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.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To summarize the clinical characteristics,therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma(HL).Methods:A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled,and their clinical data,including sex,age,pathological type,Ann Arbor stage,ECOG score,blood test,β2-microglobulin,lactate dehydrogenase level,albumin level were collected.The clinical characteristics,therapeutic effect and long-term prognosis of the patients were summarized and analyzed.Results:In classical HL,nodular sclerosis HL accounted for the highest proportion of 51.6％,followed by mixed cellularity HL(36.5％),lymphocyte-rich classical HL(3.2％),and lymphocyte depletion HL(0.7％),while nodular lymphocyte predominant HL accounted for 4.8％.The 3-year overall survival(OS)rate of HL patients was 89.8％,and 5-year OS was 85.0％.The 3-year progression-free survival(PFS)rate was 73.4％,and 5-year PFS was 63.1％.Multivariate regression analysis indicated that IPI score was an independent negative factor,while hemoglobin(Hb)level was an independent positive factor for OS in HL patients.When the mediastinal mass size was 9.2 cm,it was most significant to judge the survival status of HL patients.5-year OS and 5-year PFS were 97.4％and 76.0％in early-stage HL patients without large mass,respectively,while in patients with advanced-stage HL was 83.4％and 55.9％(both P＜0.05).After 2-4 courses of treatment,the overall response rate(ORR)of patients who received chemotherapy combined with radiotherapy was 95.0％,while that was 89.6％in those with chemotherapy alone.Conclusions:The overall prognosis of patients with HL is satisfactory,especially those in early-stage without large mass.IPI score and Hb level are independent risk factors for the prognosis of HL patients.A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.
Humans ; COVID-19 ; SARS-CoV-2 ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Graft vs Host Disease

Objective: To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction (HFpEF) and the correlation with myocardial amyloid deposition. Methods: This was a retrospective case-control study. Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected. Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group. The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside (8-oxo-G) and 8-oxidized guanine deoxyriboside (8-oxo-dG) to evaluate the oxidation of RNA and DNA in cardiomyocytes. Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value, patients were divided into high-absorbance group and low-absorbance group. Congo red staining was used to compare myocardial amyloid deposition between the two groups. Results: The mean age of patients in HFpEF group was (91.8±3.7) years, 24 (92.3%) were males. The mean age of patients in control group was (91.7±3.7) years old, 11 (84.6%) were males. The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group (0.313 8 (0.302 2, 0.340 6) vs. 0.289 2 (0.276 7, 0.299 4), Z=-3.245, P=0.001). The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups (0.300 0 (0.290 0, 0.322 5) vs. 0.300 0 (0.290 0, 0.320 0), Z=-0.454, P=0.661). Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group ((85.0%, 17/20) vs. (31.6%, 6/19), P=0.001). Conclusion: The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure. Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.
Aged ; Male ; Humans ; Aged, 80 and over ; Female ; Heart Failure/pathology* ; Retrospective Studies ; Stroke Volume ; Case-Control Studies ; Nucleic Acids ; 8-Hydroxy-2'-Deoxyguanosine ; Myocytes, Cardiac/pathology* ; RNA ; Oxidative Stress ; Guanine ; Ventricular Function, Left

AIM: To observe changes in fundus microcirculation of myopic adolescents after wearing orthokeratology by applying optical coherence tomography angiography(OCTA).METHODS: Prospective study. A total of 40 cases(40 eyes)of adolescents with low to moderate myopia who chose orthokeratology to correct visual acuity at our hospital from April 2021 to June 2022 were collected. The uncorrected distant visual acuity and axial length were evaluated at 1, 3 and 6mo before and after wearing orthokeratology, respectively. Furthermore, the changes in superficial vessel density(SVD), deep vessel density(DVD), central retinal thickness(CRT), foveal avascular zone area(FAZ-A), foveal avascular zone perimeter(FAZ-P), retinal nerve fiber layer(RNFL)thickness and radial peripapillary capillaries density(RPCD)were observed by applying OCTA.RESULTS: The uncorrected distant visual acuity was significantly improved at 1, 3 and 6mo after wearing orthokeratology(P<0.001). There was no statistically significant difference in axial length before and after wearing orthokeratology(P>0.05). Moreover, there were significant differences in both SVD of fovea quadrant and DVD of fovea and lower quadrant(P<0.01), but there were no differences in CRT, FAZ-A and FAZ-P, RNFL thickness and RPCD(P>0.05).CONCLUSION: Wearing orthokeratology can significantly improve visual acuity and increase local retinal vessel density in the macula in adolescents with low to moderate myopia.

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.

Humans ; Adult ; Mucormycosis ; Leukemia, Myeloid, Acute/complications* ; Acute Disease ; Antifungal Agents

Child ; Humans ; Factor VII Deficiency