Human epididymal protein 4 and its combined detection show good diagnostic value in lung cancer: A retrospective study.

OBJECTIVES: This study aimed to assess the diagnostic value of human epididymal protein 4 (HE4), a potential novel biomarker for lung cancer, and its combined detection with five other conventional biomarkers in lung cancer diagnosis and subtyping. METHODS: In this retrospective study, 115 lung cancer patients, 50 patients with benign pulmonary disease, and 50 healthy controls were included. Serum HE4, progastrin-releasing peptide (ProGRP), squamous cell carcinoma (SCC) antigen, cytokeratin-19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) were analyzed using the electrochemiluminescence immunoassay and chemiluminescence immunoassay. The receiver operating characteristic curve was performed to analyze the diagnostic efficacy of individual biomarkers in identifying both lung cancer and its histologic subtypes. RESULTS: All six biomarkers showed significantly elevated levels in the lung cancer group compared to both benign pulmonary disease and control groups (P < 0.05). Among the biomarkers evaluated, HE4 exhibited the highest diagnostic performance for lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma with area under the curve (AUC) values of 0.921, 0.891, and 0.937, respectively. ProGRP was the optimal biomarker for small cell lung cancer with an AUC of 0.973. The combination of all six biomarkers yielded the largest AUCs in the diagnosis of lung cancer subtypes (0.937 for lung adenocarcinoma, 0.998 for lung squamous cell carcinoma, and 0.985 for small cell lung cancer). Furthermore, specific combinations, such as HE4 + CEA, HE4 + SCC, and ProGRP + HE4 + NSE, showed strong diagnostic performance in lung cancer. CONCLUSIONS: HE4 and its combined detection held substantial clinical significance in the diagnosis of lung cancer and its histologic subtyping, especially for lung adenocarcinoma and lung squamous cell carcinoma.

Adaptive and Robust Vitrimers Fabricated by Synergy of Traditional and Supramolecular Polymers.

Vitrimers offer a unique combination of mechanical performance, reprocessability, and recyclability that makes them highly promising for a wide range of applications. However, achieving dynamic behavior in vitrimeric materials at their intended usage temperatures, thus combining reprocessability with adaptivity through associative dynamic covalent bonds, represents an attractive but formidable objective. Herein, we couple boron-nitrogen (B-N) dative bonds and B-O covalent bonds to generate a new class of vitrimers, boron-nitrogen vitrimers (BNVs), to endow them with dynamic features at usage temperatures. Compared with boron-ester vitrimers (BEVs) without B-N dative bonds, the BNVs with B-N dative bonds showcase enhanced mechanical performance. The excellent mechanical properties come from the synergistic effect of the dative B-N supramolecular polymer and covalent boron-ester networks. Moreover, benefiting from the associative exchange of B-O dynamic covalent bonds above their topological freezing temperature (Tv), the resultant BNVs also possess the processability. This study leveraged the structural characteristics of a boron-based vitrimer to achieve material reinforcement and toughness enhancement, simultaneously providing novel design concepts for the construction of new vitrimeric materials.

Adaptisorption of Nonporous Polymer Crystals.

Although our knowledge and understanding of adsorptions in natural and artificial systems has increased dramatically during the past century, adsorption associated with nonporous polymers remains something of a mystery, hampering applications. Here we demonstrate a model system for adaptisorption of nonporous polymers, wherein dative B-N bonds and host-guest binding units act as the kinetic and thermodynamic components, respectively. The coupling of these two components enables nonporous polymer crystals to adsorb molecules from solution and undergo recrystallization as thermodynamically favored crystals. Adaptisorption of nonporous polymer crystals not only extends the types of adsorption in which the sorbate molecules are integrated in a precise and orderly manner in the sorbent systems, but also provides a facile and accurate approach to the construction of polymeric materials with precise architectures and integrated functions.

Enhancing the Toughness and Strength of Polymers Using Mechanically Interlocked Hydrogen Bonds.

