C-Reactive protein(CRP)is an important acute-phase response protein,which is widely used in the assessment of inflammation and cardiovascular disease risk,and acts as a pathogenic factor directly involved in the disease process of certain conditions.Therefore,developing immunosuppressants targeting CRP or investigating its pathogenic mechanisms is of significant importance.Most B-cell epitopes are conformational epitopes,and studying conformational epitopes is typically challenging.To date,no methods have been reported for mapping the conformational epitopes of CRP in solution.In this study,a rapid strategy was developed for studying conformational epitopes by combining hydrogen/deuterium exchange mass spectrometry(HDX-MS)with multiparametric prediction of B-cell epitopes and protein secondary structure analysis.This approach was successfully applied to the binding sites and allosteric targets of the 115 kDa full pentameric CRP and the clinically used monoclonal antibody(mAb)5A8.The results showed that the amino acid residues 84-103,138-146,and 165-173 together form the potential conformational epitopes for mAb 5A8 on CRP,while the amino acid residues 21-32 and 175-178 were identified as potential allosteric targets.The discovery of the mAb 5A8 binding sites and allosteric targets was crucial for improving clinical diagnostic capabilities.Experimental results demonstrated that this workflow allowed rapid conformational epitope mapping of CRP under near-physiological conditions,with advantages such as high speed,high sensitivity,and high throughput.

A pyrene-phenol-based fluorescent probe PyP which showed typical intramolecular charge transfer(ICT)and monomer-excimer activities was synthesized by using pyrene carboxaldehyde hydrazone and 4-tert-butyl-2,6-diformylphenol as the raw materials.The effects of solvents on PyP were studied,and the results showed that the color of protic polar solvents(Ethanol,N,N-dimethylformamide,methanol and H2O)were successfully identified.Based on the solvent polarity-regulated PyP monomer-excimer switching,the rapid and highly sensitive ratiometric probe,"Turn-off"and"Turn-on"multimodal probes were established for detection of trace water content in organic solvents(Dimethyl sulfoxide,N,N-dimethylformamide,ethanol and methanol),with detection limits(3σ/k)of 0.0021％,0.046％,0.062％and 0.024％.The method was successfully used to detect water content in dimethyl sulfoxide,N,N-dimethy lformamide,ethanol and methanol commercial organic solvents,with recoveries ranging from 97.2％to 108.0％.The developed method showed good accuracy and stability,and had good application prospect.

After the wooden shipwreck was recovered from the marine underwater environment,the wooden components undergo varying degrees of degradation,therefore,accurately determining the extent of degradation is a fundamental scientific issue for implementing effective preservation strategies.In this work,the wooden remains of Pinus massoniana excavated from the"Nanhai No.1"shipwreck(Southern Song Dynasty)were investigated and compared with the modern wood to discriminate the degradation levels of archaeological wood using attenuated total reflection Fourier transform infrared(ATR-FTIR)spectroscopy.The residual sugar content within wood cell walls was determined using a non-invasive automated microscale ATR-FTIR method to extract chemical information from the wood tangential section.Microstructural characterization of wood samples was conducted by super depth of field microscopy and scanning electron microscopy.FTIR spectral analysis was performed to evaluate the degradation state and elucidate changes in cellulose crystallinity.Finally,the combination of FTIR spectroscopy with the sparse partial least squares discriminant analysis(sPLS-DA)model facilitated the rapid discrimination of degradation levels in shipwreck archaeological wood,and the performance of the model was evaluated using receiver operating characteristic(ROC)curves and area under the curve(AUC).The results showed that the higher the degree of wood degradation,the lower the residual sugar content in the wood cell wall,and the residual glucose content of highly degraded wood was only 4.7％.Significant differences were observed in both the tangential section microstructure and FTIR characteristic absorption patterns across degradation levels,and as the degradation advanced,progressive cell wall loosening occurred alongside selective removal of polysaccharide components,and the relative lignin content was increased,resulting in an elevated A1509/A1370 ratio in FTIR spectra.The sPLS-DA model achieved excellent discrimination performance with AUC values exceeding 0.9,confirming that the combination of FTIR spectroscopy with sPLS-DA enabled accurate assessment of degradation levels in shipwreck archaeological wood.This study developed a rapid and accurate methodology for assessing degradation levels in shipwreck archaeological wood based on microscale ATR-FTIR spectroscopy,which would help to promote the accurate assessment of the preservation state of waterlogged wooden artifacts.

