1.Application of CRISPR/Cas System in Precision Medicine for Triple-negative Breast Cancer
Hui-Ling LIN ; Yu-Xin OUYANG ; Wan-Ying TANG ; Mi HU ; Mao PENG ; Ping-Ping HE ; Xin-Ping OUYANG
Progress in Biochemistry and Biophysics 2025;52(2):279-289
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.
2.Exploration of Party-building leadership in promoting hospital culture construction in the new era: taking Xi’an No. 9 Hospital as an example
Louyan MA ; Yi WANG ; Zhen ZHEN ; Mi PANG ; Ting HE ; Puyan WEN ; Juxian ZHENG
Chinese Medical Ethics 2025;38(3):398-402
Hospital culture is the sum of common values, codes of conduct, and working methods formed by internal employees within the hospital, and it is the spiritual pillar and core of cohesion of the hospital. Party-building leadership plays an important role in promoting hospital culture construction, including strengthening values guidance, enhancing team cohesion, facilitating management system innovation, and shaping social image and brand value. By analyzing the effectiveness of a series of Party-building activities carried out by Xi’an No. 9 Hospital in recent years, this paper explored the effect and significance of Party-building leadership in promoting hospital culture construction in the new era, as well as proposed guiding strategies for strengthening Party-building work in promoting hospital culture construction in the new era, so as to promote high-quality development of the hospital.
3.The Effects of Tai Chi Training on Bone Density,Bone Turnover Markers,and Heart Rate Variability in High-Risk Osteoporosis Population
Jiaming LIN ; Chao LI ; Wei ZHAO ; Jun ZHOU ; Xiaoying CHEN ; Xiangyu XI ; Haijun HE ; Baohong MI ; Yuefeng CHEN ; Weiheng CHEN
Journal of Traditional Chinese Medicine 2025;66(15):1566-1571
ObjectiveTo explore the effects of the Tai Chi training on bone density, bone turnover markers, and heart rate variability for people with high-risk osteoporosis, and to provide evidence for the prevention of osteoporosis at early stage. MethodsSixty-six cases of people with high risk of osteoporosis were included, and they were divided into 33 cases each in the intervention group and the control group using the random number table method. The control group received osteoporosis health education three times a week, and the intervention group received Tai Chi training under the guidance of a trainer three times a week for 40 mins each time on the basis of the control group, and both groups were intervened for 12 weeks. Dual-energy X-ray absorptiometry was used to measure the bone density of L1~L4 vertebrae, bilateral femoral necks and bilateral total hips in the two groups before and after the intervention; enzyme-linked immunosorbent assay was used to determine bone turnover markers before and after the intervention, including pro-collagen type Ⅰ pro-amino-terminal prepropyl peptide (P1NP) and β-collagen type Ⅰ cross-linking carboxy-terminal peptide (β-CTX). Seven cases with good compliance in the intervention group were selected. After wearing the heart rate sensor, they successively performed Tai Chi training and walking activities recommended by the guideline for 20 mins each, and the heart rate variability (HRV) during exercise was collected, including time-domain indexes such as standard deviation of normal sinus intervals (SDNN), root-mean-square of the difference between adjacent RR intervals (RMSSD), frequency-domain metrics such as low-frequency power (LF), high-frequency power (HF), and low-frequency/high-frequency power ratio (LF/HF), as well as nonlinear metrics such as approximate entropy (ApEn), sample entropy (SampEn). ResultsFinally, 63 cases were included in the outcome analysis, including 30 cases in the intervention group and 33 cases in the control group. After the intervention, the differences of L1~L4 vertebrae, bone density of bilateral femoral neck and bilateral total hip in the intervention group were not statistically significant when compared with those before intervention (P>0.05), while the bone density of all parts of the control group decreased significantly compared with that before intervention (P<0.05), and the difference in the bone density of the L1~L4 vertebrae, bilateral femoral neck, and the right total hip before and after the intervention of the intervention group was smaller than that of the control group (P<0.05). The differences in P1NP and β-CTX between groups before and after intervention was not statistically significant (P>0.05). Compared with walking exercise, LF decreased, HF increased and LF/HF decreased during Tai Chi exercise (P<0.05); the time domain indexes and non-linear indexes between groups had no statistically significant difference (P>0.05). ConclusionTai Chi exercise can maintain lumbar, hip, and femoral bone density and improve sympathetic/parasympathetic balance in people at high risk for osteoporosis, but cannot significantly improve bone turnover markers.