The energy dissipative features of hydrogen bonds under conditions of mechanical strain have provided an ongoing incentive to explore hydrogen bonding units for the purpose of controlling and customizing the mechanical properties of polymeric materials. However, there remains a need for hydrogen bond units that (1) possess directionality, (2) provide selectivity, (3) dissipate energy effectively, and (4) can be incorporated readily into polymeric materials to regulate their mechanical properties. Here, we report mechanically interlocked hydrogen bond units that incorporate multiple hydrogen bonds within a [2]catenane structure. The conformational flexibility and associated spatial folding characteristics of the [2]catenane units allow for molecular scale motion under external stress, while the interlocked structure serves as a pivot that maintains the directionality and selectivity of the resultant hydrogen bonding units. When incorporated into polymers, these interlocked hydrogen bond motifs serve to strengthen and toughen the resulting materials. This study not only presents a novel hydrogen bond unit for creating polymeric materials with improved mechanical properties but also underscores the unique opportunities that mechanically interlocked hydrogen bond structures may provide across a diverse range of applications.

A 3D Cross-Linked Metal-Organic Framework (MOF)-Derived Polymer Electrolyte for Dendrite-Free Solid-State Lithium-Ion Batteries.

Lithium metal batteries (LMBs) with high energy density have received widespread attention; however, there are usually issues with lithium dendrite growth and safety. Therefore, there is a demand for solid electrolytes with high mechanical strength, room-temperature ionic conductivity, and good interface performance. Herein, a 3D cross-linked metal-organic framework (MOF)-derived polymer solid electrolyte exhibits good mechanical and ionic conductive properties simultaneously, in which the MOF with optimized pore size and strong imidazole cation sites can restrict the migration of anions, resulting in a uniform Li+ flux and a high lithium-ion transference number (0.54). Moreover, the MOF-derived polymer solid electrolytes with the 3D cross-linked network can promote the rapid movement of Li+ and inhibit the growth of lithium dendrites. Lithium symmetric batteries assembled with the 3D MOF-derived polymer solid electrolytes are subjected to lithium plating/stripping and cycled over 2000 h at a current density of 0.1 mA cm-2 and over 800 h at a current density of 0.2 mA cm-2 . The Li/P-PETEA-MOF/LiFePO4 batteries exhibit excellent long-cycle stability and cycle reversibility.

Applications of macrocycle-based solid-state host-guest chemistry.

Macrocyclic molecules have been used in various fields owing to their guest binding properties. Macrocycle-based host-guest chemistry in solution can allow for precise control of complex formation. Although solution-phase host-guest complexes are easily prepared, their limited stability and processability prevent widespread application. Extending host-guest chemistry from solution to the solid state results in complexes that are generally more robust, enabling easier processing and broadened applications. Macrocyclic compounds in the solid state can encapsulate guests with larger affinities than their soluble counterparts. This is crucial for use in applications such as separation science and devices. In this Review, we summarize recent progress in macrocycle-based solid-state host-guest chemistry and discuss the basic physical chemistry of these complexes. Representative macrocycles and their solid-state complexes are explored, as well as potential applications. Finally, perspectives and challenges are discussed.

Efficacy and safety of different PD-1 inhibitors in combination with lenvatinib in the treatment of unresectable primary liver cancer: a multicentre retrospective study.

Immune checkpoint inhibitors (ICIs) are safe and efficacious treatments for advanced primary liver cancer (PLC). The efficacy of different ICIs in the treatment of liver cancer remains unclear. The purpose of this study was to explore whether there is a difference in the efficacy and safety of various programmed cell death protein 1 (PD-1) inhibitors in combination with lenvatinib in the treatment of unresectable PLC. Patients with PLC treated with lenvatinib in combination with PD-1 inhibitors (camrelizumab, tislelizumab, sintilimab, or pembrolizumab) between January 2018 and December 2021 were retrospectively enrolled. Tumor response, adverse events, and grades were evaluated. Kaplan-Meier analysis and log-rank test were used to compare the overall survival and progression-free survival of patients treated with different PD-1 inhibitors. Cox regression analysis was used for univariate and multivariate analyses to identify clinical variables related to treatment efficacy. This study included a total of 176 patients who received a combination of lenvatinib and PD-1 inhibitors. Of these, 103 patients received camrelizumab, 44 received tislelizumab, 20 received sintilimab, and 9 received pembrolizumab. There was no significant difference in the pairwise comparison of camrelizumab, tislelizumab, sintilimab, and pembrolizumab using Kaplan-Meier survival analysis. Adverse events occurred in 40 (22.7%) patients (grade ≥ 3, 2.3%). The incidence of grade 3 adverse events among the four PD-1 inhibitor groups was below 5%. Camrelizumab, tislelizumab, sintilimab, and pembrolizumab are viable options for patients with unresectable PLC. These PD-1 inhibitors in combination with lenvatinib showed good safety profiles. The results guide selecting treatment for patients with unresectable PLC.

