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Aim: To investigate the efficacy and safety of combining Recombinant Human Endostatin Injection (marketed as Endo) with anti-PD-1 in elderly patients aged 80 and above with non-small cell lung cancer (NSCLC). Methods: Retrospective analysis of 181 patients with NSCLC aged 80 and above treated in the Department of Respiratory and Critical Care Medicine at Chaohu Hospital, affiliated with Anhui Medical University, from June 2019 to January 2024. Patients who received at least one cycle of combined Endo with anti-PD-1 were included based on inclusion criteria. Clinical and pathological data were collected, including complete blood count, liver and kidney function, electrocardiogram, coagulation function, thyroid function, cardiac enzymes, and whole-body imaging. Adverse events were recorded with a final follow-up on January 25, 2024. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with safety as a secondary endpoint. Results: This study involved 14 elderly patients with NSCLC aged over 80. Median progression-free survival (mPFS) was 102 days, and median overall survival (mOS) was 311 days. Subgroup analyses based on treatment cycles showed a nonsignificant 441-day mPFS increase in the long-term group (≥6 cycles, 5 patients) compared to the short-term group (<6 cycles, 9 patients). However, the mOS in the long-term group significantly exceeded the short-term group by 141 days, with statistical significance (P=0.048). Further categorization revealed a 204-day shorter mPFS in the monotherapy maintenance group (Endo or Immunol) compared to the combination maintenance group (Endo combined with Immunol, 441 days). The mOS of the monotherapy maintenance group was longer (686 days) than the combination maintenance group (311 days), but no statistical significance (P= 0.710, 0.920). Throughout the treatment, 77 adverse events were recorded, mainly grade 1–2, with no new treatment-related reactions occurred. Overall, the safety of Endo combined with anti-PD-1 was considered good and manageable Conclusion: The combination of Endo and anti-PD-1 could be an effective treatment choice for patients with NSCLC aged 80 and above. [ABSTRACT FROM AUTHOR]

We have investigated (E)-3-thiophene-2-ylindoline-2-one (I) and compared its structural, thermodynamic and kinetic parameters in adsorption as intermolecular hetero-Diels–Alder cycloaddition with C20 to give (E)-3-thiophene-2-ylindoline-2-one[20]fullerene adduct (Ia), in various surroundings, using density functional theory (DFT). By optimisation from the gas phase to C6H6, C2H4Cl2, EtOH, MeNO2, DMSO and H2O, interesting results are obtained: (1) symmetry is protected. (2) the stability and polarity of solute depend on the dielectric constant and polarity of the studied surrounding, on dipolar interaction along with the hydrogen bonding. (3) Generally, the endo-isomer appears thermodynamically more stable than the exo one and we found the formation of a more stable exo-isomer as a result of π-stacking among the Kekulé compound (I) and C20 in endo-isomer. (4) Lack of the repulsion-type interaction at exo-isomer is responsible for stereoselectivity in the adsorption process. (5) The chance of [4 + 2] reaction is ruled out because of the lowest activation energy of 3.7 kcal / mol for the exo transition state (TS) in the gas phase, while the highest activation energy of 7.2 kcal / mol is for endo one in water. (6) We hope adsorption of unstable C20 fullerene similar to stable C60, with biologically active α,β-unsaturated indoline-2-one can be carried out thermally under normal conditions for stereoselective production. [ABSTRACT FROM AUTHOR]

Here, we describe the synthetic improvements to the known compound exo‐dicyclopentadiene‐1‐one (exo‐DCPD‐1‐one). Also, an alternative and efficient synthetic approach to exo‐DCPD‐1‐one was developed in a non‐hazardous manner. All the synthesized compounds here are well‐characterized by NMR analysis. The structure and relative stereochemistry of some key intermediates were confirmed by single‐crystal X‐ray diffraction (XRD) studies. Overall, the synthetic studies described here are useful to prepare exo‐DCPD‐1‐one on a multi‐gram scale in a safe manner. The exo‐DCPD‐1‐one is found to be a useful building block to prepare a wide variety of cyclopentanoids. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Physical Education (20736452) is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: To investigate the efficacy and safety of combining Recombinant Human Endostatin Injection (marketed as Endo) with anti-PD-1 in elderly patients aged 80 and above with non-small cell lung cancer (NSCLC)., Methods: Retrospective analysis of 181 patients with NSCLC aged 80 and above treated in the Department of Respiratory and Critical Care Medicine at Chaohu Hospital, affiliated with Anhui Medical University, from June 2019 to January 2024. Patients who received at least one cycle of combined Endo with anti-PD-1 were included based on inclusion criteria. Clinical and pathological data were collected, including complete blood count, liver and kidney function, electrocardiogram, coagulation function, thyroid function, cardiac enzymes, and whole-body imaging. Adverse events were recorded with a final follow-up on January 25, 2024. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with safety as a secondary endpoint., Results: This study involved 14 elderly patients with NSCLC aged over 80. Median progression-free survival (mPFS) was 102 days, and median overall survival (mOS) was 311 days. Subgroup analyses based on treatment cycles showed a non-significant 441-day mPFS increase in the long-term group (≥6 cycles, 5 patients) compared to the short-term group (<6 cycles, 9 patients). However, the mOS in the long-term group significantly exceeded the short-term group by 141 days, with statistical significance ( P =0.048). Further categorization revealed a 204-day shorter mPFS in the monotherapy maintenance group (Endo or Immunol) compared to the combination maintenance group (Endo combined with Immunol, 441 days). The mOS of the monotherapy maintenance group was longer (686 days) than the combination maintenance group (311 days), but no statistical significance ( P = 0.710, 0.920). Throughout the treatment, 77 adverse events were recorded, mainly grade 1-2, with no new treatment-related reactions occurred. Overall, the safety of Endo combined with anti-PD-1 was considered good and manageable., Conclusion: The combination of Endo and anti-PD-1 could be an effective treatment choice for patients with NSCLC aged 80 and above., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xing, Gao, Zhu, Gao and Yan.)

