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: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Objective:To discuss the improvement effect of epicatechin(EC)on acetaminophen(APAP)-induced liver injury in the mice,and to clarify its possible mechanism.Methods:A total of 60 C57BL/6J mice were randomly divided into blank control group,APAP model group,low dose of EC group(10 mg·kg-1),middle dose of EC group(20 mg·kg-1)and high dose of EC group(40 mg·kg?1),with 12 mice in each group.Except for blank control group,the mice in the other groups were given intraperitoneal injection of APAP(200 mg·kg?1)to establish the liver injury models.At 1 h before APAP injection,the mice in low,middle and high doses of EC groups were intraperitoneally injected with 10,20 and 40 mg·kg-1 EC,respectively.A total of 36 nuclear factor E2-related factor 2(Nrf2)deficient mice(Nrf2-/-mice)were randomly divided into control group,APAP group and APAP+EC group,with 12 mice in each group.After modeling 24 h,the mice were sacrificed,and the blood and liver tissue of the mice were collected for subsequent detection.HE staining was used to observe the pathomorphology of the liver tissue in the mice in various groups;kit assay was used to detect the activities of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in serum of the mice in various groups and the myeloperoxidase(MPO)activity and the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),malondialdehyde(MDA),adenosine triphosphate(ATP),glutathione(GSH)and ferrous ion(Fe2?)in liver tissue of the mice in various groups;Western blotting method was used to detect the expression levels of nuclear factor-κB(NF-κB)and Nrf2 signaling pathway-related proteins in liver tissue of the mice in various groups.Results:The HE staining results showed that compared with APAP model group,the APAP-induced liver pathology injury in the mice in different doses of EC groups was significantly improved.Compared with blank control group,the levels of ALT and AST in serum of the mice in APAP model group were significantly increased(P<0.01).Compared with APAP model group,the activities of ALT and AST in serum of the mice in low,middle and high doses of EC groups were significantly decreased(P<0.05 or P<0.01).Compared with blank control group,the MPO activity and the levels of TNF-α and IL-1β in liver tissue of the mice in APAP model group were significantly increased(P<0.01).Compared with APAP model group,the MPO activity and the levels of TNF-α and IL-1β in liver tissue of the mice in low,middle and high doses of EC groups were decreased(P<0.05 or P<0.01).Compared with blank control group,the levels of MDA and Fe2? in liver tissue of the mice in APAP model group were significantly increased(P<0.05),and the levels of ATP and GSH were significantly decreased(P<0.05).Compared with APAP model group,the levels of MDA and Fe2? in liver tissue of the mice in low,middle and high doses of EC groups were significantly increased(P<0.05 or P<0.01),and the levels of ATP and GSH were significantly increased(P<0.01).Compared with blank control group,the expression levels of amino acid exchange transporter(xCT)and glutathione peroxidase 4(GPX4)proteins in liver tissue of the mice in APAP model group were significantly decreased(P<0.05);compared with APAP model group,the expression levels of xCT and GPX4 proteins in liver tissue of the mice in low,middle and high doses of EC groups were significantly increased(P<0.01).Compared with blank control group,the expression levels of nuclear factor-κB(NF-κB)p-p65 and phosphorylated NF-κB inhibitor α(p-IκBα)proteins in liver tissue of the mice in APAP model group were significantly increased(P<0.05);compared with APAP model group,the expression levels of NF-κB p-p65 and p-IκBα proteins in liver tissue of the mice in low,middle and high doses of EC groups were significantly decreased(P<0.01).Compared with blank control group,the expression levels of Nrf2 and heme oxygenase-1(HO-1)proteins in liver tissue of the mice in APAP model group were significantly increased(P<0.05);compared with APAP model group,the expression levels of Nrf2 and HO-1 proteins in liver tissue of the mice in low,middle and high doses of EC groups were significantly increased(P<0.01).Compared with control group,the ALT level in serum and the levels of MDA and Fe2+in liver tissue of the Nrf2-/-mice in APAP group were significantly increased(P<0.01),and the levels of ATP and GSH in liver tissue were significantly decreased(P<0.01).Conclusion:EC can improve APAP-induced liver injury in the mice,and its mechanism may be related to the inhibition of ferroptosis by activating the Nrf2/GPX4 signaling pathway.