4.Analysis of the effects of national centralized drug volume-based procurement policy in public medical institutions of the Guangxi Zhuang Autonomous Region
Zheng ZENG ; Liucen WU ; Zhenguang HUANG ; Wenli HE ; Zhengcheng MI ; Xiangwei XIE ; Siduo SU ; Guicheng LIANG ; Yaoling LIAO ; Hongliang ZHANG
China Pharmacy 2024;35(5):518-523
OBJECTIVE To investigate the implementation effects of the national centralized drug volume-based procurement policy (abbreviated as “national centralized procurement policy”) in Guangxi Zhuang Autonomous Region prefecture, and to provide a reference for the future centralized drug procurement work of the medical institution. METHODS Drug procurement data before and after policy implementation were included in the study. The six secondary indicators (such as availability, affordability, and drug safety) and eighteen third-level indicators (such as completion rate of agreed purchase volume, affordability level, drug revenue proportion) were introduced, guided by the policy objectives and issues of concern to policy beneficiaries. Descriptive statistics was adopted to analyze the data before and after policy implementation (in 2019 and 2020) in terms of differences and change trends. RESULTS In terms of accessibility, the participation rate of medical institutions in Guangxi Zhuang Autonomous Region was 92.55%, the proportion of diseases involved and median completed procurement rate were 40.16%, and 287.82% respectively, and the total centralized delivery rate was 97.20%. In terms of affordability, the total reduction amplitude in drug price was 74.80% from 2019 to 2022; the charge for medicine per capita in hospitalization, the proportion of medicine used for outpatient service and hospitalization, decreased by 17.61%, 10.22%, and 20.10% in order; the burden levels on medical fares for patients were all below 1 in addition to chronic diseases, and anti-tumor drugs. In terms of the impact on medicine, the ratio of adverse drug reaction event cases in 2022 was 66.00%, an increase of 1.29% compared to the previous; since the implementation of the policy, 12 drugs from local pharmaceutical enterprises from Guangxi Zhuang Autonomous Region had passed the consistency evaluation, and the market concentration rate of the top 8 pharmaceutical companies was less than 20.00%. In terms of the impact on healthcare and medical insurance, the public medical institutions achieved generic substitution for originator drugs mostly until 2022; about 9.12% of drugs that were non- centrally purchased in the same category were used; 63.39% of people under investigation did not show a need for a second dressing change; drug expenditure decreased by 2.459 billion yuan. CONCLUSIONS The national centralized procurement policy achieves a significant effect in Guangxi Zhuang Autonomous Region. On the other hand, attention should be paid to these suggestions as follows: expanding the category of drugs used in clinic, conducting clinically comprehensive evaluation of selected drugs, and improving reasonable allocation strategy, etc.