The essay discusses the religious and ethical message of Shusaku Endo's Silence. Briefly focusing fi rst on the plot of the novel, the article proceeds to discuss the moral dilemma that is the core of the novel and asks whether the dilemma is symmetrical or incommensurable. Next, the essay analyzes the dilemma from the point of view of Max Scheler's theory of the tragic. Finally, to highlight Rodrigues's tragic situation, it discusses the notion of the hiddenness of God. [ABSTRACT FROM AUTHOR]

Readings of Endo's Silence usually focus on the pivotal conversations Ferreira and Inoue have with Rodrigues. Too tight a focus, however, diminishes the challenge the novel poses to modern readers; Silence becomes mere personal tragedy, selling short the novel's complex involvement in Buddhist–Christian dialogue. The character called “the interpreter” broadens that challenge. His three major conversations with Rodrigues present the groundwork and summation for a challenge more perennial and more specifically rooted in Endo's milieu than would appear from just those events surrounding the fumie scene. [ABSTRACT FROM AUTHOR]

An efficient route to phthalides is described starting from easily available bis-propargyl ethers. The method involves Garratt–Braverman cyclization of the ethers to phthalans which are then efficiently oxidized to the phthalides by iodoxy benzoic acid (IBX) which has been shown to be a superior reagent in terms of yield and reagent stoichiometry for such a transformation in comparison with more commonly used KMnO 4 /CuSO 4 reagent. [ABSTRACT FROM AUTHOR]

Background: The concept that pore-forming Kir6.2 and regulatory SUR2A subunits form cardiac ATP-sensitive potassium (K(ATP)) channels is challenged by recent reports that SUR1 is predominant in mouse atrial K(ATP) channels.Objective: To assess SUR subunit composition of K(ATP) channels and consequence of K(ATP) activation for action potential duration (APD) in dog hearts.Methods: Patch-clamp techniques were used on isolated dog cardiomyocytes to investigate K(ATP) channel properties. Dynamic current clamp, by injection of a linear K(+) conductance to simulate activation of the native current, was used to study the consequences of K(ATP) activation on APD.Results: Metabolic inhibitor (MI)-activated current was not significantly different from pinacidil (SUR2A-specific)-activated current, and both currents were larger than diazoxide (SUR1-specific)-activated current in both the atrium and the ventricle. Mean K(ATP) conductance (activated by MI) did not differ significantly between chambers, although, within the ventricle, both MI-induced and pinacidil-induced currents tended to decrease from the epicardium to the endocardium. Dynamic current-clamp results indicate that myocytes with longer baseline APDs are more susceptible to injected K(ATP) current, a result reproduced in silico by using a canine action potential model (Hund-Rudy) to simulate epicardial and endocardial myocytes.Conclusions: Even a small fraction of K(ATP) activation significantly shortens APD in a manner that depends on existing heterogeneity in K(ATP) current and APD. [ABSTRACT FROM AUTHOR]

Copyright of Cuadernos del Centro de Estudios de Diseño y Comunicación is the property of Cuadernos del Centro de Estudios de Diseno y Comunicacion and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Slow delayed-rectifier potassium current (IKs) channels, made of the pore-forming KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD) in cardiac myocytes. The consequences of drug-induced KCNQ1 splice alteration remain unknown.Objective: To study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action potentials (APs) in ventricular myocytes.Methods: Canine endocardial, midmyocardial, and epicardial ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were quantified by using the reverse transcriptase-polymerase chain reaction and Western blot. The effect of amiloride-induced changes in the KCNQ1b/total KCNQ1 ratio on AP was measured by using whole-cell patch clamp with and without isoproterenol.Results: With 50 μmol/L of amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increased in midmyocardial myocytes but decreased in endo- and epicardial myocytes. Likewise, changes in splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortened APD and decreased isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects were demonstrated by using human ventricular myocyte model for AP simulations under beta-adrenergic stimulation. Moreover, amiloride reduced the transmural dispersion of repolarization in pseudo-electrocardiogram.Conclusions: Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia. [ABSTRACT FROM AUTHOR]