Objective:To investigate the effects of psychosocial factors on early puberty and its sex specific differences.Methods:Bengbu Yuhui Longitudinal Study of Children Development Cohort, consisting of 1 162 students in grades 1-3 (524 girls) and their parents, was established in April 2021 in Bengbu, Anhui Province. The parents were surveyed by questionnaire to collect the information about their children's 56 items of psychosocial factor exposures, including 5 dimensions: major life events, early life adversity, interpersonal/relational conflict, family economic status and daily life troubles. Pubertal growth and physical examinations were conducted by trained professionals at baseline, the 1 st (May 2022), 2 nd (October 2022), 3 rd (May 2023), and 4 th (October 2023) follow-up surveys. In this study, the pubertal development status data were from the 4 th follow-up examination. Fianally, the valid data on pubertal development of 1 105 children were obtained, including the data from 510 girls (46.15%). Multinomial logistic regression model was used to analyze the association between psychosocial factors and early puberty, and the final predictors of early puberty were explored by using four models [least absolute shrinkage and selection operator (LASSO), multiple logistic regression, ridge regression, and Bayesian]. Results:The detection rates of early puberty in boys and girls were 13.60% and 16.30%, respectively. The median of intra-group absolute correlation of psychosocial factor exposure (0.042-0.066) was generally higher than that of inter-group among girls (0.031-0.059), while no similar diference was found among boys. LASSO model showed that moving house, being raised by someone other than parents, sexual abuse, peer conflict, high monthly household income, and high exposure to electronics on school days were predictors of early puberty in girls, while moving house and high monthly household income were the predictors of early puberty in girls in all four models (LASSO, multiple logistic regression, ridge regression, and Bayesian). Among boys, only a transient loss from family was a predictor of early puberty.Conclusion:Early puberty in children can be predicted by psychosocial factors, and there are gender-specific differences.

Objective:To evaluate the efficacy of dexmedetomidine-scalp nerve block (SNB) combined with general anesthesia in the patients with acute traumatic brain injury (TBI) undergoing craniotomy.Methods:In this randomized controlled trial, 74 American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex with acute TBI, aged 30-78 yr, with body mass index of 18-30 kg/m 2, underwent craniotomy for hematoma evacuation combined with decompressive craniectomy at the Traditional Chinese Medicine Hospital of Kunshan from January to December 2024, of the Glasgow Coma Scale score 8-12, were selected and divided into 2 groups ( n=37 each) using a random number table method: dexmedetomidine combined with ultrasound-guided SNB group (DS group) and ultrasound-guided SNB group (S group). Before anesthesia, dexmedetomidine was infused as a loading dose of 1 μg/kg over 10 min followed by an infusion of 0.3 μg·kg -1·h -1 until the end of operation. Ultrasound-guided SNB was performed after completion of intubation in both groups. The consumption of intraoperative fentanyl, propofol and remifentanil and the usage of vasoactive drugs were recorded. Before surgery (T 0), at 1 h after the start of surgery (T 1) and at the end of surgery (T 2), blood samples from the jugular bulbar and radial artery were collected, the jugular venous oxygen saturation was recorded, the arteriovenous oxygen content and cerebral oxygen uptake rate were calculated, and the occurrence of postoperative complications was also recorded. Results:Compared with group S, the consumption of fentanyl, propofol and remifentanil was significantly reduced, the usage rate of vasoactive drugs was decreased, the arteriovenous oxygen content and cerebral oxygen uptake rate were decreased at T 1 and T 2, the jugular venous oxygen saturation was increased, and the incidence of postoperative agitation was decreased in group DS ( P<0.05). Conclusions:Dexmedetomidine-SNB combined with general anesthesia can optimize the analgesic effect, improve cerebral oxygen supply and demand, reduce the occurrence of postoperative agitation when used in patients with acute TBI undergoing craniotomy.

