Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.

OBJECTIVE To summarize the current situation of pharmaceutical clinic service in our hospital over the past five years， and explore sustainable development strategies for service models of pharmaceutical clinics. METHODS A retrospective analysis was conducted on the consultation records of patients who registered and established files at the pharmaceutical clinic in our hospital from January 2019 to December 2023. Statistical analysis was performed on patients’ general information， medication- related problems， and types of pharmaceutical services provided by pharmacists. RESULTS A total of 963 consultation records were included， among which females aged 20-39 years accounted for the highest proportion （66.04%）； obstetrics and gynecology- related consultations accounted for the largest number of cases. Additionally， 80 patients attended follow-up visits at our hospital’s pharmaceutical clinic. A total of 1 029 medication-related issues were resolved， including 538 cases of drug consultations （52.28%）， 453 medication recommendations （44.02%）， 22 medication restructuring（2.14%）， and 16 medication education （1.55%）； the most common types of medication-related problems identified were adverse drug events（70.07%）. CONCLUSIONS Although the pharmaceutical clinic has achieved recognition from clinicians and patients， challenges such as low awareness among healthcare providers and the public persist. Future efforts should focus on strengthening information technology construction， enhancing pharmacist training， and establishing various forms of outpatient pharmaceutical service models.

ObjectiveTo compare colonoscopy compliance rates under different screening strategies, to explore ways to enhance colonoscopy compliance among residents with colorectal carcinoma. MethodsResidents aged between 50‒80 years were recruited through extensive community outreach and voluntary participation. A total of 210 630 residents who participated in the colorectal carcinoma screening program in Jiading District, Shanghai, between 2013 and 2019 were selected as the research subjects. All subjects underwent a colorectal carcinoma risk assessment questionnaire survey and two fecal occult blood tests (FOBT). Positive results in the initial screening were defined as a positive questionnaire survey or a positive result in at least one FOBT. Participants with positive initial screening results were advised to undergo colonoscopy screening in a hospital. Colonoscopy results were collected from hospital reports and physician follow-ups. Compliance with colonoscopy was analyzed under different screening strategies to identify possible factors influencing residents’ willingness to undergo the procedure. ResultsA total of 21 403 individuals (10.16%) were identified as positive with the questionnaire survey, 31 595 individuals (15.00%) tested positive with at least one FOBT. Combined questionnaire and FOBT positivity was observed in 3 501 individuals (1.66%). Among the 48 453 individuals with positive initial screening results, 17 230 (35.56%) underwent colonoscopy, and a total of 315 cases of colorectal cancer were detected. The sensitivity, specificity value of FOBT initial screening were 83.81% and 84.66%, respectively. According to the combined risk assessment and FOBT initial screening preliminary screening, the lowest colonoscopy compliance rate (25.63%) was observed among individuals with only a positive questionnaire, and the highest compliance rate (52.55%) was among those with both positive questionnaire survey and two positive FOBT results. Multivariate analysis revealed that FOBT positivity had the greatest impact on colonoscopy compliance. Those with one positive FOBT test result were 2.64 times more likely to undergo colonoscopy screening than those with negative FOBT results, while individuals with two positive FOBT results were 3.18 times more likely to do so. After adjusting for FOBT results, individuals with positive questionnaire survey results were 1.43 times more likely to undergo colonoscopy screening than those with negative results (95%CI: 1.34‒1.52). Compared to questionnaire-based risk assessment, FOBT results were more influential in determining compliance with colonoscopy. ConclusionThe choice of initial screening method significantly impacts residents’ compliance with colonoscopy. While implementing colorectal carcinoma screening programs, it is necessary to strictly adhere to screening protocols, including risk assessment and FOBT. Additionally, efforts should be made to raise public awareness, encouraging residents to actively participate in risk assessments and FOBT, thereby improving their compliance with colonoscopy.

