p21 (encoded by the CDKN1A gene) is a critical cell cycle regulatory protein endowed with versatile biological functions. In various sex hormone-related cancers, p21 exhibits a paradoxical dual role, capable of both inhibiting tumorigenesis and promoting cancer progression, exerting dual, often opposing, effects on cellular fate that are dictated by the specific context. The clinical targeting of p21 remains elusive, largely due to its functionally pleiotropic and context-dependent nature within intricate regulatory networks. During the initial, hormone-dependent phase of cancers like breast and prostate cancer, p21 expression and activity are largely governed by the transcriptional programs of estrogen or androgen receptor signaling. This hormonal regulation contributes to the control of tumor cell proliferation and underpins the initial efficacy of endocrine therapies. In contrast, as these diseases advance to late stages or evolve into non-hormone-dependent subtypes—exemplified by castration-resistant prostate cancer (CRPC) and specific forms of triple-negative breast cancer (TNBC)—these conventional hormonal control mechanisms often become dysfunctional or are entirely bypassed. This fundamental transition creates a critical therapeutic void, highlighting the urgent need to identify and exploit alternative molecular pathways to effectively target p21’s function. Promising strategies may include the precise modulation of its upstream transcriptional regulators, downstream effector proteins, or the intersecting parallel signaling networks that critically influence its activity. This review provides a systematic synthesis of the intricate and interconnected mechanisms that underpin the dual effects of p21 in sex hormone-related tumors. These mechanisms are categorized into three core, interrelated functional domains. (1) cell cycle regulation: p21 executes its canonical tumor-suppressive role by binding to and inhibiting cyclin-dependent kinases (CDKs) and by directly interacting with proliferating cell nuclear antigen (PCNA), thereby inducing cell cycle arrest, predominantly at the G1/S checkpoint; (2) apoptosis modulation: p21 exerts a highly context-dependent influence on programmed cell death, functioning either as a pro-apoptotic agent under severe genotoxic stress or as a pro-survival factor by inhibiting apoptosis through interactions with proteins like Bcl-2; (3) hormonal and signaling crosstalk: p21 is an integral node within broader cellular networks, engaging in direct physical interactions with hormone receptors(e.g., AR, ER) and participating in complex feedback loops with key oncogenic pathways, including PI3K/AKT, MAPK/ERK, and p53. Critically, the role of p21 is not static but highly dynamic. It can undergo a functional switch from tumor-suppressive to tumor-promoting in response to therapeutic pressures, metabolic alterations, or evolving tumor microenvironment cues. These adaptive shifts are frequently implicated in the development of therapy resistance and disease recurrence, particularly in advanced, hormone-resistant cancers. By synthesizing these insights, this review aims to establish a coherent theoretical framework to guide the future development of novel therapeutic strategies that target the p21 pathway. It underscores the necessity of moving beyond a simplistic, binary view of p21 and emphasizes the forthcoming challenges, such as the discovery of reliable biomarkers to predict its functional state and the rational design of context-specific pharmacological modulators to selectively harness its therapeutic potential.