AIM To explore the clinical effects of Jinfukang Oral Liquid combined with thymosin α1 on patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin.METHODS Seventy-five patients were randomly assigned into thymosin α1 group(15 cases)for 4-week administration,Jinfukang Oral Liquid group(30 cases)for 4-week administration,and combination group(30 cases)for 4-week administration.The changes in TCM clinical syndrome effects,immunity indices(CD3+T,Th,CTL,total NK,CD56dim CD16+NK,NKT,Treg,MDSC),lethality/inhibition ratios(CTL/Treg,total NK/Treg,NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC)and FACT-L scores were detected.RESULTS The Jinfukang Oral Liquid group and combination group demonstrated higher total effective rates than the thymosin α1 group(P＜0.05).After the treatment,the Jinfukang Oral Liquid group and combination group displayed increased NKT(P＜0.05)and decreased MDSC(P＜0.05),which were more obvious than those in the thymosin α1 group(P＜0.05),and higher NKT was observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group and combination group displayed increased lethality/inhibition ratios(P＜0.05),among which NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC were higher than those in the thymosin α1 group(P＜0.05),and higher CTL/MDSC,NKT/MDSC were observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group(except for physiological status,society and family status)and combination group(except for society and family status)displayed increased FACT-L scores(P＜0.05).CONCLUSION For the patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin,Jinfukang Oral Liquid single use or combined with thymosin α1 can enhance peripheral blood immune surveillance,inhibit immune escape,restore the balanced state of tumor immune responses,and improve TCM syndromes and life quality.

Amino acid metabolism plays a critical role in the progression and development of breast cancer. Cancer cells, including those in breast cancer, reprogram amino acid metabolism to meet the demands of rapid proliferation, survival, and immune evasion. This includes alterations in the uptake and utilization of amino acids, such as glutamine, serine, glycine, and arginine, which provide essential building blocks for biosynthesis, energy production, and redox homeostasis. Notably, the metabolic phenotypes of breast cancer cells vary across molecular subtypes and disease stages, emphasizing the need for patient stratification and personalized therapeutic strategies. Advances in multi-level diagnostics, including phenotyping and predictive tools, such as AI-based analysis and body fluid profiling, have highlighted the potential for tailoring treatments to individual metabolic profiles. Enzymes, such as glutaminase and serine hydroxymethyltransferase, often upregulated in breast cancer, represent promising therapeutic targets. Understanding the interplay between amino acid metabolism and breast cancer biology, alongside the integration of personalized medicine approaches, can uncover novel insights into tumor progression and guide the development of precision therapies. This review explores the metabolic pathways of amino acids in breast cancer, with a focus on their implications for personalized treatment strategies.
Humans ; Breast Neoplasms/therapy* ; Female ; Amino Acids/metabolism*

OBJECTIVE: Investigating the clinical efficacy of treating dorsally displaced distal radial double-column Die-punch fractures using a dorsal approach external fixator combined with Kirschner wires. METHODS: Retrospectively analyzed the clinical data of 15 patients with distal radial double-column Die-punch fractures treated with an external fixator combined with Kirschner wire between July 2020 and January 2023. There were 10 males and 5 females;6 cases on the left side and 9 on the right;age ranged from 22 to 76 years old. Recorded the preoperative and the final follow-up Cooney wrist function scores for the patients. The fracture healing time, and occurrence of complications were recorded. RESULTS: All 15 patients were followed up ranged from 12 to 16 months post-operation. All fractures achieved bony union, healing time ranging form 8 to 16 weeks. Not a single patient exhibited complications such as surgical site infection, fracture redislocation, or tendon injury. All individuals had their Kirschner wires and external fixation devices removed six weeks post-operatively and commenced rehabilitative therapy for wrist articulation. The Cooney wrist function scores at preoperative and ranged from 5 to 45 scores, at the latest follow-up ranged from 65 to 100 scores. At the final follow-up, the results were assessed as excellent in 10 patients, good in 4 patients, and fair in 1 patient. CONCLUSION The clinical efficacy of treating distal radial double-column Die-punch fractures using a dorsal approach external fixator combined with Kirschner wires is satisfactory.
Humans ; Male ; Female ; Middle Aged ; Adult ; External Fixators ; Bone Wires ; Aged ; Retrospective Studies ; Radius Fractures/physiopathology* ; Young Adult ; Fracture Fixation/methods*