5.Analysis of blood testing indicators in HIV patients co-infected with different genotypes of HCV in Kunming area of Yunnan Province
LIU Junyi ; KANG Lijuan ; WANG Shimin ; ZHU Yantao ; ZHANG Mi ; ZHANG Nian ; XIE Qi ; LIU Shifang ; YANG Jiantao ; LI Xiao ; HE Quanying ; WANG Jiali
China Tropical Medicine 2024;24(3):252-
Objective To understand the genotyping of human immunodeficiency virus (HIV) co-infected hepatitis C virus (HCV) patients in Yunnan Province, and to analyze the differences in viral load, biochemical indicators, and blood routine indicators among different genotypes, in order to provide a laboratory basis for the diagnosis and clinical treatment of HIV/HCV co-infected patients. Methods From November 2022 to June 2023, the serum samples and basic information of patients diagnosed with HIV/HCV co-infection were collected in the antiviral outpatient clinic of Yunnan Provincial Hospital of Infectious Diseases. The HCV viral load was detected by one-step qRT-PCR amplification, the positive samples were sequenced, and genotyping was determined based on NS5 gene sequence. The differences in biochemical and blood routine indexes between HIV patients co-infected with different HCV genotypes and low/high viral loads were analyzed. Results A total of 126 HIV/HCV co-infected patients were collected, including 20 HCV genotype 1 (15.9%), 91 HCV genotype 3 (72.2%), and 15 HCV genotype 6 (11.9%). The maximum and minimum viral load of the three HCV genotypes were as follows: HCV type 1 (1.0×108, 4.8×104 IU/mL), HCV type 3 (2.2×108, 2.9×102 IU/mL), and HCV type 6 (8.1×107, 6.8×104 IU/mL). The results showed that there was no significant difference between HIV co-infection with different genotypes of HCV and three HIV treatment schemes, including nucleoside reverse transcriptase inhibitors+integrase strand transfer inhibitors (NRTIs+INSTIs), nucleoside reverse transcriptase inhibitors+non-nucleoside reverse transcriptase inhibitors (NRTIs+NNRTIs) and nucleoside reverse transcriptase inhibitors+protease inhibitor (NRTIs+PLs), and the viral load of patients (P>0.05). The analysis of biochemical indexes such as total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA), and blood routine indexes such as white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), platelet (PLT), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) among different HCV genotypes and low/high viral loads showed that there was no significant difference in biochemical indexes and blood routine indexes between low/high viral loads of HIV co-infected HCV patients (P>0.05); however, the biochemical indicators TBIL, IBIL and MCHC were significantly different statistically between patients with genotype 3 HCV infection and those with genotype 1 HCV infection (P<0.05), while other biochemical and blood routine indexes were not statistically different among different HCV genotypes (P>0.05). Conclusions There are six subtypes of HCV co-infection in HIV patients in Kunming, Yunnan Province, including three genes of genotype 1, 3, and 6. Among them, genotype 3 HCV is the main prevalent genetic virus among HIV co-infected populations. The TBIL, IBIL and MCHC values of HIV patients co-infected with HCV type 3 are different from those infected with HCV type 1.
6.Effects of electroacupuncture on gut microbiota and related inflammatory factors in rats with Crohn disease
Qiong LIU ; Haolong HE ; Jingjing YANG ; Sihui CAO ; Lin CHEN ; Jingying ZHOU ; Xia LIU ; Zongbao YANG ; Mi LIU
Journal of Acupuncture and Tuina Science 2024;22(1):12-21
Objective:To observe the effects of electroacupuncture(EA)on gut microbiota and serum inflammatory factors interleukin(IL)-1β and tumor necrosis factor(TNF)-α in Crohn disease(CD)model rats. Methods:Thirty-six Sprague-Dawley rats were randomly divided into a normal control(NC)group with 10 rats and a modeling group with 26 rats.In the modeling group,the CD rat model was prepared with 2,4,6-trinitrobenzene sulfonic acid(TNBS)enema.After successful modeling,the rats were randomly divided into a CD model(CD)group,an EA group,and a Western medicine(WM)group.The NC and CD groups received no treatment;the EA group was treated with EA for 20 min each time,with 7 consecutive days'intervention;the WM group received mesalazine enteric-coated tablet solution by gavage once a day for 7 d.The changes in body mass and disease activity index(DAI)were observed.Serum IL-1β and TNF-α were determined by enzyme-linked immunosorbent assay.Hematoxylin-eosin staining was used to observe the pathological changes of colon tissues,and 16S rDNA sequencing was used to analyze the structural changes of gut microbiota. Results:Compared with the NC group,the body mass of rats in the CD group decreased(P<0.01),and the DAI score increased(P<0.01);the colon tissue structure was disordered,and many inflammatory cells were present;also,IL-1β and TNF-α increased significantly(P<0.01).As a result,the diversity of gut microbiota decreased,and the abundance of some conditional pathogenic bacteria(such as Prevotella)increased,while the abundance of beneficial bacteria(such as Lactobacillus,Rochella,and Spirillum)decreased.After the intervention,compared with the CD group,the body mass of rats in the EA group and WM group increased(P<0.01);the DAI score decreased(P<0.01),the colon tissue structure improved,and the IL-1β and TNF-α levels decreased(P<0.01);the diversity of gut microbiota increased(P<0.05),and the abundance of some conditional pathogenic bacteria decreased while the abundance of beneficial bacteria increased in the EA group;whereas the diversity of gut microbiota in the WM group was not statistically different(P>0.05). Conclusion:EA can reduce the damage of colon mucosa,regulate the imbalance of gut microbiota,and inhibit the serum inflammatory factor IL-1β and TNF-α expression in CD rats.