ObjectiveIn traditional Chinese medicine (TCM), the foundational doctrine that the eyes reflect the essence of the internal viscera establishes ocular observation as a cornerstone of diagnostic practice. Specifically, the morphological characteristics and coloration variations of the scleral microvasculature serve as critical clinical indicators for assessing the dynamic balance of Qi and Blood, as well as the pathological status of internal organs. Historically, however, TCM eye diagnosis has relied predominantly on the subjective clinical experience and visual acuity of individual practitioners, leading to inherent challenges in standardization and reproducibility. While automated computer-aided diagnostic systems offer a promising solution, existing vessel segmentation algorithms encounter significant domain-specific bottlenecks when applied to scleral imagery. These challenges primarily stem from the highly reflective and moist nature of the ocular surface, which generates severe reflective interference. Furthermore, the inherent low contrast of fine capillary networks against complex background textures, compounded by non-uniform illumination, frequently results in high false-positive rates, misdetections, and severe vessel fragmentation. To address these critical limitations and advance the objective quantification of TCM diagnostics, this paper proposes a novel, highly robust sclera vessel segmentation framework that innovatively integrates Frangi-Sato dual-filter adaptive enhancement with pixel-level reflection detection. MethodsThe proposed methodology systematically addresses the segmentation pipeline through three synergistic stages. First, to overcome the structural limitations of single-filter approaches, a multi-scale weighted fusion strategy is meticulously designed to harness the complementary extraction capabilities of both Frangi and Sato filters. This adaptive enhancement optimally balances the preservation of main vessel trunk continuity with the heightened sensitivity required for delineating delicate, low-contrast peripheral capillaries. Second, to tackle the persistent issue of reflective highlights, a sophisticated multi-feature synergistic reflection detection module is introduced. By jointly analyzing local information entropy, gradient field variations, and intensity statistical distributions, this module achieves precise, pixel-level identification and elimination of reflective artifacts without compromising the underlying vascular structures. Finally, a dual-level adaptive thresholding strategy, featuring an innovative “core protection” mechanism, is implemented. This critical step effectively suppresses complex background noise while rigorously preserving the structural and topological integrity of the intricate vessel network, preventing the structural breaks often seen in conventional binarization methods. ResultsThe efficacy of the proposed framework was rigorously evaluated using both self-constructed clinical datasets specifically acquired for TCM research and standardized public datasets. Extensive experimental results demonstrate that the proposed method consistently outperforms state-of-the-art traditional approaches and contemporary deep learning models. Specifically, the proposed method achieves a Dice similarity coefficient of approximately 0.71 on the private clinical dataset, and secures the best performance across the majority of quantitative metrics on both datasets. Notably, the framework exhibits exceptional robustness and generalization capabilities in highly challenging scenarios characterized by intense reflective interference, low signal-to-noise ratios, and cross-domain image variations. ConclusionThis study successfully realizes the high-integrity, automated segmentation of scleral vessel networks under complex clinical imaging conditions. By overcoming the fundamental algorithmic challenges of reflection interference and micro-vessel loss, the proposed methodology provides potential support for the digitization, objective standardization, and intelligent advancement of modern TCM eye diagnosis systems.

ObjectiveIn traditional Chinese medicine (TCM), the foundational doctrine that the eyes reflect the essence of the internal viscera establishes ocular observation as a cornerstone of diagnostic practice. Specifically, the morphological characteristics and coloration variations of the scleral microvasculature serve as critical clinical indicators for assessing the dynamic balance of Qi and Blood, as well as the pathological status of internal organs. Historically, however, TCM eye diagnosis has relied predominantly on the subjective clinical experience and visual acuity of individual practitioners, leading to inherent challenges in standardization and reproducibility. While automated computer-aided diagnostic systems offer a promising solution, existing vessel segmentation algorithms encounter significant domain-specific bottlenecks when applied to scleral imagery. These challenges primarily stem from the highly reflective and moist nature of the ocular surface, which generates severe reflective interference. Furthermore, the inherent low contrast of fine capillary networks against complex background textures, compounded by non-uniform illumination, frequently results in high false-positive rates, misdetections, and severe vessel fragmentation. To address these critical limitations and advance the objective quantification of TCM diagnostics, this paper proposes a novel, highly robust sclera vessel segmentation framework that innovatively integrates Frangi-Sato dual-filter adaptive enhancement with pixel-level reflection detection. MethodsThe proposed methodology systematically addresses the segmentation pipeline through three synergistic stages. First, to overcome the structural limitations of single-filter approaches, a multi-scale weighted fusion strategy is meticulously designed to harness the complementary extraction capabilities of both Frangi and Sato filters. This adaptive enhancement optimally balances the preservation of main vessel trunk continuity with the heightened sensitivity required for delineating delicate, low-contrast peripheral capillaries. Second, to tackle the persistent issue of reflective highlights, a sophisticated multi-feature synergistic reflection detection module is introduced. By jointly analyzing local information entropy, gradient field variations, and intensity statistical distributions, this module achieves precise, pixel-level identification and elimination of reflective artifacts without compromising the underlying vascular structures. Finally, a dual-level adaptive thresholding strategy, featuring an innovative “core protection” mechanism, is implemented. This critical step effectively suppresses complex background noise while rigorously preserving the structural and topological integrity of the intricate vessel network, preventing the structural breaks often seen in conventional binarization methods. ResultsThe efficacy of the proposed framework was rigorously evaluated using both self-constructed clinical datasets specifically acquired for TCM research and standardized public datasets. Extensive experimental results demonstrate that the proposed method consistently outperforms state-of-the-art traditional approaches and contemporary deep learning models. Specifically, the proposed method achieves a Dice similarity coefficient of approximately 0.71 on the private clinical dataset, and secures the best performance across the majority of quantitative metrics on both datasets. Notably, the framework exhibits exceptional robustness and generalization capabilities in highly challenging scenarios characterized by intense reflective interference, low signal-to-noise ratios, and cross-domain image variations. ConclusionThis study successfully realizes the high-integrity, automated segmentation of scleral vessel networks under complex clinical imaging conditions. By overcoming the fundamental algorithmic challenges of reflection interference and micro-vessel loss, the proposed methodology provides potential support for the digitization, objective standardization, and intelligent advancement of modern TCM eye diagnosis systems.

Objective:To explore the alterations in gray matter morphology and contributing factors in patients with post-infectious olfactory dysfunction (PIOD) using voxel-based morphometry (VBM) and surface-based morphometry (SBM), thereby providing scientific insights into the neuropathological mechanisms underlying PIOD.Methods:A total of 46 PIOD patients (PIOD group) and 46 normosmic volunteers (control group) were recruited from the Smell and Taste Disorders Clinic of Beijing Anzhen Hospital, Capital Medical University, between January 2020 and December 2024. All participants underwent olfactory psychophysical tests (Sniffin′ Sticks) and olfactory event-related potential (oERP) examination. High-resolution T1-weighted 3D MRI structural images were obtained for both groups. VBM was employed to analyze inter-group differences in gray matter volume, while SBM was used to assess cortical thickness and folding index. Correlations between gray matter volume in significant difference brain regions and disease duration, Sniffin′ Sticks scores, oERP parameters were analyzed. A two-tailed P<0.05 was considered statistically significant. Results:No significant differences were observed in age, sex, education level, or Mini-Mental State Examination (MMSE) scores ( t=1.80, χ2=0.41, t=0.17, t=1.77, all P>0.05). Compared with controls, the PIOD group showed significantly lower Sniffin′ Sticks scores ( t=28.70, P<0.001), prolonged oERP latencies and reduced amplitudes (all P<0.001). VBM revealed significantly reduced gray matter volume in the right orbitofrontal cortex (OFC) in the PIOD group ( t=5.38, P<0.001). SBM demonstrated decreased cortical thickness in the right OFC ( t=5.27, P<0.001), with no significant differences in folding index. The gray matter volume in the right OFC was negatively correlated with disease duration ( r=-0.61, P<0.001), but no significant correlations were found with Sniffin′ Sticks scores or oERP parameters. Conclusion:Patients with PIOD show atrophy in the right OFC, which correlates with disease duration, suggesting that persistent olfactory dysfunction may be associated with neurodegenerative changes.

Objective:To explore the alterations in gray matter morphology and contributing factors in patients with post-infectious olfactory dysfunction (PIOD) using voxel-based morphometry (VBM) and surface-based morphometry (SBM), thereby providing scientific insights into the neuropathological mechanisms underlying PIOD.Methods:A total of 46 PIOD patients (PIOD group) and 46 normosmic volunteers (control group) were recruited from the Smell and Taste Disorders Clinic of Beijing Anzhen Hospital, Capital Medical University, between January 2020 and December 2024. All participants underwent olfactory psychophysical tests (Sniffin′ Sticks) and olfactory event-related potential (oERP) examination. High-resolution T1-weighted 3D MRI structural images were obtained for both groups. VBM was employed to analyze inter-group differences in gray matter volume, while SBM was used to assess cortical thickness and folding index. Correlations between gray matter volume in significant difference brain regions and disease duration, Sniffin′ Sticks scores, oERP parameters were analyzed. A two-tailed P<0.05 was considered statistically significant. Results:No significant differences were observed in age, sex, education level, or Mini-Mental State Examination (MMSE) scores ( t=1.80, χ2=0.41, t=0.17, t=1.77, all P>0.05). Compared with controls, the PIOD group showed significantly lower Sniffin′ Sticks scores ( t=28.70, P<0.001), prolonged oERP latencies and reduced amplitudes (all P<0.001). VBM revealed significantly reduced gray matter volume in the right orbitofrontal cortex (OFC) in the PIOD group ( t=5.38, P<0.001). SBM demonstrated decreased cortical thickness in the right OFC ( t=5.27, P<0.001), with no significant differences in folding index. The gray matter volume in the right OFC was negatively correlated with disease duration ( r=-0.61, P<0.001), but no significant correlations were found with Sniffin′ Sticks scores or oERP parameters. Conclusion:Patients with PIOD show atrophy in the right OFC, which correlates with disease duration, suggesting that persistent olfactory dysfunction may be associated with neurodegenerative changes.

