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 evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Objective To explore the therapeutic effect and mechanism of pressing and rubbing method on myofascial pain syndrome(MPS)rats.Methods A total of 12 rats were randomly selected from 60 rats as the normal group,and the remaining rats were used to construct the MPS model by blunt strike combined with centrifugal exercise.Then 48 successfully modeled rats were randomly divided into model group,pressing and rubbing method group,pressing and rubbing method + Dantrolene[ryanodine receptor(RyR)inhibitor]group,pressing and rubbing method + normal saline group,with 12 rats in each group.The mechanical pain threshold was measured by von-Frey method.Detection of soft tissue tension,electromyography was performed;the ultrastructure of the pain point tissue was observed by transmission electron microscopy.The content of calcium ion(Ca2+)in the tissue of trigger point was detected by colorimetry.The protein expressions of dihydropyridine receptor(DHPR)α1,RyR and acetylcholinesterase(AChE)in the pain points of rats were detected by Western Blot.Results Compared with the normal group,the mechanical pain threshold,soft tissue tension in trigger point and the protein expressions of DHPRα1,RyR and AChE in the model group were decreased and the Ca2+ + content was increased(all P＜0.05),and the peak potential with higher amplitude was observed in the electromyogram.The ultrastructure of the trigger point tissue was damaged.Compared with the model group,the mechanical pain threshold,soft tissue tension of trigger point and the protein expressions of DHPRα1,RyR and AChE in the trigger point tissue of the rats in the pressing and rubbing method group and the pressing and rubbing method + normal saline group were increased,and the Ca2+ content was decreased(all P＜0.05),the electromyography was restored to be stable,the ultrastructural damage of the trigger point tissue was alleviated.Compared with the pressing and rubbing method group,the mechanical pain threshold,soft tissue tension of trigger point and protein the expressions of DHPRα1,RyR and AChE in the trigger point tissue of the rats in the pressing and rubbing method + Dantrolene group were decreased,and the Ca2+ content was increased(all P＜0.05),the electromyogram showed electrical activity changes,the ultrastructure of the trigger point tissue was damaged.Conclusion The pressing and rubbing method may improve MPS in rats by activating the DHPR/RyR signaling pathway.

Objective To analyze the correlation between the comorbidity of chronic diseases and concurrent traditional Chinese medicine(TCM)constitutions in the elderly in Guangzhou.Methods From the physical examination data of 3 communities in Guangzhou,3 078 elderly people were selected as the survey objects,and association analysis was performed for mining the association rules between the chronic disease comorbidity and concurrent TCM constitution types of the elderly with different demographic characteristics.Results The comorbidity rate of chronic diseases in the elderly of Guangzhou area was 76.54％(2 356/3 078).In the elderly population of Guangzhou area,the correlation of chronic disease comorbidity with the concurrent constitution of tendentious blood stasis constitution and phlegm-damp constitution had the highest confidence,which was 95.87％.The correlation of chronic disease comorbidity with the gender showed that the concurrent constitution was similar in the elderly with different genders.The correlation of chronic disease comorbidity with the concurrent constitution of phlegm-damp constitution and tendentious yin deficiency constitution in the male elderly had the confidence of 94.38％,and the correlation of chronic disease comorbidity with the concurrent constitution of phlegm-damp constitution and tendentious blood stasis constitution in the female elderly had the confidence of 97.46％.With the increase of the age,the biased constitution of the elderly with chronic diseases gradually developed into the concurrent constitution of phlegm blended with blood stasis,and the concurrent constitution of qi deficiency constitution and yang deficiency constitution became the predominated.Conclusion The comorbidity rate of chronic diseases in the elderly is high.The association patterns of the comorbidity of chronic diseases with concurrent constitution types vary in different age groups.Medical institutions can condition the concurrent constitution with Chinese medicine therapy according to the characteristics of the concurrent constitutions of the elderly,and then can improve the comorbidity of chronic diseases in the elderly.

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 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

Aim To investigate the protective effect of orcinol glucoside on dexamethasone(DEX)-induced osteoblast injury and its mechanism. Methods Primary osteoblasts were extracted from calvaria of neonatal mice and cultured in medium with DEX(1 μmol•L

Humans ; Temperature ; Cities/epidemiology* ; Hot Temperature ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Mortality

OBJECTIVES: To explore the difference in CT values between pulmonary thromboembolism and postmortem clot in postmortem CT pulmonary angiography (CTPA) to further improve the application value of virtual autopsy. METHODS: Postmortem CTPA data with the definite cause of death from 2016 to 2019 were collected and divided into pulmonary thromboembolism group (n=4), postmortem clot group (n=5), and control group (n=5). CT values of pulmonary trunk and left and right pulmonary artery contents in each group were measured and analyzed statistically. RESULTS: The average CT value in the pulmonary thromboembolism group and postmortem clot group were (168.4±53.8) Hu and (282.7±78.0) Hu, respectively, which were lower than those of the control group (1 193.0±82.9) Hu (P<0.05). The average CT value of the postmortem clot group was higher than that of the pulmonary thromboembolism group (P<0.05). CONCLUSIONS CT value is reliable and feasible as a relatively objective quantitative index to distinguish pulmonary thromboembolism and postmortem clot in postmortem CTPA. At the same time, it can provide a scientific basis to a certain extent for ruling out pulmonary thromboembolism deaths.
Humans ; Autopsy ; Thrombosis ; Pulmonary Embolism/diagnostic imaging* ; Tomography, X-Ray Computed ; Angiography ; Cadaver