7.Detection and In-house Quality Control Assessment for Cyclosporin A and Tacrolimus by High Performance Liquid Chromatography-tandem Mass Spectormetry Method
Like ZHONG ; Xiufang MI ; Qi SHU ; Gaoqi XU ; Chaoneng HE ; Junfeng ZHU
Herald of Medicine 2024;43(2):196-202
Objective To establish a quality control method for monitoring the blood concentrations of cyclosporin A and tacrolimus by HPLC-MS/MS,and to evaluate the quality control samples using the Westgard multi-rule theory.Methods HPLC-MS/MS was used to determine the concentration of cyclosporin A and tacrolimus in human whole blood.The quality control samples of low,medium and high concentration levels in the therapeutic drug monitoring process were statistically analyzed,Levery-Jennings and Z-score quality control charts were drawn,and the Westgard multi-rule theory was applied for in-house quality control evaluation.Results The established method was fully validated with linear ranges of 10.40-1 040.00 ng·mL-1 and 0.50-49.50 ng·mL-1,the quantification limits were 10.40 and 0.50 ng·mL-1,respectively.The extraction recoveries were 108.61%-113.24%and 101.99%-109.37%,respectively.The matrix factors normalized by internal standard were 106.68%-111.27%and 95.70%-97.81%for cyclosporin A and tacrolimus,respectively.The intra-day and inter-day accuracy and precision were less than 15.0%.Other parameters were also validated and met the acceptance criteria.Levery-Jennings and Z-score quality control charts showed that there were 4 warnings(violation of the 12s rule)in the results of the 26 groups of quality control samples in the third quarter of 2022,and no phenomenon was observed to be out of control.Conclusion The established in-house quality control system for therapeutic drug monitoring of cyclosporin A and tacrolimus can effectively ensure the accuracy of blood drug concentration detection.
8.Effect of Intraoperative Shaping,Screw Distribution,and Postoperative Healing on Plate Biomechanics
Wang ZHOU ; Jianqing XU ; Siyuan HE ; Shu ZHANG ; Junwen WANG ; Jing JIAO ; Bobin MI ; Guohui LIU ; Weiwei ZHU ; Zhisheng HE ; Liuyun ZHANG ; Mengxing LIU
Journal of Medical Biomechanics 2024;39(4):644-650
Objective To analyze the influence of shaping on the bending strength of bone plates and the influence of different locking nail distributions on plate force to provide biomechanical references for shaping plates and selecting different locking nail distributions.Methods Finite element simulation analysis of the four-point bending strength of a plate was performed according to the YY/T 0342-2020 standard.Theoretical analysis and finite element simulation method were used to analyze the force on prosthesis models with different lock-nail distributions.Results At 30° bending,the 3.7 mm-thick plate had 28%higher equivalent plastic strain than the 2.7 mm-thick plate.The 3.7 and 2.7 mm-thick plates had ultimate bending angles of 55° and 67°,respectively.The crease had little impact on the plate stress.The four-point bending strength and equivalent bending stiffness of the unshapeed structure were 2.64 N·m and 1.12 N·m2,respectively.The four-point bending strength and equivalent bending stiffness with the crease were 2.63 N·m and 1.10 N·m2,respectively.After forward and backward bending,the four-point bending strength of the plate decreased from 2.64 to 2.45 N·m by approximately 7.72%,and the equivalent bending stiffness decreased from 1.12 to 0.98 N·m2 by approximately 12%.The impact was obvious.After implantation of tamponade screws,the four-point bending strength of the single-hole plate improved significantly from 2.64 to 3.15 N·m,by approximately 19.32%and the equivalent bending stiffness increased from 1.12 to 1.14 N·m2,by approximately 2.1%.At least two locking holes were reserved on both sides of the fracture line.Not inserting the locking screw reduced the stress