Improvement of obesity-induced fatty liver disease by intermittent hypoxia exposure in a murine model.

Background: The high prevalence of non-alcoholic fatty liver disease (NAFLD) in the world raises an important concern for human health. The western diet containing high fat and fructose is the risk factor for NAFLD development. Intermittent hypoxia (IH), known as the basis of obstructive sleep apnea (OSA), normally is correlated with impaired liver function. However, the role of IH in liver injury prevention has been revealed by many other studies based on the different IH paradigms. The current study, therefore, tests the impact of IH on the liver of high-fat and high-fructose diet (HFHFD) fed mice. Material and Method: Mice were exposed to IH (2 min cycle, FiO2 8% for 20 s, FiO2 20.9% for 100 s; 12 h/day) or intermittent air (FiO2 20.9%) for 15 weeks, with normal diet (ND) or high-fat and high-fructose diet (HFHFD). Indices of liver injury and metabolism were measured. Results: IH causes no overt liver injury in mice fed an ND. However, HFHFD-induced lipid accumulation, lipid peroxidation, neutrophil infiltration, and apoptotic process were significantly attenuated by IH exposure. Importantly, IH exposure altered bile acids composition and shifted the hepatic bile acids towards FXR agonism, which was involved in the protection of IH against HFHFD. Conclusion: These results support that the IH pattern in our model prevents liver injury from HFHFD in experimental NAFLD.

Case report: Long-read sequencing identified a novel 14.9-kb deletion of the α-globin gene locus in a family with α-thalassemia in China.

Background: Thalassemia is a hereditary blood disease resulting from globin chain synthesis impairment because of α- and/or ß-globin gene variants. α-thalassemia is characterized by non-deletional and deletional variants in the HBA gene locus, of which rare deletional variants are difficult to detect by conventional polymerase chain reaction (PCR)-based methods. Case report: We report the case of a one-month-old boy, who and his mother had abnormal hematological parameters, while his father had normal hematology. Conventional PCR-reverse dot blot (RDB) was performed for all family members to analyze the 23 most common thalassemia variants in China, but did not identify any pathologic variants. Single-molecule real-time (SMRT) long-read sequencing (LRS) technology was then performed and identified an unreported 14.9-kb large deletion (hg38 chr16:168,803-183,737) of the α-globin gene locus, which disrupted both HBA1 and HBA2 genes in the proband and his mother. The exact breakpoints of the deletion were confirmed by gap-PCR and Sanger sequencing. Conclusion: We have detected a novel large deletion in α-globin gene locus in China, which not only enriches the variant spectrum of thalassemia, but also demonstrates the accuracy and efficiency of LRS in detecting rare and novel deletions.

An Asymmetric Cross-Linked Ionic Copolymer Hybrid Solid Electrolyte with Super Stretchability for Lithium-Ion Batteries.

Composite solid electrolytes are recommended to be the most promissing strategy for solid-state batteries because they combine the advantages of inorganic ceramics and polymers. However, the huge interfacial resistance between the inorganic ceramic and polymer results in low ionic conductivity, which is still the major impediment that limits their applications. Herein, a novel highly elastic and weakly coordinated ionic copolymer hybrid electrolyte with asymmetric structure based on surface-modified Li1.5 Al0.5 Ge1.5 (PO4 )3 by "in situ" polymerization is proposed to improve ionic conductivity and mechanical properties simultaneously. The all-solid hybrids electrolytes exhibit room-temperature ionic conductivity up to 2.61 × 10-4 S cm-1 and lithium-ion transference number of 0.41. The hybrids electrolytes can be repeatedly stretching-releasing-stretching, showing a super stretchability with the elongation at break up to 496%. The Li symmetrical cells assembled with the hybrid electrolytes can continuously operate for 800 h at 0.1 mA cm-2 without discernable dendrites, indicating good interfacial compatibility between the hybrid electrolytes and lithium electrodes. The Li|LiFePO4 batteries assembled with the hybrid electrolytes deliver an initial discharge specific capacity of 165.5 mAh g-1 with an initial coulombic efficiency of 94.8% and 154 mAh g-1 after 100 cycles at 0.1 C, and maintain 95.4% capacity retention after 100 cycles at 0.5 C.