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

Objective:To investigate the differential expression of Nuclear Factor Kappa B(NF-κB)and Tumor Necrosis Factor-Alpha(TNF-α)in endometrial polyp tissues,polyp-adjacent endometrium,and normal endometrium,and to analyze their correlation with local inflammatory responses,thereby elucidating the pathogenesis of endometrial polyps.Methods:Thirty-six patients with hysteroscopically confirmed endometrial polyps at Qingdao University Affiliated Hospital(September 2023-December 2024)were enrolled.Polyp tissues and adjacent endometrial tissues(0.5 cm-1 cm from polyps)were collected during surgery.Twenty-six patients undergoing hysterectomy for uterine fibroids,with pathologically confirmed normal endometrium,served as controls.The expression of NF-κB and TNF-α proteins was assessed using immunohistochemistry(IHC).Real-time quantitative PCR(RT-qPCR)was employed to detect the mRNA expression levels of NF-κB and TNF-α,and Western blot analysis was used to measure their protein expression.Differences among the three groups were compared.Results:Immunohistochemical analysis demonstrated:NF-κB p65 was predominantly localized to the cytoplasm and/or nucleus;TNF-α-positive expression was principally observed in the cytoplasmic compartment and/or cell membrane,manifesting as brown-yellow to brownish granules.The positive expression rate of NF-κB protein was significantly elevated in endometrial polyp tissues compared to both adjacent endometrial tissues and normal endometrial tissues(P＜0.05),whereas no statistically significant difference was observed between adjacent and normal endometrial tissues(P＞0.05).TNF-α protein expression exhibited a gradient pattern:Endometrial polyp tissues＞Adjacent endometrial tissues＞Normal endometrial tissues(with all inter-group comparisons demonstrating statistically significant differences,P＜0.05).Real-time quantitative PCR analysis revealed a significant gradient trend in the mRNA expression of NF-κB and TNF-α in endometrial polyp tissues:NF-κB mRNA:Polyp group(7.15±3.15)＞parapolyp group(4.38±2.01)＞normal group(1.03±0.30),with significant intergroup differences(all P＜0.05).TNF-α mRNA:Polyp tissue(17.66±9.25)＞parapolyp tissue(9.35±5.75)＞normal endometrium(1.16±0.58),with statistically significant differences among all groups(all P＜0.05).Western blot quantification further confirmed this trend:NF-κB protein:Expression in the polyp group(0.87±0.11)was 2.23-fold higher than in the normal group(0.39±0.02)(P=0.0007),while the parapolyp group(0.59±0.07)showed a 51％increase compared to the normal group(P=0.0435).TNF-α protein:Expression in the polyp group(1.13±0.21)was elevated by 94.8％versus the parapolyp group(0.58±0.03,P=0.0036)and by 494.7％versus the normal group(0.19±0.03,P=0.0002).One-way ANOVA indicated significant intergroup differences(F=43.56,P＜0.05).Conclusion:The TNF-α-mediated NF-κB signaling pathway is abnormally activated in endometrial polyps,exhibiting its highest expression at the polyp site.This suggests that the localized chronic inflammatory microenvironment may promote polyp formation through persistent stimulation of the NF-κB pathway.Targeted regulation of this pathway offers a novel strategy for preventing polyp recurrence.