Objective To evaluate and summarise the best evidence on non-pharmacological preventive measures for lower limb lymphedema in patients with gynecologic malignancy so as to provide an evidence-based guidance for prevention of lower limb lymphedema.Methods Systematic searches were conducted from inception to 31th January,2024 on databases of UpToDate,BMJ Best Practice,the National Institute for Health and Care Excellence(NICE),the Oncology Nursing Society(ONS),Guidelines International Network(GIN),China Guideline Clearinghouse,Medlive,National Comprehensive Cancer Network(NCCN),Registered Nurses Association of Ontario(RNAO),American Society of Clinical Oncology(ASCO),European Society for Medical Oncology(ESMO),Cancer Australia(CA),National Lymphedema Network(NLN),Scottish Intercollegiate Guidelines Network(SIGN),Lymphedema Support Network(LSN),International Society of Lymphology(ISL),International Society of Nurses in Cancer Care,Lymphedema Association of Ontario,Lymphoedema United,Cochrane Library,Web of Science,PubMed,Scopus,OVID,Embase,CINAHL,VIP,Wangfang Data,CNKI and SinoMed for the relevant evidence in non-pharmacological preventive measures for lower limb lymphedema in patients with gynecological malignancy.Two researchers evaluated the quality of clinical decisions,expert consensus,systematic reviews and randomised controlled trials,while four investigators assessed the quality of the guidelines.Another two researchers performed data extraction and evidence summary.Results A total of 17 articles were included,comprising two clinical decisions,two guidelines,two systematic reviews,seven expert consensuses,one evidence summary,three randomised controlled trials.A total of 32 pieces of evidence were summarised across eight dimensions:prevention timing,evaluation element,general self-care,skin care,manual lymphatic drainage,compression therapy,exercise and health education.Conclusion This study provides an evidence-based guidance for prevention of lower limb lymphedema in patients with gynecological malignancy.Healthcare professionals should apply the best evidences based on the conditions,preferences,resource allocation,and other factors of the patients,to reduce limb lymphedema and improve the quality of life of the patients.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Pancreatic duct stents are essential devices for managing chronic pancreatitis,ductal strictures,and postoperative fistula.Conventional plastic and metal stents effectively facilitate pancreatic drainage but often cause infection,restenosis,or migration upon long-term implantation.An ideal stent should provide excellent biocompatibility,efficient drainage,and controllable biodegradation.With advances in material science and medical-engineering integration,stent technology has evolved from inert implantation to intelligent degradation.Biodegradable polymers and metals,particularly magnesium alloys(Mg-Zn-Mn),offer tunable mechanical strength,corrosion resistance,and in vivo degradability.Mg-2Zn-1.0Mn alloy achieves balanced strength and corrosion control through compositional optimization and surface modification.Polymeric stents such as polylactic acid and polydioxanone demonstrate favorable drainage and avoid secondary removal.Composite biodegradable stents,exemplified by the multi-rate ARCHIMEDES model,have received international approval.Supported by 3D printing and smart functionalization-such as drug-eluting or shape-memory designs-next-generation pancreatic stents may achieve integrated functions of support,repair,and tumor inhibition.Future research should emphasize interdisciplinary material design,degradation kinetics under physiological conditions,and long-term biocompatibility to accelerate clinical translation.