BACKGROUND:Differentially expressed RNA-binding proteins in the intervertebral disc plays a key role in intervertebral disc degeneration,and decreased levels of the RNA-binding protein KRT18 are associated with degenerative disc disease,but its specific role in the nucleus pulposus cells has not yet been fully determined. OBJECTIVE:To investigate the interaction of KRT18 with mRNA and long non-coding RNA on nucleus pulposus cells of the intervertebral disc and its mechanism. METHODS:Normal and degenerated nucleus pulposus cells were obtained from nucleus pulposus samples of patients undergoing interbody fusion for lumbar fracture or intervertebral disc degeneration.iRIP-seq,functional enrichment analysis,and DNA microarray analysis were performed to identify the mRNA and long non-coding RNA binding with KRT18.Subsequently,KRT18 was knocked down in nucleus pulposus cells based on the analysis results,and the expression levels of related genes were detected at the protein and RNA levels through protein immunoblotting and qRT-PCR,respectively. RESULTS AND CONCLUSION:Through iRIP-seq analysis,we identified abundant KRT18 binding sites within the GUAAUC and AGCCUC sequences,indicating that KRT18 may be involved in regulating RNA transcription,translation,stability or play a role in cell signaling pathways.It can stably bind to mature mRNA,among which highly expressed genes include CRLF1,IGFBP4,etc.At the same time,the peak genes of long non-coding RNA binding with it include SNHG25,SNHG12,NEAT1,USP32,EIF4A2 and CDH4.Most of these genes are involved in various biological processes such as apoptosis and inflammation,and can mediate related pathways of extracellular matrix metabolism.KRT18 can regulate their stability,transport,translation,splicing and other functions,thus affecting gene expression and cell function.We further verified through experiments the knockdown of KRT18 in nucleus pulposus cells,and found that the level of extracellular matrix metabolism was inhibited and unbalanced,resulting in intervertebral disc degeneration in vitro.This study investigated the regulatory mechanism of KRT18 from the perspective of its binding with mRNA and long non-coding RNA for the first time,and speculated the potential function of KRT18 in the pathogenesis of intervertebral disc degeneration,laying a foundation for future research on the key functions of KRT18.

BACKGROUND:A novel aggregation induced luminescence fluorescence probe based on the mechanism of intramolecular motility restriction can be used for the detection of disease markers,tumor diagnosis,and bacterial imaging recognition.OBJECTIVE:To prepare a near-infrared Ⅱ nanoprobe called FA-DSPE-PEG-AIE@NPs based on aggregation-induced luminescence,and to explore its potential of targeted fluorescence imaging and photothermal therapy for prostate cancer.METHODS:Lecithin,polyethylene glycol phospholipids,folate polyethylene glycol phospholipids,and aggregation induced luminescent molecule 2TT-oC26B were used as raw materials.The folate-targeted nanoprobe FA-DSPE-PEG-AIE@NPs were prepared by nanoprecipitation method,and basic characterization of the nanoprobe was detected.PC3 human prostate cancer cells and human umbilical vein endothelial cells were selected as experimental objects.The cytotoxicity and phototoxicity of FA-DSPE-PEG-AIE@NPs were detected.PC3 human prostate cancer cells were selected as the experimental objects.Flow cytometry and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.PC3 human prostate cancer cells were injected subcutaneously into the abdomen of BALB/C nude mice to establish a tumor model,and nanoprobes FA-DSPE-PEG-AIE@NPs were injected into the tail vein.The mice were immediately subjected to near-infraced Ⅱ fluorescence imaging.12 hours later,the tumor was irradiated by laser for 5 minutes,and the photothermal treatment effect was observed within 14 days.RESULTS AND CONCLUSION:(1)The nanoprobes FA-DSPE-PEG-AIE@NPs with a mean diameter of(171.0±0.3)nm showed a well-defined spherical morphology.The nanoprobe had a wide absorption spectrum and tail emission extending to the near-infrared Ⅱ which emitted a bright near-infrared Ⅱ fluorescence signal under laser irradiation.(2)The nanoprobes FA-DSPE-PEG-AIE@NPs had low cytotoxicity and high phototoxicity.The results of flow cytometry and calcein/propidium iodide staining showed that nanoprobes FA-DSPE-PEG-AIE@NPs had an obvious photothermal killing effect on human prostate cancer cells.(3)The nanoprobes FA-DSPE-PEG-AIE@NPs successfully achieved near-infrared Ⅱ fluorescence imaging of mouse blood vessels and the maximum enrichment time of the tumor was 12 hours.The vessel widths of the hind leg and single blood vessels of abdomen were estimated to be 0.63 mm and 0.42 mm.The tumor volume of mice was significantly smaller after 14 days of treatment.(4)The results show that nanoprobes FA-DSPE-PEG-AIE@NPs can achieve near-infrared Ⅱ fluorescence imaging and photothermal therapy of prostate cancer effectively,which may provide a new method for early diagnosis and combined treatment of prostate cancer.

