Retinol-binding protein 4 as a promising serum biomarker for the diagnosis and prognosis of hepatocellular Carcinoma.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is universally poor. Early diagnosis plays a pivotal role in determining the outcome of HCC. METHODS: We employed a comparative proteomics approach to identify potential biomarkers and validated the application of retinol-binding protein 4 (RBP4) as a biomarker for HCC. RBP4 protein expression was examined in liver tissues from 80 HCC patients through immunohistochemical analysis. Serum RBP4 concentrations were measured by ELISA in a cohort comprising 290 HCC patients, matched 202 chronic hepatitis B patients and 269 healthy controls. Survival data were collected from HCC patients. The diagnostic and prognostic values of RBP4 were evaluated using receiver operating curve (ROC) analysis. RESULTS: The validation results demonstrated a significant reduction in RBP4 levels in both liver tissues and serum samples from HCC patients. ROC analysis of the diagnostic value of RBP4 revealed an AUC of 0.879 (95 % CI: 0.854∼0.903) for HCC. When combined with AFP, the AUC increased to 0.919, with a sensitivity of 87.9 % and specificity of 80 %. Survival analysis revealed significantly reduced overall survival time in individuals with low-expression of RBP4 compared to those with high-expression. The joint prognostic model exhibited an AUC of 0.926 (95 % CI: 0.888∼0.964), which was significantly higher than that of AFP alone (AUC=0.809; P <0.0001). CONCLUSIONS: RBP4 shows a great potential as a biomarker with appreciable diagnostic value, complementing the AFP in HCC diagnosis. Additionally, it holds promise as a prognostic biomarker that, when integrated into a combined prognostic model, could greatly improve HCC prognosis efficiency.

Promising natural products targeting protein tyrosine phosphatase SHP2 for cancer therapy.

The development of Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) inhibitors is a hot spot in the research and development of antitumor drugs, which may induce immunomodulatory effects in the tumor microenvironment and participate in anti-tumor immune responses. To date, several SHP2 inhibitors have made remarkable progress and entered clinical trials for the treatment of patients with advanced solid tumors. Multiple compounds derived from natural products have been proved to influence tumor cell proliferation, apoptosis, migration and other cellular functions, modulate cell cycle and immune cell activation by regulating the function of SHP2 and its mutants. However, there is a paucity of information about their diversity, biochemistry, and therapeutic potential of targeting SHP2 in tumors. This review will provide the structure, classification, inhibitory activities, experimental models, and antitumor effects of the natural products. Notably, this review summarizes recent advance in the efficacy and pharmacological mechanism of natural products targeting SHP2 in inhibiting the various signaling pathways that regulate different cancers and thus pave the way for further development of anticancer drugs targeting SHP2.

Tandem autologous hematopoietic stem cell transplantation for patients with multiple myeloma: a systematic review and meta-analysis.

To evaluate whether patients with multiple myeloma (MM) could benefit from tandem autologous hematopoietic stem cell transplantation (auto-HSCT), PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched, and 10 eligible studies were included after data extraction and quality evaluation. Meta-analysis showed that compared to single autologous hematopoietic stem cell transplantation, tandem auto-HSCT does not improve OS, EFS or efficacy in MM patients, and may even lead to higher treatment-related mortality (TRM). MM patients who received autologous tandem allogeneic HSCT did not achieve better response compared to tandem autologous HSCT. In summary, compared to single autologous hematopoietic stem cell transplantation, tandem autologous hematopoietic stem cell transplantation cannot provide survival advantages for MM patients, and MM patients cannot benefit from autologous tandem allogeneic hematopoietic stem cell transplantation.

Genomes of Meniocus linifolius and Tetracme quadricornis reveal the ancestral karyotype and genomic features of core Brassicaceae.