De-escalation or discontinuation of tyrosine kinase inhibitor in patients with chronic myeloid leukemia: A multicentral, open-label, prospective trial in China.

Background: Long-term treatment-free remission (TFR) represents a new goal for chronic myeloid leukemia (CML). Optimizing dose of tyrosine kinase inhibitors (TKIs) in the CML treatment maybe a new challenge to maintain effective and improving patients' quality of life. We hypothesized that administration of low-dose TKIs does not compromise major molecular response (MMR) in patients with CML who have a deep molecular response (DMR). Methods: We did an open-label, randomized trial at eight hospitals in China. Eligible CML-CP patients (aged 18-70 years) had shown continuous response to TKI more than 5 years and maintained MR4.5 (BCR-ABLIS ≤ 0.0032%) in recent 18 months. Patients were randomly assigned (1:1) to the TKI de-escalation group or the discontinuation group. Randomization was done with permuted blocks (block size four) and implemented through an interactive web-based randomization system. Recurrence was defined as the single sample with real time Quantitative PCR (RT-qPCR) measurement greater than 0.1% (MMR). The primary endpoint was 12-month MMR rate in patients who received de-escalation or discontinuation of TKIs. This study was registered at ClinicalTrials.gov (NCT04143087). Results: Around 125 patients were enrolled between October 23, 2019 and October 31, 2020, 62 patients received dose de-escalation of TKIs, while 63 patients in the discontinuation group. In the de-escalation group, molecular recurrence-free survival at 12 months was 88.32% (95% CI 79%-98%), whereas molecular recurrence-free survival in the discontinuation group at 12 months was 59.98% (95% CI 47-73). No progressions occurred at the data cut-off date. All 29 recurrence cases restart TKI treatment returned to MMR. Cytolytic NK cells as a proportion of lymphocyte cells were significantly increased from baseline after 6 months whether in the de-escalation or TKIs cessation group (P = 0.048, 0.001, respectively); compared with the relapsing patients, Tregs proportion was decreased (P = 0.003), and higher proportion of NK cells were found in non-relapsing patients whether in TKI de-escalation or discontinuation group (P = 0.011, 0.007, respectively). We also found that the de-escalation group showed better disease-specific HRQOL in regards to its impact on emotional functioning, fatigue, pain, and financial difficulties. Conclusion: With 88.32% MMR in 12-months follow-up after de-escalation TKIs' treatment, dose-halving could become a new treatment paradigm for CML patients who with DMR under continuing maintenance therapy with TKIs.

Small intestinal bacterial overgrowth is associated with clinical relapse in patients with quiescent Crohn's disease: a retrospective cohort study.

Background: Crohn's disease (CD) is an irreversible inflammatory disorder, characterized by alternating periods of relapse and remission. It is particularly important to predict clinical relapses in patients with CD because patients in remission could relapse frequently in a randomized way. Small intestinal bacterial overgrowth (SIBO) is a symptom of gut microbial dysbiosis and is commonly observed in patients with CD, which may affect disease course. The present research was carried out to establish whether SIBO is linked to the subsequent clinical relapse of CD. Methods: This retrospective observational cohort research included consecutive patients (≥18 years) with quiescent CD who underwent lactulose hydrogen-methane breath test to diagnose SIBO managed at Jinling Hospital in China from January 2016 to June 2020. We assessed demographic data, laboratory parameters, SIBO and clinical characteristics including disease location and behavior, surgical history and current and previous medication at baseline and analyzed these data to identify factors associated with clinical relapse. Patients were followed up for 18 months and assessed for the Crohn's Disease Activity Index (CDAI) scores, treatment escalation, and disease progression to determine the primary endpoint of clinical relapse. Results: Of the 73 enrolled patients, 34 (46.6%) were positive for SIBO. Twenty-seven (37.0%) patients experienced clinical relapse within 18 months (median time of relapse: 13.9 months). SIBO in the relapse group was considerably elevated compared to the non-relapse group (63.0% vs. 37.0%, P=0.032). The multivariate Cox regression analysis showed that SIBO [hazard ratio (HR) 2.79, P=0.017] and penetrating disease behavior (HR 3.66, P=0.040) were the sole individual risk elements for relapse in patients with quiescent CD. Conclusions: This study indicated that SIBO was highly prevalent in patients with CD, and was independently linked to clinical relapse in quiescent patients. Detecting SIBO may be a valuable option for the prognostic assessment of patients in clinical remission.