Objective:To investigate the differential expression of Nuclear Factor Kappa B(NF-κB)and Tumor Necrosis Factor-Alpha(TNF-α)in endometrial polyp tissues,polyp-adjacent endometrium,and normal endometrium,and to analyze their correlation with local inflammatory responses,thereby elucidating the pathogenesis of endometrial polyps.Methods:Thirty-six patients with hysteroscopically confirmed endometrial polyps at Qingdao University Affiliated Hospital(September 2023-December 2024)were enrolled.Polyp tissues and adjacent endometrial tissues(0.5 cm-1 cm from polyps)were collected during surgery.Twenty-six patients undergoing hysterectomy for uterine fibroids,with pathologically confirmed normal endometrium,served as controls.The expression of NF-κB and TNF-α proteins was assessed using immunohistochemistry(IHC).Real-time quantitative PCR(RT-qPCR)was employed to detect the mRNA expression levels of NF-κB and TNF-α,and Western blot analysis was used to measure their protein expression.Differences among the three groups were compared.Results:Immunohistochemical analysis demonstrated:NF-κB p65 was predominantly localized to the cytoplasm and/or nucleus;TNF-α-positive expression was principally observed in the cytoplasmic compartment and/or cell membrane,manifesting as brown-yellow to brownish granules.The positive expression rate of NF-κB protein was significantly elevated in endometrial polyp tissues compared to both adjacent endometrial tissues and normal endometrial tissues(P＜0.05),whereas no statistically significant difference was observed between adjacent and normal endometrial tissues(P＞0.05).TNF-α protein expression exhibited a gradient pattern:Endometrial polyp tissues＞Adjacent endometrial tissues＞Normal endometrial tissues(with all inter-group comparisons demonstrating statistically significant differences,P＜0.05).Real-time quantitative PCR analysis revealed a significant gradient trend in the mRNA expression of NF-κB and TNF-α in endometrial polyp tissues:NF-κB mRNA:Polyp group(7.15±3.15)＞parapolyp group(4.38±2.01)＞normal group(1.03±0.30),with significant intergroup differences(all P＜0.05).TNF-α mRNA:Polyp tissue(17.66±9.25)＞parapolyp tissue(9.35±5.75)＞normal endometrium(1.16±0.58),with statistically significant differences among all groups(all P＜0.05).Western blot quantification further confirmed this trend:NF-κB protein:Expression in the polyp group(0.87±0.11)was 2.23-fold higher than in the normal group(0.39±0.02)(P=0.0007),while the parapolyp group(0.59±0.07)showed a 51％increase compared to the normal group(P=0.0435).TNF-α protein:Expression in the polyp group(1.13±0.21)was elevated by 94.8％versus the parapolyp group(0.58±0.03,P=0.0036)and by 494.7％versus the normal group(0.19±0.03,P=0.0002).One-way ANOVA indicated significant intergroup differences(F=43.56,P＜0.05).Conclusion:The TNF-α-mediated NF-κB signaling pathway is abnormally activated in endometrial polyps,exhibiting its highest expression at the polyp site.This suggests that the localized chronic inflammatory microenvironment may promote polyp formation through persistent stimulation of the NF-κB pathway.Targeted regulation of this pathway offers a novel strategy for preventing polyp recurrence.

AIM To explore the clinical effects of Jinfukang Oral Liquid combined with thymosin α1 on patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin.METHODS Seventy-five patients were randomly assigned into thymosin α1 group(15 cases)for 4-week administration,Jinfukang Oral Liquid group(30 cases)for 4-week administration,and combination group(30 cases)for 4-week administration.The changes in TCM clinical syndrome effects,immunity indices(CD3+T,Th,CTL,total NK,CD56dim CD16+NK,NKT,Treg,MDSC),lethality/inhibition ratios(CTL/Treg,total NK/Treg,NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC)and FACT-L scores were detected.RESULTS The Jinfukang Oral Liquid group and combination group demonstrated higher total effective rates than the thymosin α1 group(P＜0.05).After the treatment,the Jinfukang Oral Liquid group and combination group displayed increased NKT(P＜0.05)and decreased MDSC(P＜0.05),which were more obvious than those in the thymosin α1 group(P＜0.05),and higher NKT was observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group and combination group displayed increased lethality/inhibition ratios(P＜0.05),among which NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC were higher than those in the thymosin α1 group(P＜0.05),and higher CTL/MDSC,NKT/MDSC were observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group(except for physiological status,society and family status)and combination group(except for society and family status)displayed increased FACT-L scores(P＜0.05).CONCLUSION For the patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin,Jinfukang Oral Liquid single use or combined with thymosin α1 can enhance peripheral blood immune surveillance,inhibit immune escape,restore the balanced state of tumor immune responses,and improve TCM syndromes and life quality.