Brassicaceae represents an important plant family from both a scientific and economic perspective. However, genomic features related to the early diversification of this family have not been fully characterized, especially upon the uplift of the Tibetan Plateau, which was followed by increasing aridity in the Asian interior, intensifying monsoons in Eastern Asia, and significantly fluctuating daily temperatures. Here, we reveal the genomic architecture that accompanied early Brassicaceae diversification by analyzing two high-quality chromosome-level genomes for Meniocus linifolius (Arabodae; clade D) and Tetracme quadricornis (Hesperodae; clade E), together with genomes representing all major Brassicaceae clades and the basal Aethionemeae. We reconstructed an ancestral core Brassicaceae karyotype (CBK) containing 9 pseudochromosomes with 65 conserved syntenic genomic blocks and identified 9702 conserved genes in Brassicaceae. We detected pervasive conflicting phylogenomic signals accompanied by widespread ancient hybridization events, which correlate well with the early divergence of core Brassicaceae. We identified a successive Brassicaceae-specific expansion of the class I TREHALOSE-6-PHOSPHATE SYNTHASE 1 (TPS1) gene family, which encodes enzymes with essential regulatory roles in flowering time and embryo development. The TPS1s were mainly randomly amplified, followed by expression divergence. Our results provide fresh insights into historical genomic features coupled with Brassicaceae evolution and offer a potential model for broad-scale studies of adaptive radiation under an ever-changing environment.

Naked-eye sensitive detection of nanoPET by pH-responsive colorimetric method based on dual-enzyme catalysis.

A pH-responsive colorimetric method based on dual-enzyme catalysis for rapid and facile detection and quantification of nanoPET at environment-dependent concentration is proposed. The nanoPET was hydrolyzed by the synergistic catalysis of cutinase and lipase to terephthalic acid which can be sensitive detected using bromocresol purple as the indicator. The color changed from purple to bright yellow as the nanoPET detection concentration increased from 0 mg/mL to 2 mg/mL which can be detected by UV-Vis. This naked-eye method has a high sensitivity for nanoPET detection with the visual detection cutoff of 31.00 µg/mL, and has a good linearity in the range of 0 âˆ¼ 1 mg/mL with LOD of 22.84 µg/mL. The reliability of this method is verified in the detection of nanoPET in lake water and beer samples, with an average recovery of 87.1 %. The as-developed dual-enzyme colorimetric chemosensor holds promising potential as a robust and effective platform for the sensitive detection of nanoPET.

TANGO6 regulates cell proliferation via COPI vesicle-mediated RPB2 nuclear entry.

Coat protein complex I (COPI) vesicles mediate the retrograde transfer of cargo between Golgi cisternae and from the Golgi to the endoplasmic reticulum (ER). However, their roles in the cell cycle and proliferation are unclear. This study shows that TANGO6 associates with COPI vesicles via two transmembrane domains. The TANGO6 N- and C-terminal cytoplasmic fragments capture RNA polymerase II subunit B (RPB) 2 in the cis-Golgi during the G1 phase. COPI-docked TANGO6 carries RPB2 to the ER and then to the nucleus. Functional disruption of TANGO6 hinders the nuclear entry of RPB2, which accumulates in the cytoplasm, causing cell cycle arrest in the G1 phase. The conditional depletion or overexpression of TANGO6 in mouse hematopoietic stem cells results in compromised or expanded hematopoiesis. Our study results demonstrate that COPI vesicle-associated TANGO6 plays a role in the regulation of cell cycle progression by directing the nuclear transfer of RPB2, making it a potential target for promoting or arresting cell expansion.

Configurable SNAP microresonators induced by axial pre-strain-assisted CO2 laser exposure.

Flexible engineering of the complex shapes of the surface nanoscale axial photonics (SNAP) bottle microresonators (SBMs) is challenging for future nanophotonic technology applications. Here, we experimentally propose a powerful approach for the one-step fabrication of SBMs with simultaneous negative and positive radius variations, exhibiting a distinctive "bump-well-bump" profile. It is executed by utilizing two focused and symmetrical CO2 laser beams exposed on the fiber surface for only several hundred milliseconds. The spectral characteristics of different eigenmodes are analyzed, providing deep insights into the complex physical processes during the CO2 laser exposure. The shapes of the SBMs can be flexibly adjusted by the exposure time, laser power, and applied pre-strains. As a proof of this technique, the developed approach enables the efficient production of a bat SBM, ensuring a uniform field amplitude of the bat mode over the length exceeding 120 µm with 7% deviation. Our proposed technique provides a powerful technique for the efficient fabrication of SBMs with predetermined shapes, laying the groundwork for its applications on microscale optical signal processing, quantum computing, and so on.

Nivolumab Plus 5-Azacitidine in Pediatric Relapsed/Refractory Acute Myeloid Leukemia (AML): Phase I/II Trial Results from the Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) Consortium.

Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium. Thirteen patients, median age 13.7 years, were enrolled. Patients had refractory disease with multiple reinduction attempts. Twelve evaluable patients were treated at the recommended phase II dose (established at dose level 1, 3 mg/kg/dose). Four patients (33%) maintained stable disease. This combination was well tolerated, with no dose-limiting toxicities observed. Grade 3-4 adverse events (AEs) were primarily hematological. Febrile neutropenia was the most common AE ≥ grade 3. A trend to improved quality of life was noted. Increases in CD8+ T cells and reductions in CD4+/CD8+ T cells and demethylation were observed. The combination was well tolerated and had an acceptable safety profile in pediatric patients with relapsed/refractory AML. Future studies might explore this combination for the maintenance of remission in children with AML at high risk of relapse.

Spinal infection caused by Aspergillus flavus in a diabetic: a case report and literature review.

Spinal infections, notably those induced by Aspergillus flavus (A. flavus), represent a complex and uncommon clinical challenge. In individuals with diabetes mellitus, the risk is exacerbated due to a compromised immune response and a heightened vulnerability to non-standard pathogens. This case report chronicles the intricate diagnostic and treatment journey of a 59-year-old diabetic patient grappling with a spinal infection attributed to A. flavus. The diagnosis was delayed due to non-specific symptoms and unclear radiological signs. The administration of voriconazole, a targeted antifungal treatment, resulted in a significant clinical and radiological improvement, underscoring its effectiveness in treating such unusual fungal spinal infections; meanwhile, we found that terbinafine hydrochloride also has a similar effect in treating fungal spinal infections. This case underscores the importance of considering fungal causes in spinal infections among diabetic patients and highlights prompt diagnosis and individualized targeted antifungal therapy.

Positive selection and relaxed purifying selection contribute to rapid evolution of male-biased genes in a dioecious flowering plant.

Sex-biased genes offer insights into the evolution of sexual dimorphism. Sex-biased genes, especially those with male bias, show elevated evolutionary rates of protein sequences driven by positive selection and relaxed purifying selection in animals. Although rapid sequence evolution of sex-biased genes and evolutionary forces have been investigated in animals and brown algae, less is known about evolutionary forces in dioecious angiosperms. In this study, we separately compared the expression of sex-biased genes between female and male floral buds and between female and male flowers at anthesis in dioecious Trichosanthes pilosa (Cucurbitaceae). In floral buds, sex-biased gene expression was pervasive, and had significantly different roles in sexual dimorphism such as physiology. We observed higher rates of sequence evolution for male-biased genes in floral buds compared to female-biased and unbiased genes. Male-biased genes under positive selection were mainly associated with functions to abiotic stress and immune responses, suggesting that high evolutionary rates are driven by adaptive evolution. Additionally, relaxed purifying selection may contribute to accelerated evolution in male-biased genes generated by gene duplication. Our findings, for the first time in angiosperms, suggest evident rapid evolution of male-biased genes, advance our understanding of the patterns and forces driving the evolution of sexual dimorphism in dioecious plants.

Undescribed cytotoxic bisabosqual-type meroterpenoids from an endophytic Stachybotryaceae sp. associated with Delphinium yunnanense.

Five undescribed bisabosqual-type meroterpenoids, bisabosquals E (1) and F (2), stachybisbins J-L (4-6), together with two known ones, were isolated from a novel endophytic fungus KMU22001 within the Stachybotryaceae family. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, single-crystal X-ray diffraction and electronic circular dichroism calculations. Compounds 2, 4 and 6 exhibited significant cytotoxicities against five human cancer cell lines with IC50 values ranging from 1.80 ± 0.08 to 17.76 ± 0.97 µM.