Abstract: The very air-sensitive η3-allyldicarbonylethoxydithiocarbonate molybdenum(II) compound [Mo(η3-C3H5)(CO)2(S2COEt)(CH3CN)] (1) are accessible by the reaction of [Mo(η3-C3H5)(CO)2(Br)(CH3CN)2] with KS2COEt in methanol at ambient temperature. The rotational behavior of 1 in solution state was detected by variable-temperature 1H NMR spectroscopy. The mechanism can be described as a trigonal twist, in which the rotation of the triangular face formed by the nitrogen ligand and the two sulfur atoms relative to the face formed by the allyl and the two carbonyl groups. The reactions of 1 with piperidine, 1-piperidinecarbodithioate, and bipyridine ligands give the replacement of the acetonitrile complex [Mo(η3-C3H5)(CO)2(S2COEt)(C5H10NH)] (2), 16-electron complex [Mo(η3-C3H5)(CO)2(S2CNC5H10)] (3), and η1-O-ethyldithiocarbonate complex [Mo(η3-C3H5)(CO)2(S2COEt)(bipy)] (4). Treatment of 1 with various diphos ligands form a mixtures of endo- and exo-complexes [Mo(η3-C3H5)(S2COEt)(CO)(diphos)] (diphos: dppm={bis(diphenylphosphino)methane} (endo-, exo- 5); dppe={1,2-bis(diphenylphosphino)ethane} (endo-, exo- 6); dppa={bis(diphenylphosphino)amine} (endo-, exo- 8)) with ratios of 1:5, 1:2, and 4:5 according to the integration of 31P{1H} NMR spectra, respectively. The orientations of endo and exo are defined for the open face of the allyl group and carbonyl group in the same direction in the former and opposite directions in the latter. The activation barriers of interconversion were determined to be 13.9±0.2kcalmol−1 for (1) and 14.6±0.2kcalmol−1 for (2). The X-ray crystal structures of [Mo(η3-C3H5)(CO)2(S2COEt)(CH3CN)] (1b), [Mo(η3-C3H5)(S2COEt)(CO)(dppm)] (exo-5), and [Mo(η3-C3H5)(S2COEt)(CO)(dppa)] (endo-, exo- 8) are employed to elucidate the coordination mode of the dithiocarbonate ligand and the endo-, exo-orientations. One crystallographically independent molecule of 8 is contained in the cell, in which the open face of the allyl group is disordered toward two directions, i.e. endo and exo. In addition, the endo:exo ratio in the solid state is 62:38. [Copyright &y& Elsevier]

Abstract: Nonsurgical retreatment and surgical endodontics are not always viable solutions to endodontic disease. Access for retreatment may be limited by posts. Surgical endodontics may be limited by anatomical features including bone thickness and nerve and sinus proximity. Anatomical limitations and complex restorations may prevent implant placement. Intentional replantation is considered by many as a procedure of last resort when nonsurgical or surgical endodontics is contra-indicated. The treatment described demonstrates intentional replantation as a procedure to be considered when endodontic procedures or a dental implant are not possible. [Copyright &y& Elsevier]

The idea that Japan is a 'shame culture' and that the Japanese have a weak sense of sin has been an influential one, both in Japan and abroad. It has also often influenced attitudes towards Japan's behaviour in World War II. This idea, however, has its roots in the Japanese critique of pre-war ideology after World War II and in the Japanese reception of Ruth Benedict's The Chrysanthemum and the Sword. In various forms, the idea also became an important element of Nihonbunkaron, those theories of Japanese culture which have been so popular in post-war Japan. The same idea was also given a powerful and influential expression in the novels of Endō Shūsaku (1923-96). Earlier Christian theologians in Japan, such as Yoshimitsu Yoshihiko (1904-45), had often seen traditional Japanese culture as closer to Christianity than modern European culture. To such thinkers, Japan's war with Britain and America was in part a war on modernity itself. By contrast, Endōaccepted the post-war belief that Japan was a shame culture, distant from European Christianity. As his career proceeded, however, he came to take a more positive view of the 'weak' Japanese self. In this sense, his work closely parallels the development of Nihonbunkaron itself. Paradoxically, however, Endō's 'Japanese' reinterpretation of Christianity proved highly popular not only in Japan but also abroad, raising the possibility that it was less exclusively Japanese than his work suggested. [ABSTRACT FROM AUTHOR]

