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 study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

Objective To observe the clinical efficacy and safety of ticagrelor tablets combined with atorvastatin calcium tablets in the treatment of cerebral thrombosis.Methods The patients with cerebral thrombosis were divided into control group and treatment group according to cohort methods.Two groups were given basic therapy.On the basic therapy,control group was given atorvastatin calcium 20 mg per time,once a day,orally;on the basic of control group,the treatment group received ticagrelor 90 mg per time,twice a day,orally.Two groups were treated for 4 months.The clinical efficacy,nerve function,blood viscosity,platelet parameters,brain injury markers and adverse drug reactions were compared between two groups.Results Treatment and control groups enrolled 119 and 117 cases,respectively.After treatment,the total effective rates of treatment and control groups were 91.60％(109 cases/119 cases)and 82.05％(96 cases/117 cases)with significant difference(P＜0.05).After treatment,the scale scores of treatment and control groups were(5.47±0.82)and(6.51±0.96)points;the plasma viscosity levels were(1.35±0.21)and(1.62±0.24)mPa·s,whole blood high shear viscosity levels were(3.67±0.51)and(4.01±0.59)mPa·s;the whole blood low shear viscosity levels were(6.12±0.93)and(7.05±1.07)mPa·s;the platelet adhesion rates were(30.52±3.81)％and(36.21±4.02)％;the mean platelet volumes were(12.75±1.86)and(15.42±2.06)fL;the carboxy-terminal hydrolase of ubiquitin levels were(0.39±0.06)and(0.51±0.07)μg·L-1;the key protein antigen-5 of aging levels were(90.76±12.23)and(81.64±11.95)μg·L-1;and the differences were statistically significant between two groups(all P＜0.05).The adverse drug reactions of two groups were nausea,vomiting,bleeding,abdominal pain and diarrhea.The total incidences of adverse drug reactions in treatment and control groups were 5.04％and 4.27％,without significant difference(P＞0.05).Conclusion Ticagrelor tablets combined with atorvastat in calcium tablets have a significant clinical efficacy in the treatment of patients with cerebral thrombus,which can significantly improve the neurological function,blood viscosity,brain injury markers,and platelet parameters of patients,without increasing the incidence of adverse drug reactions.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

The presence of food-borne pathogenic bacteria poses a severe threat to human health. Therefore,it is essential to develop effective methods for bacteria detection. Herein,a method based on digital polymerase chain reaction (PCR) chip was developed for rapid and effective detection of three kinds of common food-borne bacteria (Staphylococcus aureus,Salmonella typhimurium and Listeria monocytogenes). Driven by centrifugal force,samples could be easily loaded and digitized in 15 min. PCR results showed that the positive microchambers in the chip could be identified after 25 thermal cycles. The chip had advantages in the quantitative detection of bacterial nucleic acid at low concentration,which could effectively avoid false negative results. Multiple detection of bacterial samples with concentration of 105-108 CFU/mL could also be realized using this chip. Compared with fluorescent quantitative PCR,this method had higher accuracy and sensitivity,especially for detection of targets at low concentration.

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 efficiency and safety of combining lenvatinib with DEB-TACE for the treatment of unresectable large hepatocellular carcinoma,accompanied by PVTT,in order to provide insights into its potential as a therapeutic approach.Method:Patients with hepa-tocellular carcinoma and portal vein tumor thrombus,who were diagnosed and treated at Linyi Can-cer Hospital between June 2019 and June 2021,were chosen as the subjects of this study.Patient allocation into the experimental group(23 cases)and control group(27 cases)was based on indi-vidual preferences,ensuring a random distribution of participants.The DEB-TACE treatment was administered to the control group,while the experimental group received a combination of DEB-TACE and lenvatinib.The effectiveness of lenvatinib was assessed in the immediate post-surgery period,the patients'survival was monitored,and any associated side effects were documented.Result:3 months after treatment,the objective remission rates of the experimental group and the control group were 91.31％and 66.67％,and the disease control rates were 100％and 77.78％.The difference was statistically significant(P＜0.05).3 months after treatment,the regression rates of tumor thrombus in the experimental group and the control group were 60.87％and 29.63％,the difference was statistically significant(P＜0.05).The progression free survival time of the experi-mental group and the control group was 11 months and 8 months,the difference was statistically significant(P＜0.05);The median survival time of the experimental group and the control group was 20 months and 14 months,and the difference was statistically significant(P＜0.05).The main ad-verse reactions of the experimental group were hypertension,diarrhea,hand foot syndrome,rash,fatigue,loss of appetite,etc.,all of which were less than or equal to grade 3,and could be basically relieved after symptomatic treatment.Conclusion:The combination of DEB-TACE and lenvatinib is proven to be a safe and well-tolerated treatment for unresectable large hepatocellular carcinoma with portal vein tumor thrombus.This therapy not only effectively controls tumor progression but also prolongs survival time.

ObjectiveTo observe the efficacy and safety of Tongguan Capsule（通冠胶囊）on ventricular remodeling in patients after acute myocardial infarction （AMI）， and to explore the possible mechanism. MethodsA total of 53 ST-segment elevation myocardial infarction （STEMI） patients were collected and randomly divided into 26 cases in the treatment group and 27 cases in the control group. The control group was given conventional therapy after percutaneous coronary intervention （PCI） for AMI， and the treatment group was given Tongguan Capsules （4.5 g each time， 3 times a day） on the basis of the control group. The course of treatment was 12 weeks. Echocardiographic data and stool samples were collected from subjects before and after the intervention， and left ventricular ejection fraction （LVEF）， left ventricular end-diastolic volume index （LVEDVi）， left ventricular end-systolic volume index （LVESVi）， left ventricular mass index （LVMi） were measured and calculated， so as to compare the number of cases of left ventricular remodeling in the two groups. At the same time， 16S rDNA sequencing was performed on the stool samples to analyze the diversity of gut microbiota （GM）， the composition of the GM， the GM difference between the groups； recording the incidence of major adverse cardiovascular events （MACEs） and adverse reactions of patients in the two groups during the study period； and performing Spearman's correlation analyses of the post-treatment flora data with LVEF， LVEDVi， LVESVi， LVM， and LVMi in the two groups. ResultsOne case fail to follow up in the treatment group and 2 cases fail to follow up in the control group， and 25 cases in each of the two groups were finally included in the analysis. LVEDVi， LVESVi， and LVMi of the control group after treatment were higher than those before treatment （P＜0.05）； after treatment， LVEDVi， LVESVi and LVMi in the treatment group were lower than those in the control group （P＜0.05）. Left ventricular remodeling occurred in 5 cases （20.00%） in the treatment group and 13 cases （52.00%） in the control group， and the incidence of left ventricular remodeling in the treatment group was lower than that in the control group （P=0.03）. After treatment， the ACE estimation and Chao estimation of bacterial abundance in the treatment group were higher than that before treatment and that in the control group （P＜0.05）. The treatment group showed an increase in Mycobacterium anisopliae phylum and a decrease in Mycobacterium thickum， Mycobacterium anisopliae phylum， and Mycobacterium patella phylum after treatment （P＜0.05）. When comparing between groups after treatment， the relative abundance of Prevotella， Agathobacter， Dialister， Eubacterium coprostanoligenes group was up-reuglated and the relative abundance of Enterococcus was down-regulated in the treatment group（P＜0.05 or P＜0.01）. There was no statistically significant difference in the incidence of MACEs and the occurrence of adverse reactions between groups during treatment （P＞0.05）. The results of correlation analysis showed that Prevotella were positively correlated with LVEF and negatively correlated with LVEDVi， LVESVi， LVM， and LVMi （P＜0.01）. Agathobacter group were negatively correlated with LVEDVi， LVESVi （P＜0.01）； Enterococcus group were positively correlated with LVESVi （P＜0.05）. ConclusionTongguan Capsules can improve ventricular remodeling in patients with acute ST-segment elevation myocardial infarction with better safety； its mechanism may be related to adjusting the enrichment of related bacteria such as Prevotella， Dialister and Enterococcus and other related bacterial genera， increasing the colonization and diversity of beneficial bacteria， and adjusting the structure of GM.

Since Curcumae Radix decoction pieces have multiple sources, it is difficult to distinguish depending on traditional cha-racters, and the mixed use of multi-source Curcumae Radix will affect its clinical efficacy. Heracles Neo ultra-fast gas phase electronic nose was used in this study to quickly identify and analyze the odor components of 40 batches of Curcumae Radix samples from Sichuan, Zhejiang, and Guangxi. Based on the odor fingerprints established for Curcumae Radix decoction pieces of multiple sources, the odor components was identified and analyzed, and the chromatographic peaks were processed and analyzed to establish a rapid identification method. Principal component analysis(PCA), discriminant factor analysis(DFA), and soft independent modeling cluster analysis(SIMCA) were constructed for verification. At the same time, one-way analysis of variance(ANOVA) combined with variable importance in projection(VIP) was employed to screen out the odor components with P<0.05 and VIP>1, and 13 odor components such as β-caryophyllene and limonene were hypothesized as the odor differential markers of Curcumae Radix decoction pieces of diffe-rent sources. The results showed that Heracles Neo ultra-fast gas phase electronic nose can well analyze the odor characteristics and rapidly and accurately discriminate Curcumae Radix decoction pieces of different sources. It can be applied to the quality control(e.g., online detection) in the production of Curcumae Radix decoction pieces. This study provides a new method and idea for the rapid identification and quality control of Curcumae Radix decoction pieces.
Drugs, Chinese Herbal/analysis* ; Electronic Nose ; China ; Plant Roots/chemistry* ; Limonene/analysis* ; Chromatography, High Pressure Liquid