Methyl rosmarinate is an allosteric inhibitor of SARS-CoV-2 3 CL protease as a potential candidate against SARS-cov-2 infection.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been ongoing for more than three years and urgently needs to be addressed. Traditional Chinese medicine (TCM) prescriptions have played an important role in the clinical treatment of patients with COVID-19 in China. However, it is difficult to uncover the potential molecular mechanisms of the active ingredients in these TCM prescriptions. In this paper, we developed a new approach by integrating the experimental assay, virtual screening, and the experimental verification, exploring the rapid discovery of active ingredients from TCM prescriptions. To achieve this goal, 4 TCM prescriptions in clinical use for different indications were selected to find the antiviral active ingredients in TCMs. The 3-chymotrypsin-like protease (3CLpro), an important target for fighting COVID-19, was utilized to determine the inhibitory activity of the TCM prescriptions and single herb. It was found that 10 single herbs had better inhibitory activity than other herbs by using a fluorescence resonance energy transfer (FRET) - based enzymatic assay of SARS-CoV-2 3CLpro. The ingredients contained in 10 herbs were thus virtually screened and the predicted active ingredients were experimentally validated. Thus, such a research strategy firstly removed many single herbs with no inhibitory activity against SARS-CoV-2 3CLpro at the very beginning by FRET-based assay, making our subsequent virtual screening more effective. Finally, 4 active components were found to have stronger inhibitory effects on SARS-CoV-2 3CLpro, and their inhibitory mechanism was subsequently investigated. Among of them, methyl rosmarinate as an allosteric inhibitor of SARS-CoV-2 3CLpro was confirmed and its ability to inhibit viral replication was demonstrated by the SARS-CoV-2 replicon system. To validate the binding mode via docking, the mutation experiment, circular dichroism (CD), enzymatic inhibition and surface plasmon resonance (SPR) assay were performed, demonstrating that methyl rosmarinate bound to the allosteric site of SARS-CoV-2 3CLpro. In conclusion, this paper provides the new ideas for the rapid discovery of active ingredients in TCM prescriptions based on a specific target, and methyl rosmarinate has the potential to be developed as an antiviral therapeutic candidate against SARS-CoV-2 infection.

Atomically Dispersed Dual-Metal ORR Catalyst with Hierarchical Porous Structure for Zn-Air Batteries.

The metal-nitrogen-carbon (M-N-C)-based catalysts are promising to replace PGM (platinum group metal) to accelerate oxygen reduction reaction due to their excellent electrocatalytic performance. However, the inferior intrinsic activity and poor active site density confining further improvement in their performance. Modulating the electronic structure and reasonably designing the pore structure are widely acknowledged effective strategies to boost the activity of the M-N-C catalysts. However, it is a great challenge to form abundant pores to regulate the electronic structure via the facile method. Herein, a hierarchical, porous dual-atom catalyst FeNi-NPC-1000 has been architectured by the Na2CO3 template method and bimetallic doping modification strategy. Benefitting from the optimized pore and electronic structure, the as-prepared FeNi-NPC-1000 possesses a high specific surface area (1412.8 m2 g-1) and improved ORR activity (E1/2 = 0.877 V vs RHE), which is superior to that of Pt/C (E1/2 = 0.867 V vs RHE). With the evidence of AC-STEM, XAS, and DFT, the FeNi-N8-C moiety is proven to be the key active site to realize high-efficiency ORR catalysis. When assembled it as an air cathode of ZABs, FeNi-NPC-1000 displays superior discharge performance (Pmax = 367.1 mW cm-2) and a stable battery long-life. This article will provide a new strategy for designing dual-metal atomic catalysts applied in metal-air batteries.

A review of nuclear Dbf2-related kinase 1 (NDR1) protein interaction as promising new target for cancer therapy.

Nuclear Dbf2-related kinase 1 (NDR1) is a nuclear Dbf2-related (NDR) protein kinase family member, which regulates cell functions and participates in cell proliferation and differentiation through kinase activity. NDR1 regulates physiological functions by interacting with different proteins. Protein-protein interactions (PPIs) are crucial for regulating biological processes and controlling cell fate, and as a result, it is beneficial to study the actions of PPIs to elucidate the pathological mechanism of diseases. The previous studies also show that the expression of NDR1 is deregulated in numerous human cancer samples and it needs the context-specific targeting strategies for NDR1. Thus, a comprehensive understanding of the direct interaction between NDR1 and varieties of proteins may provide new insights into cancer therapies. In this review, we summarize recent studies of NDR1 in solid tumors, such as prostate cancer and breast cancer, and explore the mechanism of action of PPIs of NDR1 in tumors.

Regulation of secondary metabolites in the endophytic fungus Penicillium sp. KMU18029 by the chemical epigenetic modifier 5-azacitidine.

The chemical epigenetic modifier 5-azacitidine (5-Aza C), a DNA methyltransferase inhibitor, was used to manipulate the endophytic fungus Penicillium sp. KMU18029. From its rice fermentation extract, a new polyketone compound (3S,4R)-3,4,8-trihydroxy-6-methyl-3,4-dihydronaphthalen-1(2H)-one (1), along with 13 known compounds, 3,4,8-trihydroxy-6-(hydroxymethyl)-3,4-dihydronaphthalen-1(2H)-one (2), decaturin B (3), 15-hydroxydecaturin A (4), oxalicine A (5), pileotin A (6), pyrandecarurin A (7), decaturenol A (8), decaturenoid (9), penisarins A (10), oxaline (11), (4E,8E)-N-D-2'-hydroxyocta-decanoyl-1-O-ß-D-glycopy-ranosyl-9-methyl-4,8-sphingadienine (12), ergosterol (13) and stigma-5-en-3-O-ß-glucoside (14), were separated. Among the known compounds, 2, 7, 12 and 14 were not found in our previous research on this strain. The structure of the new compound was identified by spectroscopic techniques such as HR-ESIMS, 1D NMR, 2D NMR and CD. Furthermore, all the isolated compounds were tested for their antimicrobial activities, and only compounds 1, 2 and 11 showed weak activities against S. aureus, with MICs of 128 µg/mL.

Danshensu inhibits SARS-CoV-2 by targeting its main protease as a specific covalent inhibitor and discovery of bifunctional compounds eliciting antiviral and anti-inflammatory activity.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to human. Since there are still no effective treatment options against the new emerging variants of SARS-CoV-2, it is necessary to devote a continuous endeavor for more targeted drugs and the preparation for the next pandemic. Salvia miltiorrhiza and its active ingredients possess wide antiviral activities, including against SARS-CoV-2. Danshensu, as one of the most important active ingredients in Salvia miltiorrhiza, has been reported to inhibit the entry of SARS-CoV-2 into ACE2 (angiotensin-converting enzyme 2)-overexpressed HEK-293T cells and Vero-E6 cells. However, there is a paucity of information regarding its detailed target and mechanism against SARS-CoV-2. Here, we present Danshensu as a covalent inhibitor of 3-chymotrypsin-like protease (3CLpro) against SARS-CoV-2 by the time-dependent inhibition assay (TDI) and mass spectrometry analysis. Further molecular docking, site-directed mutagenesis, circular dichroism (CD) and fluorescence spectra revealed that Danshensu covalently binds to C145 of SARS-CoV-2 3CLpro, meanwhile forming the hydrogen bonds with S144, H163 and E166 in the S1 site. Structure-based optimization of Danshensu led to the discovery of the promising compounds with good inhibitory activity and microsomal stability in vitro. Due to Danshensu inhibiting lung inflammation in the mouse model, we found that Danshensu derivatives also showed better anti-inflammatory activity than Danshensu in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Thus, our study provides not only the clue of the efficacy of Salvia miltiorrhiza against SARS-CoV-2, but also a detailed mechanistic insight into the covalent mode of action of Danshensu for design of covalent inhibitors against SARS-CoV-2 3CLpro, highlighting its potential as a bifunctional molecule with antivirus and anti-inflammation.

Interplay of IL-33 and IL-35 Modulates Th2/Th17 Responses in Cigarette Smoke Exposure HDM-Induced Asthma.

Cigarette smoke (CS) facilitates adverse effects on the airway inflammation and treatment of asthma. Here, we investigated the mechanisms by which CS exacerbates asthma. The roles of IL-33 and IL-35 in asthma development were examined by treatment with IL-33 knockout (IL-33 KO) or transfection of adenovirus encoding IL-35 (Ad-IL-35) in a murine model of cigarette smoke-exposure asthma. Furthermore, the involvement of IL-33 and IL-35 in regulating DCs and Th2/Th17 cells was examined in a coculture system of DCs with CD4+ T cells. Additionally, we observed the effect of CpG-ODNs on the balance of IL-33 and IL-35. We show that CS and house dust mite (HDM) exposure induced IL-33 and suppressed IL-35 levels in cigarette smoke-exposure asthma in vivo and in vitro. Treatment with IL-33 KO or Ad-IL-35 significantly attenuated airway hyperreactivity, goblet hyperplasia, airway remodelling, and eosinophil and neutrophil infiltration in the lung tissues from asthmatic mice. Furthermore, we demonstrated reciprocal regulation between CS and HDM-modulated IL-33 and IL-35. Mechanistically, IL-33 KO (or anti-ST2) and Ad-IL-35 attenuated Th2- and Th17-associated inflammation by downregulating TSLP-DC signalling. Finally, administration of CpG-ODNs suppressed the expression of IL-33/ST2 and elevated the levels of IL-35, which is mainly derived from CD4+Foxp+ Tregs, to alleviate Th2- and Th17-associated inflammation by inhibiting the activation of BMDCs. Taken together, the IL-33/ST2 pathway drives the DC-Th2 and Th17 responses of cigarette smoke-exposure asthma, while IL-35 has the opposite effect. CpG-ODNs represent a potential therapeutic strategy for modulating the balance of IL-33 and IL-35 to suppress allergic airway inflammation.