Objective:To compare the efficacy and safety of LY01011,a recombinant anti-RANKL fully human monoclonal antibody injection,versus denosumab in the treatment of bone metastases from solid tumors.Methods:A randomized,double-blind,positive drug parallel-controlled,multicenter clinical trial was conducted.A total of 850 subjects were randomly assigned(1:1)to either the experimental group(424 subjects)or the control group(426 subjects).The experimental group received 13 doses of LY01011,while the control group received 3 doses of denosumab followed by 10 doses of LY01011.Results:The primary efficacy endpoint was the natural logarithmic change from baseline in urinary N-terminal telopeptide of type I collagen corrected by urinary creatinine(uNTX/uCr)at week 13.The change was-1.740(0.042 0)in the experimental group and-1.745(0.042 1)in the control group.The least-squares mean difference between groups was 0.005(90%CI:-0.088 to 0.097),indicating no statistically significant difference(P>0.05).Safety profiles,including treatment-emergent adverse events,laboratory tests,vital signs,physical examinations,and electrocardiograms,were comparable between groups(P>0.05).Conclusions:LY01011 demonstrated biosimilarity to denosumab,with favorable safety profile,tolerability,and potential for clinical application.

Objective To conduct a cross-sectional study on the relationship between the serum uric acid(sUA)to high density lipoprotein-cholesterol(HDL-C)ratio(UHR)and female infertility.Methods We analyzed data from the National Health and Nutrition Examination Survey(NHANES)2013-2018 cycle,examining 2,963 women aged 18 to 45 years.A multivariable Logistic regression model was used to assess the association between UHR and infertility,adjusting for various confounding factors.The study also explored interactions and dose-response relationships through subgroup analyses and restricted cubic spline(RCS)models,and evaluated the predictive value of UHR for infertility by using receiver operating characteristic(ROC)curve analysis.Results The results showed that the prevalence of infertility was significantly higher among women with elevated UHR.Baseline characteristics revealed that the mean UHR in women with infertility(9.68±4.23)was significantly higher than in those without infertility(8.7±3.81,P<0.001).Multivariable Logistic regression analysis indicated that women in the highest quartile(Q4)of UHR had a significantly increased likelihood of infertility compared to those in the lowest quartile(Q1),with adjusted odds ratios(ORs)ranging from 1.61(95% CI:1.14-2.28)to 1.98(95% CI:1.42-2.78)across different models(P for trend<0.001).Subgroup analyses demonstrated that these associations were consistent across different age groups,body mass index(BMI)categories,and racial groups.The RCS model showed a significant linear dose-response relationship between UHR and infertility risk(nonlinear P=0.03,overall association P<0.001).Additionally,ROC analysis indicated that UHR had a moderate ability to discriminate infertility status,with an area under the curve(AUC)of 0.570.Conclusion A higher UHR is significantly associated with an increased risk of female infertility,and UHR has the potential to serve as a predictive biomarker for the risk of female infertility.

Objective This study aims to develop a guideline for assessing and maintaining intrinsic capacity in older adults,offer recommendations to professionals regarding these assessments,and encourage the implementation of evidence-based clinical practices across various settings,including communities,hospitals,nursing homes,and other geriatric care environments.Methods An evidence-based approach guided the collection of questions through a lit-erature review.Preliminary recommendations were developed through a systematic search of domestic and interna-tional guideline networks,professional association websites,and comprehensive databases.Subsequently,the recom-mendations were revised,and the consensus was achieved through a round of expert consensus meetings and 3 rounds of expert correspondence,culminating in the formation of the guidelines.Results The developed guideline encompasses 2 aspects and 5 dimensions of assessment and maintenance,comprising a total of 28 questions and 39 recommendations.Specifically,6 questions and 9 recommendations were formulated for the cognitive dimension,5 questions and 7 recommendations for the locomotion dimension,6 questions and 7 recommendations for the vitality dimension,6 questions and 9 recommendations for the psychological dimension,and 5 questions and 7 recommenda-tions for the sensory dimension.Among these,34 are classified as strong recommendations,while 5 are categorized as weak recommendations.Conclusion The guideline offers scientifically robust,acceptable,and comprehensible rec-ommendations that equip the professionals with a foundation for decision-making aiming at preserving the intrinsic capacity of older adults.

ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop （TTFL） of biorhythm in the rat model of non-alcoholic fatty liver disease （NAFLD） and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank （n=20）， model （n=15）， and low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） modified Ditan tang （n=10） groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage， and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid （NEFA） assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining， and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 （BMAL1/ARNTL） in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1， circadian locomotor output cycles kaput （CLOCK）， period circadian clock 2 （PER2）， and cryptochrome1 （Cry1） in the hypothalamus and liver were determined by Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed elevated levels of TG， TC， LDL-C， AST， and ALT （P<0.01） and a lowered level of HDL-C （P<0.05） in the serum， elevated levels of TG and NEFA in the liver （P<0.01）， pyknosis and deep staining of hypothalamic neuron cells， and a large number of vacuoles in the brain area. In addition， the model group showed lipid deposition in the liver， up-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.01）， and down-regulated mRNA and protein levels of Cry1 and PER2 （P<0.01） in the hypothalamus and liver. Compared with the model group， all the three modified Ditan tang groups showed lowered levels of TG， TC， LDL-C， ALT， and AST （P<0.05， P<0.01） and an elevated level of HDL-C （P<0.05） in the serum， and lowered levels of TG and NEFA （P<0.05， P<0.01） in the liver. Furthermore， the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells， reduced lipid deposition in the liver， down-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.05， P<0.01）， and up-regulated mRNA and protein levels of Cry1 and PER2 （P<0.05， P<0.01） in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK， BMAL1， Cry1， and PER2 in the TTFL of NAFLD rats.

Viruses,with high adaptability and immune evasion capabilities,are responsible for a wide spectrum of diseases from lo-calized infections to global pandemics,continuously posing threats to global public health.In recent years,traditional Chinese medi-cine(TCM)has demonstrated significant potential in antiviral therapy.With its multi-component,multi-target synergistic mechanism,TCM offers unique advantages in the intervention of viral diseases.However,progress in elucidating the active antiviral constituents of TCM and identifying their precise molecular targets remains limited,primarily due to the lack of humanized models that can faithfully recapitulate the natural course of viral infection.The emergence of organoid technology has introduced new opportunities for antiviral research in TCM.Human organoids,which recapitulate the three-dimensional architecture and physiological functions of human tis-sues,provide an advanced platform for modeling host-virus interactions in a human-relevant context.This article highlights the latest advances in applications of human tissue organoids,including lung,liver,and brain organoids,in the study of respiratory viruses(SARS-CoV-2,influenza virus,respiratory syncytial virus),hepatitis viruses(HBV,HCV,HEV),and neurotropic viruses(ZIKV,pri-ons,HCMV);illustrates how organoid models have been leveraged to evaluate both the efficacy and safety of TCM-based antiviral inter-ventions.Although human tissue organoids still face technical challenges in insufficient vascularization and incomplete immune micro-environment,they represent a powerful tool for dissecting the mechanism of TCM antiviral action and for guiding the development of personalized antiviral strategies.Looking ahead,human tissue organoid technology is expected to become key enabling platform for pro-moting the clinical transformation of TCM in the field of antiviral medicine.