Objective To investigate the impact of risk prevention and control on the quality efficiency of medical equipment procurement.Methods The medical equipment procurement projects with enhanced risk prevention measures during 2023(119 items)were assigned to an observation group,while those without strengthened risk control during 2022(118 items)were enrolled into a control group.The two groups were compared in terms of bid failure/rejection rates,procurement completion cycles(including procurement execution cycle and total procurement cycle)and procurement satisfaction.Statistical analysis was performed using SPSS 20.0 software.Results The observation group demonstrated significantly lower bid failure/rejection rates when compared with the control group(≥2 occurrences:5.88％vs.15.25％,P＜0.05).The procurement execution cycle was notably shorter in the observation group((69.16±78.65)d vs.(97.67±49.84)d,P＜0.05),though no significant difference was observed in total procurement cycle(P＞0.05).The observation group behaved better significantly than the control group in procurement efficiency,equipment performance,procedural compliance and post-purchase service satisfaction(all P＜0.05).Conclusion Risk prevention and control measures in medical equipment procurement effectively reduce bid failure/rejection risks while enhancing procurement quality efficiency.[Chinese Medical Equipment Journal,2025,46(3):81-85]

AIM To explore the clinical effects of Huayu Ditan Linao Decoction combined with Suhexiang Pills on elderly patients with cerebral hemorrhage in convalescent stage.METHODS One hundred and ten patients were randomly assigned into control group(55 cases)for 1-month intervention of both conventional treatment and rehabilitation training,and observation group(55 cases)for 1-month intervention of Huayu Ditan Linao Decoction,Suhexiang Pills,conventional treatment and rehabilitation training.The changes in clinical effects,TCM syndrome score,NIHSS score,FMA score,BI index,cerebrovascular function indices(dynamic resistance,average flow velocity,peripheral resistance,average flow rate),serum inflammatory indices(IL-6,hs-CPR,TNF-α)and serum oxidative stress indices(SOD,MDA)were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome score,NIHSS score,dynamic resistance,peripheral resistance,serum inflammatory indices,MDA(P＜0.05),and increased FMA score,BI index,average flow velocity,average flow rate,SOD(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the elderly patients with cerebral hemorrhage in convalescent stage,Huayu Ditan Linao Decoction combined with Suhexiang Pills can enhance clinical effects,improve limb functions and nerve functions,regulate serum inflammatory and oxidative stress indice,and promote prognosis.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

Objective To analyze the imaging features of cerebral small vessel disease in patients with type 2 diabetes mellitus by multimodal MRI.Methods The clinical data of 160 patients with cerebral small vessel disease admitted to our hospital from January to December 2020 were retrospectively analyzed.According to whether they were complicated with type 2 diabetes mellitus,they were divided into the diabetic group and the non-diabetic group,with 80 cases in each group.Both groups underwent multimodal MRI scans.And the severity of lacunar infarction,the severity of subcortical and periventricular white matter lesions,white matter integral and cerebral microbleeds of patients in the two groups were compared.Results The severity of lacunar infarction(χ2=34.076,P=0.001),subcortical white matter lesions(χ2=25.000,P=0.001),periventricular white matter lesions(χ2=22.895,P=0.001)and white matter integral(t=12.370,P=0.001)of patients in the diabetic group were significantly higher than those in the non-diabetic group.No cerebral microbleeds were detected in either group of patients.Conclusion Patients with cerebral small vessel disease and type 2 diabetes mellitus show characteristic multimodal MRI changes.The increase in the number of lacunar infarction lesions and the aggravation of white matter lesions can be used as the characteristic imaging basis for the diagnosis of type 2 diabetes mellitus related cerebral small vessel disease.