Fungal polyketides produced by an endophytic fungus Phoma sp. associated with Gastrodia elata.

Two novel fungal polyketides, phometides A (1) and B (2), together with four known compounds (3-6), were isolated from the endophytic fungus Phoma sp. YUD17001 obtained from Gastrodia elata Blume. The structures were elucidated based on spectroscopic analyses, X-ray crystal diffraction, and time-dependent density functional theory/electronic circular dichroism (TDDFT/ECD) calculations. Structurally, phometide A (1) represented the first example of C12 polyketide characterized by an unusual tetrahydrobenzofuran-3(2H)-one core with an α,ß-unsaturated ketone functionality, while phometide B (2) was an unprecedented molecule containing a 2-pentylcycloheptan-1-one scaffold. In an antimicrobial activity assay, phometide A (1) exhibited significant inhibitory activity against Staphylococcus aureus with MIC value of 4 µg/mL. Phometide B (2) showed moderate antifungal activity against Candida albicans with an MIC value of 16 µg/mL. Furthermore, compounds 1 and 2 were evaluated for their acetylcholinesterase inhibitory and cytotoxic activities.

Novel Method for Optimization Cement Slurry Based on the Wellbore Integrity Model in High-Temperature and High-Pressure Conditions.

The integrity of the cement sheath is crucial for ensuring the long-term safe and efficient production of oil and gas wells. The mechanical properties of the cement sheath are improved by optimizing the cement slurry to match the actual operating conditions, further enhancing the wellbore integrity. In high-temperature and high-pressure (HTHP) conditions, a mechanics model of casing-cement sheath-formation was developed based on the thick-walled cylinder theory, considering the coupling effect of temperature and pressure as well as elastic and plastic deformation of the cement sheath. The relationship between the mechanical parameters of the cement sheath, such as elastic modulus, Poisson's ratio, and yield strength, and casing pressure under different temperatures was analyzed based on the simulation results. A control chart of the mechanical properties of the cement sheath under high-temperature and high-pressure environments was subsequently developed. It was concluded that the elastic deformation of the cement sheath occurs first followed by plastic deformation as the casing pressure increases, corresponding to the yielding point of tangential stress on the cement sheath. The cement sheath is more prone to failure in high-temperature conditions due to thermal stress. Sensitivity analysis revealed that a cement sheath with a low elastic modulus and high yield strength contributes to enhancing its integrity. The developed control chart enables a quick and quantitative estimation of whether the cement sheath meets the requirements of downhole conditions. Most importantly, the cement slurry is optimized, based on the theoretical method, to improve the seal integrity of the cement sheath. This study provides a quantitative evaluation of cement slurry optimization and offers practical guidance for managing the wellbore integrity by identifying the mechanical parameters of cement sheaths under operating conditions.

Evaluation of bioequivalence and safety analysis of capecitabine tablets and Xeloda® under postprandial dosing conditions in Chinese patients with solid tumor.

OBJECTIVES: To compare the pharmacokinetic and safety of the test group capecitabine tablets (0.5 g) and the reference group capecitabine tablets (0.5 g). METHODS: This study was registered at www.chinadrugtrials.org.cn under the registration number CTR20220138. 48 subjects with solid tumor were recruited and randomized to receive either the test group or the reference group at a dose of 2 g per cycle for three cycles of the entire trial. RESULTS: The point estimate of the geometric mean ratio of Cmax for the subject and reference groups was 1.0670, which was in the range of 80.00%-125.00%. And the upper limit of 95% confidence interval was -0.0450 < 0. The statistics of geometric mean ratio of AUC0-t and AUC0-∞ (test group/reference group) and their 90% confidence intervals were in the range of 80.00%-125.00%, thus the test group was bioequivalent to the reference group under the conditions of this postprandial test. There were no major or serious adverse events. Conclusion: The pharmacokinetic profiles of capecitabine under postprandial conditions were consistent between the two groups. The two groups were bioequivalent and had a similar favorable safety profile in Chinese patients with solid tumor.