Objective To evaluate the diagnostic concordance rates between zonal localization and diffusion weighted imaging(DWI)localization of prostate cancer,and to investigate the diagnostic efficacy of DWI for prostate cancer in the transition zone and peripheral zone.Methods Patients with localized prostate cancer who underwent radical prostatectomy were selected.5-grade Lik-ert-scale was used to determine the suspicion level of prostate cancer in DWI sequnence.Patients were divided into no suspicious lesion group(91 cases)(grade≤2 points)and suspicious lesion group(194 cases)(grade≥3 points).The t test,Mann-Whitney U test and χ2 test were used to compare the clinicopathological features between the two groups.Multiple regression analysis was used to detect the correlation between DWI grading and pathological features in the suspicious lesion group.Patients were also divided into transition zone and peripheral zone groups according to zonal localization of lesions.The diagnostic concordance rates between DWI image localization and zonal localization in the suspicious lesion group were compared by χ2 test.Results The study included 285 prostate cancer patients,the prostate-specific antigen(PSA),Gleason score,clinical/pathological stages,tumor volume and extracapsular extension of the sus-picious lesion group were higher than those of the no suspicious lesion group with significant differences(P<0.05).Multiple regres-sion test results showed significant positive correlations between DWI grading and pathological features,including pathological Glea-son score,pathological stages,tumor volume and extracapsular extension(P<0.05).The diagnostic concordance rates of DWI for prostate cancer in different zonal origins increased with the increase of DWI grading.The diagnostic concordance rates of peripheral zone group were higher than those of transition zone group,with more significant differences showed in DWI grade>3 points(P<0.05).Conclusion Prostate cancer with higher DWI grading may have more aggressive clinicopathological features,and show a better diag-nostic concordance rate than those with lower DWI grading.In addition,the diagnostic concordance rate of peripheral zone prostate cancer is higher than that of transition zone prostate cancer,with significant differences in higher DWI grading.

Objective This study aims to develop a guideline for assessing and maintaining intrinsic capacity in older adults,offer recommendations to professionals regarding these assessments,and encourage the implementation of evidence-based clinical practices across various settings,including communities,hospitals,nursing homes,and other geriatric care environments.Methods An evidence-based approach guided the collection of questions through a lit-erature review.Preliminary recommendations were developed through a systematic search of domestic and interna-tional guideline networks,professional association websites,and comprehensive databases.Subsequently,the recom-mendations were revised,and the consensus was achieved through a round of expert consensus meetings and 3 rounds of expert correspondence,culminating in the formation of the guidelines.Results The developed guideline encompasses 2 aspects and 5 dimensions of assessment and maintenance,comprising a total of 28 questions and 39 recommendations.Specifically,6 questions and 9 recommendations were formulated for the cognitive dimension,5 questions and 7 recommendations for the locomotion dimension,6 questions and 7 recommendations for the vitality dimension,6 questions and 9 recommendations for the psychological dimension,and 5 questions and 7 recommenda-tions for the sensory dimension.Among these,34 are classified as strong recommendations,while 5 are categorized as weak recommendations.Conclusion The guideline offers scientifically robust,acceptable,and comprehensible rec-ommendations that equip the professionals with a foundation for decision-making aiming at preserving the intrinsic capacity of older adults.

Objective To evaluate the diagnostic concordance rates between zonal localization and diffusion weighted imaging(DWI)localization of prostate cancer,and to investigate the diagnostic efficacy of DWI for prostate cancer in the transition zone and peripheral zone.Methods Patients with localized prostate cancer who underwent radical prostatectomy were selected.5-grade Lik-ert-scale was used to determine the suspicion level of prostate cancer in DWI sequnence.Patients were divided into no suspicious lesion group(91 cases)(grade≤2 points)and suspicious lesion group(194 cases)(grade≥3 points).The t test,Mann-Whitney U test and χ2 test were used to compare the clinicopathological features between the two groups.Multiple regression analysis was used to detect the correlation between DWI grading and pathological features in the suspicious lesion group.Patients were also divided into transition zone and peripheral zone groups according to zonal localization of lesions.The diagnostic concordance rates between DWI image localization and zonal localization in the suspicious lesion group were compared by χ2 test.Results The study included 285 prostate cancer patients,the prostate-specific antigen(PSA),Gleason score,clinical/pathological stages,tumor volume and extracapsular extension of the sus-picious lesion group were higher than those of the no suspicious lesion group with significant differences(P<0.05).Multiple regres-sion test results showed significant positive correlations between DWI grading and pathological features,including pathological Glea-son score,pathological stages,tumor volume and extracapsular extension(P<0.05).The diagnostic concordance rates of DWI for prostate cancer in different zonal origins increased with the increase of DWI grading.The diagnostic concordance rates of peripheral zone group were higher than those of transition zone group,with more significant differences showed in DWI grade>3 points(P<0.05).Conclusion Prostate cancer with higher DWI grading may have more aggressive clinicopathological features,and show a better diag-nostic concordance rate than those with lower DWI grading.In addition,the diagnostic concordance rate of peripheral zone prostate cancer is higher than that of transition zone prostate cancer,with significant differences in higher DWI grading.