the uterine cavity. A pan-abdominal ultrasound scan revealed a 2.6 cm ×1.6 cm hyperechoic mass inferior to the spleen with color Doppler signal surrounding and 0.9 cm anechoic inside. The gynecologist found the gestational sac was located in the dorsal pole of the spleen through the exploratory laparoscopy. Total splenectomy was performed uneventfully to avoid the hemorrhage shock. The patient discharged with no complications and normal 1-month follow-up. Conclusion: It highlights that fully understanding of the knowledge about abdominal pregnancy, especially splenic pregnancy, and early imaging study with ultrasonography could reduce or avoid the misdiagnosis and miss-diagnosis of SEP.

A series of β-functionalized trans-A2B2 tetrabenzoporphyrins have been successfully designed and synthesized through newly developed regioselective bromination chemistry of porphyrins and a Pd(0) catalyzed three-step-one pot reaction. These benzoporphyrins exhibit unique patterns of UV-Vis absorptions and emissions.

Herein the synthesis, spectroscopic characterization, two-photon absorption and electrochemical properties of 3,6-disubstituted carbazole tweezers is reported. A dimer resulting from a Glaser homocoupling was isolated during a Sonogashira coupling reaction between a diethynyl-carbazole spacer and a 5-bromo-triarylporphyrin and the properties of this original compound were compared with the 3,6-disubstituted carbazole bisporphyrin tweezers. The dyads reported herein present a two-photon absorption maximum at 920 nm with two-photon absorption cross-section in the 1200 GM range. Despite a strong linear absorption in the Soret region and moderate fluorescence quantum yield, they both lead to a high brightness reaching 30 000 M(-1) cm(-1) .

Hepatocellular carcinoma (HCC) is one of the most common malignancy tumors with insidious onset, rapid development and metastasis, and poor prognosis. Therefore, it is necessary to understand molecular mechanisms of HCC and identify clinically useful biomarkers for it. This study aimed to investigate the role of retinoblastoma binding protein 5 (RBBP5) in HCC. The expression level of RBBP5 was examined by immunohistochemistry and western blot. The effect of RBBP5 on cell cycle, proliferation, apoptosis, and drug sensitivity was analyzed. RBBP5 was significantly upregulated in HCC tissues and cells. High RBBP5 expression was significantly associated with elevated level of AFP, advanced TNM stage, high Ki-67 expression, larger tumor size, and poor prognosis. Knockdown of RBBP5 significantly inhibited proliferation of HCC cells through cell cycle arrest. In addition, inhibition of RBBP5 increased the sensitivity of HCC cells to doxorubicin. In conclusion, our findings suggest that RBBP5 plays an important role in the progression of HCC and may serve as a novel biomarker and potential therapeutic target for HCC.

The synthesis of unsymmetrical push–pull benzoporphyrins has been realized. UV-Vis and fluorescence spectroscopy, cyclic voltammetry and DFT calculations reveal subtle substituent effects on the electronic and optical properties of these porphyrins.

Background Radiation pneumonitis (RP) is a common side reaction in radiotherapy for esophageal cancer. There are few reports about RP in esophageal cancer patients receiving postoperative intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). This study aims to analyze clinical or dosimetric factors associated with RP, and provides data for radiotherapy planning. Methods We reviewed 68 postoperative esophageal cancer patients who were treated with radiotherapy at the West China Hospital from October 2010 to November 2012 to identify any correlation between the clinical or dosimetric parameters and acute radiation pneumonitis (ARP) or severe acute radiation pneumonitis (SARP) by t-test, chi-square test, and logistic regression analysis. Results Of the 68 patients, 33 patients (48.5%) developed ARP, 13 of which (19.1%) developed SARP. Of these 33 patients, 8 (11.8%), 12 (17.6%), 11 (16.2%), and 2 (2.9%) patients were grade 1, 2, 3, and 4 ARP, respectively. Univariate analysis showed that lung infection during radiotherapy, use of VMAT, mean lung dose (MLD), and dosimetric parameters (e.g. V20, V30) are significantly correlated with RP. Multivariate analysis found that lung infection during radiotherapy, MLD ≥ 12 Gy, and V30 ≥ 13% are significantly correlated with an increased risk of RP. Conclusion Lung infection during radiotherapy and low radiation dose volume distribution were predictive factors associated with RP and should be accounted for during radiation planning.