by approximately 50%compared with the full insertion of the locking screw.During 15-week postoperative walking without bone callus formation,the material stress of TC4 reached 852.7 MPa and yielding occurred.Conclusions In a clinical scenario where larger shaping is required,it is not suitable for plates with larger thicknesses and plate fractures are more likely to occur after large-thickness shaping.This can guide the clinical selection of plates with appropriate thickness based on the shaping angle,and tamponade screws can be implanted in extreme cases.Fixing locking screws clinically is recommended;however,a method of fixing the locking screws with full screws is not recommended.The biomechanical effect is best when two locking holes at both ends of the fracture line are maintained without fixing the locking screws.
9.Venetoclax combined with dose-reduced HAD as induction treatment for patients with de-novo acute myeloid leukemia
Zhangsong YAN ; Yang LI ; Bin ZHANG ; Jinsong HE ; Jiesi LI ; Shuning WEI ; Qi WANG ; Qiuling LI ; Kaiqi LIU ; Yingchang MI
Chinese Journal of Hematology 2024;45(4):387-390
The efficacy and safety of venetoclax combined with reduced dose HAD regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) was investigated. From May 2022 to January 2023, a total of 25 patients with newly diagnosed AML were treated with venetoclax combined with reduced-dose HAD regimen as induction therapy. Accoding to the 2017 ELN recommendations, 13 (52.0%) in favoable, 3 (12.0%) in intemediate, and 9 (36.0%) in adverse. The ORR (CR rate+PR rate) was 88.0%, and the CR rate was 84.0%. By May 30, 2023, with a median follow-up of 9 months, 1 year overall survival, event-free survival, and relapse-free survival were 100%, 94.7%, and 94.7%, respectively. All patients received 1-5 cycles of consolidation therapy and two median cycles. Treatment with venetoclax and reduced dose of HAD regimen in the treatment of patients with newly diagnosed AML was high effective and safe.
10.Modeling of medical equipment requirements for helicopter evacuation and rescue team based on AnyLogic
Shuo TANG ; Mi LI ; Li HE ; Bang-Fu ZHOU ; Liang ZHOU ; Nan XIAO ; Zhi-Gang ZHANG
Chinese Medical Equipment Journal 2024;45(5):28-33
Objective To provide references for reasonable equipping of airborne medical equipment oriented to different tasks by constructing a medical equipment requirement model for the helicopter evacuation and rescue team.Methods Relevant basic data were collected and organized on time for routine and emergency medical treatment and elementary medical equipment requirements for types of medical treatment.AnyLogic multi-agent modeling was used to established a medical equipment requirement model for the helicopter evacuation and rescue team,with the casualty,equipment and medical personnel as the agent modules and the logical relationship-based access rules between the agents.An example was taken with a Z-8 helicopter transformed into an ambulance platform to transport the rescue team and casualties,in which a variety of evacuation tasks with multi combinations of light and serious casualties were simulated and the model developed was used to record and analyze the data on waiting time for medical treatment,completion rate,personnel utilization rate and equipment requirement during 100 times of simulation flight.Results The model developed could provide generalized medical equipment allocation programs for the helicopter evacuation and rescue team to complete a variety of evacuation tasks in terms of electronic device,treatment equipment,auxiliary instrument and medical consumables.Conclusion The model developed facilitates rational allocation of medical equipment for the helicopter evacuation and rescue team.[Chinese Medical Equipment Journal,2024,45(5):28-33]

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