Digital biosensor for human cerebrospinal fluid detection with single-use sensing strips.

Leakage of human cerebrospinal fluid (CSF) caused by trauma or other reasons presents exceptional challenges in clinical analysis and can have severe medical repercussions. Conventional test methods, including enzyme-linked immunosorbent assay and immunofixation electrophoresis testing, typically are performed at a few clinical reference laboratories, which may potentially delay proper diagnosis and treatment. At the same time, medical imaging can serve as a secondary diagnosis tool. This work presented here reports the use of a point-of-care electrochemical sensor for detection of beta-2-transferrin (B2T), a unique isomer of transferrin that is present exclusively in human CSF but is absent in other bodily fluids. Limits of detection were examined via serial dilution of human samples with known B2T concentrations down to 7 × 10-12 g B2T/ml while maintaining excellent sensitivity. Nine human samples with varying levels of B2T were compared using up to 100 times dilution to confirm the validity of sensor output across different patient samples.

Mechanically interlocked polymers based on rotaxanes.

The nature of mechanically interlocked molecules (MIMs) has continued to encourage researchers to design and construct a variety of high-performance materials. Introducing mechanically interlocked structures into polymers has led to novel polymeric materials, called mechanically interlocked polymers (MIPs). Rotaxane-based MIPs are an important class, where the mechanically interlocked characteristic retains a high degree of structural freedom and mobility of their components, such as the rotation and sliding motions of rotaxane units. Therefore, these MIP materials are known to possess a unique set of properties, including mechanical robustness, adaptability and responsiveness, which endow them with potential applications in many emerging fields, such as protective materials, intelligent actuators, and mechanisorption. In this review, we outline the synthetic strategies, structure-property relationships, and application explorations of various polyrotaxanes, including linear polyrotaxanes, polyrotaxane networks, and rotaxane dendrimers.

Positive association of nap duration with risk of non-alcoholic fatty liver disease in an occupational population in Guangdong Province, China: a cross-sectional study.

BACKGROUND: A lack of sleep or disorder in sleep-wake cycles has been associated with metabolic impairments. However, few studies have investigated the association between daytime napping duration and the risk of non-alcoholic fatty liver disease. This study aimed to investigate the association of daytime napping duration with the risk of non-alcoholic fatty liver disease in a Chinese population. METHODS: This cross-sectional study analyzed data from the Health Management Center of Nanfang Hospital, Guangdong Province. A total of 3363 participants aged 20-79 years were recruited and admitted from January 20, 2018, to October 16, 2020. Non-alcoholic fatty liver disease was diagnosed using abdominal ultrasonography. The outcome was the association between daytime sleep duration and the risk of non-alcoholic fatty liver disease. RESULTS: Compared with non-nappers, long daytime nappers (≥ 60 min) were associated with a higher risk of non-alcoholic fatty liver disease in the crude model (odds ratio 2.138; 95% confidence interval 1.88-2.61, P < 0.05) and in the multivariable adjustment model (odds ratio 2.211; 95% confidence interval 1.042-4.690, P < 0.05) after adjusting for demographic, educational, and metabolic risk factors. The association was moderately enhanced with additional adjustments for night sleep duration and socioeconomic or other factors (odds ratio 2.253; 95% confidence interval 1.061-4.786, P = 0.035). CONCLUSION: In this cross-sectional study, daytime napping duration of ≥ 60 min was positively associated with the risk of non-alcoholic fatty liver disease in an occupational population of Guangdong Province after multivariable adjustment.

Tea Consumption is Associated with an Increased Risk of Hyperuricemia in an Occupational Population in Guangdong, China.

Purpose: Chronic hyperuricemia leads to long-term deposition of monosodium urate crystals that may damage the joint structure and affect quality of life. Although hyperuricemia prevalence varies, most studies indicate increased cases of hyperuricemia worldwide. The relationship between hyperuricemia and tea consumption is uncertain. This cross-sectional study investigated the effect of tea consumption on the risk of hyperuricemia in the working population in Guangdong, China. Patients and Methods: Data on weight, height, blood pressure, laboratory test results, and health questionnaire responses of 7644 adults aged ≥18 years were obtained from the health examinee dataset of Nanfang Hospital. The characteristics of subjects with and without hyperuricemia were compared using t-tests or non-parametric Mann-Whitney U-tests for continuous variables and chi-square tests for categorical variables. Relationships between hyperuricemia and participant characteristics (sex, age, education level, smoking history, alcohol consumption, hypertension, body mass index, tea consumption, and other dietary factors) were examined using univariate and multivariate logistic regression models to identify independent risk factors for hyperuricemia. Results: Tea consumption was associated with a higher risk of hyperuricemia in the crude model (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.48-2.05, once a month through twice a week vs never, P<0.001; OR 2.44, 95% CI 2.07-2.89, ≥3 times a week vs never, P<0.001). The adjusted OR for hyperuricemia was 1.30 (95% CI 1.08-1.56, P=0.006) in participants who consumed tea once a month through twice a week and 1.35 (95% CI 1.11-1.64, P=0.003) in those who consumed tea ≥3 times a week compared with the "never" reference group after adjusting for sociodemographic factors, anthropometric and biochemical indices, and dietary factors. This relationship remained significant in men but not women in subgroup analysis. Conclusion: Tea consumption is an independent risk factor for hyperuricemia and is more pronounced in men than women.

[Evaluation of the Nurses' Utilization of the Pain Management Information System Based on the Information System Success Model].

BACKGROUND: Pain records provide important data to medical teams to guide their provision of pain management interventions. Incomplete records and records that do not integrate pain data will affect patient safety. Use of information technology helps facilitate communication within the medical team and improve quality of care. PURPOSE: This study was designed to evaluate the effectiveness of a pain management information system. METHODS: The questionnaire survey method was employed in this study. The system-evaluation questionnaire was designed based on the six dimensions of the information system success model (ISSM), including system quality, information quality, service quality, intention to use, user satisfaction, and net benefits. Three months after the pain management system was implemented, the opinions of 282 nurses from a medical center in central Taiwan were collected. Research data were analyzed using descriptive and inferential statistical methods. RESULTS: Of the six dimensions, "information quality" received the highest average score (4.71). The two dimensions of "intention to use" and "user satisfaction" had the highest correlation with "net benefits". "User satisfaction" was found to have the highest predictive power for the "net benefits" of the system, with an explanatory power of about 81.2%. CONCLUSIONS: The pain management system considered in this study was shown to provide complete and accurate pain management information, which is an important factor affecting nurses' intention to use and satisfaction. The evaluation results based on the ISSM show the pain management system to be a good information system that generates accurate information and has a high intention-to-use rate and high rate of user satisfaction.

A new coumarin isolated from the roots of Heracleum dissectum Ledeb.

A new coumarin named (9 R, 10 R)-9, 10-dihydro-10-hydroxy-9-methoxy-bergapten (1) and 13 known compounds (2-14) were isolated from the roots of Heracleum dissectum Ledeb., in which compounds (2-13) were obtained from H. dissectum for the first time. Their structures were illuminated by HR-ESI MS, 1 D and 2 D NMR, optical rotation and comparison with literatures. All compounds were evaluated against hepatocellular carcinoma HepG2 cell lines and the results showed that candinol C (8) had moderate cytotoxic activity against HepG2 cells with IC50 value at 57.6 ± 1.1 µM.