An endo-l,3-β-glucanase was purified from malted barley by ion exchange column chromatography. The purified enzyme protein was demonstrated to be free of other proteins by SDS-polyacrylamide gel electrophoresis and had a molecular weight of 32,000. The amino acid composition of the protein was determined and the complete amino acid sequence was constructed from overlapping peptides generated by enzymatic as well as chemical cleavages. The molecule contains 306 amino acids arranged in one peptide chain. The molecular weight calculated from the sequence is 32,286. The sequence of the 1,3-β-glucanase shows approximately 50% positional identity with two other β-glucanases from barley and tobacco, respectively. [ABSTRACT FROM AUTHOR]

Background: In recent years, the incidence of cervical cancer has increased with increasing life pressures and changes in women's social roles, posing a serious threat to women's physical and mental health., Aim: To explore the clinical effect of Endo combined with concurrent radiotherapy and chemotherapy in the treatment of advanced cervical squamous cell carcinoma., Methods: A total of 120 patients admitted to the oncology department of our hospital were selected as the research subjects. They were equally divided into the test group and the control group (60 patients each) with a random number table. The test group was treated with Endo combined with concurrent radiotherapy and chemotherapy, and the control group was treated with concurrent radiotherapy and chemotherapy. We compared the serum thymidine kinase 1 (TK1), human epididymis protein 4 (HE4), vascular endothelial growth factor (VEGF), and squamous cell carcinoma-associated antigen (SCC-Ag) levels, the clinical effects and survival before and after radiotherapy and chemotherapy, the quality score, and the 3-year follow-up outcomes between the two groups., Results: After chemotherapy, the complete remission + partial remission rate was 85.00% in the test group and 68.33% in the control group; the difference was not statistically significant ( P > 0.05). Before chemotherapy, the serum TK1, HE4, VEGF, and SCC-Ag levels of the two groups were not significantly different ( P > 0.05). After chemotherapy, the levels of serum TK1 (1.27 ± 0.40 pmol/L), HE4 (81.4 ± 24.0 pmol/L), VEGF (235.1 ± 38.0 pg/mL), and SCC-Ag (1.76 ± 0.55 ng/mL) were lower than those in the control group [TK1 (1.58 ± 0.51 pmol/L), HE4 (98.0 ± 28.6) pmol/L, VEGF (284.2 ± 54.1 pg/mL), and SCC-Ag (2.34 ± 0.78 ng/mL)]. The difference was statistically significant ( P < 0.05). Before chemotherapy, there were no significant differences in the physical, role, mood, cognition, social and symptom scale scores of the two groups ( P > 0.05). After chemotherapy, the physical, role, mood, cognitive and social scores were higher in the test group than in the control group, and the difference was statistically significant ( P < 0.05). The symptom scale scores of the test group were all lower than those of the control group, and the difference was statistically significant ( P < 0.05). The 3-year progression-free survival (PFS) rate was 43.33% in the test group and 26.67% in the control group; the overall survival (OS) rate was 48.33% in the test group and 33.33% in the control group; the differences were not statistically significant ( P > 0.05). The 3-year PFS time of the test group was 20.0 mo, which was longer than that of the control group (15.0 mo), and the difference was significant ( P < 0.05). The OS time of the test group was 30.0 mo, which was longer than that of the control group (18.0 mo), and the difference was significant ( P < 0.05)., Conclusion: Endo combined with concurrent radiotherapy and chemotherapy for the treatment of advanced cervical squamous cell carcinoma has a positive effect on reducing the level of tumor markers in patients, prolonging the PFS and OS times of patients, and improving the quality of life., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest between them., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

After the introduction of replacement therapy with glucocorticoids and mineralocorticoids in the 1950s, congenital adrenal hyperplasia (CAH) is no longer a life-limiting condition. However, due to the successful introduction of medical steroid hormone replacement, CAH has become a chronic condition, with associated comorbidities and long-term health implications. The aim of treatment is the replacement of mineralocorticoids and glucocorticoids and the normalisation of elevated androgen concentrations. Long-term consequences of the condition and current treatment regimens include unfavourable changes in the cardiovascular risk profile, impaired growth, testicular adrenal rest tumours (TART) in male and subfertility in both male and female patients with CAH. Optimising replacement therapy in patients with CAH remains challenging. On one hand, treatment with supraphysiological doses of glucocorticoids might be required to normalise androgen concentrations and decrease size or presence of TARTs. On the other hand, treatment with supraphysiological doses of glucocorticoids is associated with an increased prevalence of unfavourable cardiovascular and metabolic risk profiles as well as impaired longitudinal growth and gonadal function. Therefore, treatment of children and adults with CAH requires an individualised approach. Careful monitoring for early signs of complications is already warranted during paediatric healthcare provision to prevent and reduce the impact of comorbidities in later life., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)