Objective To investigate the relationship between cyclin A2 (CCNA2) and the prognosis of colon cancer, and its possible mechanism from the perspective of immune infiltration. Methods We downloaded the transcriptome data of colon cancer patients from The Cancer Genome Atlas database. Clinicopathological feature analysis and survival analysis were performed based on the expression levels of CCNA2. A total of 75 specimens of colon cancer and normal tissues were collected, and the expression level of CCNA2 was analyzed using immunohistochemical methods. Multivariate analysis was conducted to explore its relationship with clinicopathological features. Gene Set Enrichment Analysis (GSEA) was used to assess the potential molecular functions of CCNA2 in colon cancer. CIBERSORT algorithm was applied to calculate the correlation between CCNA2 and immune-cell infiltration in colon cancer. Results Database and immunohistochemical analyses indicated that CCNA2 was expressed at a significantly higher level in colon cancer tissues than normal tissues (P<0.001). The overall survival, disease-specific survival, and progression-free interval were all longer in the group with high CCNA2 expression than the group with low expression (all P<0.05). In tumor tissues, the expression level of CCNA2 decreased with increased pathological and TNM stages (P<0.05). The expression level of CCNA2 in normal tissues was consistently lower than that in colon cancer tissues across all clinical stages (all P<0.001). GSEA suggested that Wnt/β-catenin, KRAS, and other signaling pathways were enriched when CCNA2 was lowly expressed. CIBERSORT analysis revealed an increase in the infiltration of immune cells such as regulatory T cells and macrophages M0 when CCNA2 expression was low. Conclusion CCNA2 is highly expressed in colon cancer and closely associated with grade of pathology and TNM stage. It may recruit regulatory T cells through the KRAS and Wnt/β-catenin pathways, thereby reducing immune-cell infiltration and promoting colon cancer progression, leading to poor prognosis.

Objective: To investigate the effects of Zuogui Jiangtang Yishen Formula (左归降糖益肾方, ZGJTYSF) in regulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) signaling axis on pyroptosis in rats with diabetic kidney disease (DKD). Methods: Fifty male specific pathogen-free (SPF) grade Goto-Kakizaki (GK) rats (12 weeks old) were fed a high-fat diet for one month to establish an early DKD model. Model establishment was confirmed when fasting blood glucose (FBG) ≥ 11.1 mmol/L and urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g. The successfully modeled early DKD rats were randomly divided by random number table into five groups (n = 10 per group): model group; dapagliflozin group (1.0 mg/kg, by gavage, served as positive control); and low-, medium-, and high-dose of ZGJTYSF groups (4.9, 9.9, and 19.9 g/kg, respectively, by gavage). Age-matched male SPF Wistar rats (n = 10) served as control group. Rats in control and model groups were gavaged with equivalent volumes of distilled water. Treatment lasted 12 weeks. Changes in uACR, FBG, and renal function were observed in all groups. Hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining were used to observe renal histopathological changes. Immunohistochemistry was performed to detect the localization and expression of caspase-1, GSDMD, and NLRP3 in rat renal tissues. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was utilized to detect pyroptosis in renal tissues. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were applied to detect mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, interleukin (IL)-1β, and IL-18. Results: Compared with model group, all doses of ZGJTYSF showed reductions in FBG, with medium- and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12 (P < 0.05). For uACR, all doses of ZGJTYSF groups exhibited a decreasing trend, with high-dose of ZGJTYSF group being significantly lower than low- and medium-dose of ZGJTYSF groups at week 12 (P < 0.05) and showing no significant difference from dapagliflozin group (P > 0.05). No significant differences in renal function parameters (serum creatinine, blood urea nitrogen, and uric acid) were observed among groups (P > 0.05). Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group, with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group. Immunohistochemistry demonstrated significantly reduced expression of caspase-1, GSDMD, and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group (P < 0.05 or P < 0.01), while the differences in low- and medium-dose of ZGJTYSF groups were not statistically significant (P > 0.05). TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups (P < 0.01), indicating a marked reduction in pyroptotic cells. Molecular analysis revealed that compared with model group, both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 in renal tissues (P < 0.01), while low- and medium-dose of ZGJTYSF groups showed downward trends without statistical significance (P > 0.05). Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis, thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Cancer represents a major worldwide disease burden marked by escalating incidence and mortality. While therapeutic advances persist, developing safer and precisely targeted modalities remains imperative. Nanomedicines emerges as a transformative paradigm leveraging distinctive physicochemical properties to achieve tumor-specific drug delivery, controlled release, and tumor microenvironment modulation. By synergizing passive enhanced permeation and retention effect-driven accumulation and active ligand-mediated targeting, nanoplatforms enhance pharmacokinetics, promote tumor microenvironment enrichment, and improve cellular internalization while mitigating systemic toxicity. Despite revolutionizing cancer therapy through enhanced treatment efficacy and reduced adverse effects, translational challenges persist in manufacturing scalability, longterm biosafety, and cost-efficiency. This review systematically analyzes cutting-edge nanoplatforms, including polymeric, lipidic, biomimetic, albumin-based, peptide engineered, DNA origami, and inorganic nanocarriers, while evaluating their strategic advantages and technical limitations across three therapeutic domains: immunotherapy, chemotherapy, and radiotherapy. By assessing structure-function correlations and clinical translation barriers, this work establishes mechanistic and translational references to advance oncological nanomedicine development.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Nanoparticles/chemistry* ; Animals ; Nanomedicine/methods* ; Drug Delivery Systems/methods* ; Drug Carriers/chemistry* ; Radiotherapy/methods*

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation