The level of urinary albumin is a critical indicator for the early diagnosis and management of chronic kidney disease (CKD). However, existing methods for detecting albumin are not conducive to point-of-care testing due to the complexity of reagent addition and incubation processes. This study presents a smartphone-integrated handheld automated biochemical analyzer (sHABA) designed for point-of-care testing of urinary albumin. The sHABA features a pre-loaded, disposable reagent cassette with reagents for the albumin assay arranged in the order of their addition within a hose. The smartphone-integrated analyzer can drive the reagents following a preset program, to enable automatic sequential addition. The sHABA has a detection limit for albumin of 5.9 mg/L and a linear detection range from 7 to 450 mg/L. The consistency of albumin level detection in 931 urine samples using sHABA with clinical tests indicates good sensitivity (95.78%) and specificity (90.16%). This research advances the field by providing an automated detection method for albumin in a portable device, allowing even untrained individuals to monitor CKD in real time at the patient's bedside. In the context of promoting tiered diagnosis and treatment, the sHABA has the potential to become an essential tool for the early diagnosis and comprehensive management of CKD and other chronic conditions.

The level of urinary albumin is a critical indicator for the early diagnosis and management of chronic kidney disease(CKD).However,existing methods for detecting albumin are not conducive to point-of-care testing due to the complexity of reagent addition and incubation processes.This study presents a smartphone-integrated handheld automated biochemical analyzer(sHABA)designed for point-of-care testing of urinary albumin.The sHABA features a pre-loaded,disposable reagent cassette with re-agents for the albumin assay arranged in the order of their addition within a hose.The smartphone-integrated analyzer can drive the reagents following a preset program,to enable automatic sequential addition.The sHABA has a detection limit for albumin of 5.9 mg/L and a linear detection range from 7 to 450 mg/L.The consistency of albumin level detection in 931 urine samples using sHABA with clinical tests indicates good sensitivity(95.78％)and specificity(90.16％).This research advances the field by providing an automated detection method for albumin in a portable device,allowing even untrained individuals to monitor CKD in real time at the patient's bedside.In the context of promoting tiered diagnosis and treatment,the sHABA has the potential to become an essential tool for the early diagnosis and comprehensive management of CKD and other chronic conditions.

Objective:To analyze the differences between subjective refraction and autorefraction in myopic children and adolescents under different ciliary muscle functional states.Methods:A cohort study was conducted.A total of 98 myopic children and adolescents (196 eyes) aged 7-15 years who visited the Shanghai Eye Disease Prevention and Treatment Center from November 2023 to February 2024 were included by random sampling.All participants underwent cycloplegia with 1.0% cyclopentolate and completed both subjective refraction and autorefraction before cycloplegia, after cycloplegia and after recovery from cycloplegia.The spherical equivalent (SE) differences and differences in SE(ΔSE) between different conditions were compared.Proportion of ΔSE, differences in spherical power (ΔS), and differences in cylindrical power (ΔC) of objective and subjective refraction between different conditions within the clinically acceptable error range (-0.25 to 0.25 D) was calculated and compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shanghai Eye Diseases Prevention & Treatment Center (No.2021SQ021).Written informed consent was obtained from guardian of each subject before any medical examination.Results:The SE values obtained from autorefraction before cycloplegia, after cycloplegia, and after recovery from cycloplegia were -2.44(-3.47, -1.63), -2.13(-3.25, -1.50), and -2.38(-3.50, -1.66)D, respectively, with a statistically significant overall difference ( χ2=148.36, P<0.001) and statistically significant differences in pairwise comparisons at different time points (all P<0.001); for subjective refraction, the SE values were -2.25(-3.50, -1.50), -2.19(-3.47, -1.45), and -2.28(-3.50, -1.50)D, respectively, with a statistically significant overall difference ( χ2=43.48, P<0.001) and statistically significant differences in pairwise comparisons at different time points (all P<0.001).Subjective refraction ΔSE between before and after cycloplegia, after cycloplegia and after recovery from cycloplegia were significantly smaller than those of autorefraction ( t=2.84, 1.82; both P<0.001).There was no significant difference in ΔSE between subjective refraction and autorefraction between before cycloplegia and after recovery from cycloplegia ( t=-0.43, P=0.070).The proportions of subjective refraction ΔSE within the acceptable error range between before and after cycloplegia, before cycloplegia and after recovery from cycloplegia, and after cycloplegia and after recovery from cycloplegia were significantly higher than those of autorefraction ( χ2=28.32, 11.82, 25.55; all P<0.001).The proportion of subjective refraction ΔS and ΔC both within the acceptable error range between before cycloplegia and after recovery from cycloplegia was 81.63%(160/196) and 79.59%(156/196) between after cycloplegia and after recovery from cycloplegia. Conclusions:Subjective refraction is less affected by different ciliary muscle functional states.The differences in subjective refraction results under different ciliary muscle functional states are mostly within the acceptable error range.The subjective refraction results before or after cycloplegia can be used to better predict the subjective refraction results after recovery from cycloplegia.

Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans ; Peptides/therapeutic use* ; Structure-Activity Relationship ; Functional Food ; Diabetes Mellitus, Type 2/drug therapy* ; Biological Availability ; Alzheimer Disease/drug therapy* ; Inflammatory Bowel Diseases/drug therapy* ; Hypertension/drug therapy* ; Liver Diseases/drug therapy* ; Bioactive Peptides, Dietary

Objective:To analyze the differences between subjective refraction and autorefraction in myopic children and adolescents under different ciliary muscle functional states.Methods:A cohort study was conducted.A total of 98 myopic children and adolescents (196 eyes) aged 7-15 years who visited the Shanghai Eye Disease Prevention and Treatment Center from November 2023 to February 2024 were included by random sampling.All participants underwent cycloplegia with 1.0% cyclopentolate and completed both subjective refraction and autorefraction before cycloplegia, after cycloplegia and after recovery from cycloplegia.The spherical equivalent (SE) differences and differences in SE(ΔSE) between different conditions were compared.Proportion of ΔSE, differences in spherical power (ΔS), and differences in cylindrical power (ΔC) of objective and subjective refraction between different conditions within the clinically acceptable error range (-0.25 to 0.25 D) was calculated and compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shanghai Eye Diseases Prevention & Treatment Center (No.2021SQ021).Written informed consent was obtained from guardian of each subject before any medical examination.Results:The SE values obtained from autorefraction before cycloplegia, after cycloplegia, and after recovery from cycloplegia were -2.44(-3.47, -1.63), -2.13(-3.25, -1.50), and -2.38(-3.50, -1.66)D, respectively, with a statistically significant overall difference ( χ2=148.36, P<0.001) and statistically significant differences in pairwise comparisons at different time points (all P<0.001); for subjective refraction, the SE values were -2.25(-3.50, -1.50), -2.19(-3.47, -1.45), and -2.28(-3.50, -1.50)D, respectively, with a statistically significant overall difference ( χ2=43.48, P<0.001) and statistically significant differences in pairwise comparisons at different time points (all P<0.001).Subjective refraction ΔSE between before and after cycloplegia, after cycloplegia and after recovery from cycloplegia were significantly smaller than those of autorefraction ( t=2.84, 1.82; both P<0.001).There was no significant difference in ΔSE between subjective refraction and autorefraction between before cycloplegia and after recovery from cycloplegia ( t=-0.43, P=0.070).The proportions of subjective refraction ΔSE within the acceptable error range between before and after cycloplegia, before cycloplegia and after recovery from cycloplegia, and after cycloplegia and after recovery from cycloplegia were significantly higher than those of autorefraction ( χ2=28.32, 11.82, 25.55; all P<0.001).The proportion of subjective refraction ΔS and ΔC both within the acceptable error range between before cycloplegia and after recovery from cycloplegia was 81.63%(160/196) and 79.59%(156/196) between after cycloplegia and after recovery from cycloplegia. Conclusions:Subjective refraction is less affected by different ciliary muscle functional states.The differences in subjective refraction results under different ciliary muscle functional states are mostly within the acceptable error range.The subjective refraction results before or after cycloplegia can be used to better predict the subjective refraction results after recovery from cycloplegia.

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

OBJECTIVES: In light of the rise in the global aging population, this study investigated the potential of the oxidative balance score (OBS) as an indicator of phenotypic age acceleration (PhenoAgeAccel) to better understand and potentially slow down aging. METHODS: Utilizing data from the National Health and Nutrition Examination Survey collected between 2001 and 2010, including 13,142 United States adults (48.7% female and 51.2% male) aged 20 and above, OBS and PhenoAgeAccel were calculated. Weighted generalized linear regression models were employed to explore the associations between OBS and PhenoAgeAccel, including a sex-specific analysis. RESULTS: The OBS demonstrated significant variability across various demographic and health-related factors. There was a clear negative correlation observed between the higher OBS quartiles and PhenoAgeAccel, which presented sex-specific results: the negative association between OBS and PhenoAgeAccel was more pronounced in male than in female. An analysis using restricted cubic splines revealed no significant non-linear relationships. Interaction effects were noted solely in the context of sex and hyperlipidemia. CONCLUSIONS A higher OBS was significantly associated with a slower aging process, as measured by lower PhenoAgeAccel. These findings underscore the importance of OBS as a biomarker in the study of aging and point to sex and hyperlipidemia as variables that may affect this association. Additional research is required to confirm these results and to investigate the biological underpinnings of this relationship.

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Objective:Based on targeted amplicon technology combined with high-throughput sequencing technology and bioinformatic analysis technology, to understand the characteristics of the whole genome of the monkeypox virus and its variation, and to construct a method for the analysis of monkeypox virus variation and molecular traceability of the case in Qinghai province, and to provide technical support for the prevention and control of monkeypox epidemic in the future.Methods:The extracted viral DNA was used as a template, and the genome of monkeypox virus was specifically amplified by Ion AmpliSeq Monkeypox Panel with the number of amplicons 1 609 and the length of 125 bp-275 bp, and the sequencing library was constructed by Ion AmpliSeq Library Kit Plus, and sequenced by Ion Torrent GeneStudio S5. The sequencing library was constructed by Ion AmpliSeq Library Kit Plus, and the monkeypox virus genome was sequenced using Ion Torrent GeneStudio S5 sequencer. Monkeypox virus was analyzed for genomic profiling and mutation site analysis using the online analysis tool Nextclade. The genomic sequence of the case virus in this study was compared with some sequences in the GIASID monkeypox virus database and a phylogenetic tree was constructed to analyze the potential origin of the case virus.Results:The Ct values of monkeypox virus genes in the rash swab and oropharyngeal swab samples were 32.13 and 36.91, respectively. The rash swab sample had a reads number match of 99.99% and a genome coverage of 99.45% after whole-genome sequencing of monkeypox virus, and the sequences belonged to the IIb (West African branch) B. 1.3 type. The analysis of nucleotide mutation sites and phylogenetic tree showed that the sequences were in the same branch with four monkeypox virus genome sequences recently submitted by China and Japan in the GISAID monkeypox virus database, and had the closest evolutionary relationship with the sequence EPI_ISL_18059184 (sampled on 2023-07-03) submitted by Yunnan, China, which shared 82 single-nucleotide mutation sites, among which the sequence from Yunnan was only present in all of the shared 82 single-nucleotide mutation sites. The sequence in this study has 2 additional nucleotide mutation sites on top of the shared 82 single nucleotide mutation sites. The sequence submitted by Japan, EPI_ISL_17692269 (sampled on 2023-04-28), is more closely related in evolution, sharing 78 single nucleotide mutation sites, with 7 single nucleotide mutation site differences, and the Japanese sequence shares 78 single nucleotide mutation sites. The Japanese sequence shared 78 mutation sites with one additional nucleotide mutation site (G57786A), while the present sequence had six additional nucleotide mutation sites (G13563A, C21062T, G101241A, C142797T, G152866A, T169721A).Conclusions:The whole genome sequence of monkeypox virus of 197 084 bp was successfully obtained from a sample with low viral load, and the average. We constructed a method for sequencing and analyzing the whole genome of monkeypox virus.

The crosstalk between the nerve and stomatognathic systems plays a more important role in organismal health than previously appreciated with the presence of emerging concept of the "brain-oral axis". A deeper understanding of the intricate interaction between the nervous system and the stomatognathic system is warranted, considering their significant developmental homology and anatomical proximity, and the more complex innervation of the jawbone compared to other skeletons. In this review, we provide an in-depth look at studies concerning neurodevelopment, craniofacial development, and congenital anomalies that occur when the two systems develop abnormally. It summarizes the cross-regulation between nerves and jawbones and the effects of various states of the jawbone on intrabony nerve distribution. Diseases closely related to both the nervous system and the stomatognathic system are divided into craniofacial diseases caused by neurological illnesses, and neurological diseases caused by an aberrant stomatognathic system. The two-way relationships between common diseases, such as periodontitis and neurodegenerative disorders, and depression and oral diseases were also discussed. This review provides valuable insights into novel strategies for neuro-skeletal tissue engineering and early prevention and treatment of orofacial and neurological diseases.
Bone and Bones ; Nervous System ; Stomatognathic System ; Humans