ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectiveTo explore the effects of Jingui Shenqiwan （JSW） and Liuwei Dihuangwan （LDW） on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group， the other six groups were as follows： a group of both males and females receiving JSW （3.0 g·kg^-1）， a group of both males and females receiving LDW （4.5 g·kg^-1）， a group of males receiving water and females receiving JSW， a group of males receiving water while females receiving LDW， a group of females receiving water while males receiving JSW， and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 （female∶male） ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth， which was followed by the observation of newborn mice， calculation of their average number， and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment， the weights of the thymus and spleen were measured to calculate the organ coefficients， and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems， while novel object recognition test （NOR） was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction （Real-time PCR） assay， and protein expression was analyzed with Western blot. ResultsCompared with the control group， oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together （P<0.05）， while LDW showed a trend but no statistical significance. Additionally， compared with the control group， JSW could upregulate the gene expression of gonadotropin-releasing hormone （GnRH） in the thalamus， as well as reproductive stem cell factor （SCF） and tyrosine kinase receptor （c-Kit） in the testes and reproductive stem cell marker mouse vasa homologue （MVH） in the ovaries， upregulate the expression of proteins influencing neuronal functional activity， such as brain-derived neurotrophic factor （BDNF）， in hippocampal neurons （P<0.05）， and enhance sucrose preference in male mice （P<0.05）. Compared with the control group， JSW significantly increased sucrose preference and novel object recognition index in offspring mice （P<0.05）， which was related to the upregulation of hippocampal dopamine D1 receptor （D1R） and N-methyl-D-aspartate receptor （Nmdar） gene expression. Compared with the control group， both JSW and LDW could upregulate the protein expression of glucocorticoid receptor （GR）， BDNF， and tyrosine kinase receptor B （TrkB） in the hippocampus of offspring mice （P<0.05）. ConclusionJSW significantly enhances the reproductive ability of normal mice， which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally， JSW has a certain regulatory effect on the brain function of the offspring mice.

ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.

ObjectiveThis study aims to investigate the effects of Linggui Zhugantang （LGZGT） on ventricular remodeling （VR） in mice with myocardial infarction （MI） and its impact on the Ras homologgene A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway. MethodsThe MI model of mice was established by ligating the left anterior descending coronary artery （LAD）. They were divided into the sham-operated group， the model group， the low-dose， medium-dose， and high-dose groups of LGZGT （2.34， 4.68， 9.36 g·kg^-1）， and the captopril group （3.25 mg·kg^-1）， with 10 mice in each group. After four weeks of continuous drug administration by gavage， the level of cardiac function in each group of mice was examined using small animal Doppler ultrasound. Hematoxylin-eosin （HE） staining and Masson staining was used to assess the morphological changes of myocardial tissue and calculate the rate of collagen fiber deposition in mouse myocardial tissue. Wheat germ agglutinin （WGA） staining was employed to compare the cross-sectional area of cardiomyocytes in each group of mice. The expression levels of α-smooth muscle actin （α-SMA）， matrix metalloproteinase-2 （MMP-2）， type Ⅰcollagen （Col Ⅰ）， Col Ⅲ， tissue inhibitor of metalloproteinase 1（TIMP1）， B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， Bcl-2， Caspase-3， and cleaved Caspase-3 were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to evaluate the mRNA levels of the pathway-related genes RhoA， ROCK1， and ROCK2. The protein expression levels of RhoA， ROCK1， and ROCK2 were tested by Western blot. ResultsThe level of cardiac function was markedly declined in the model group compared to the sham-operated group（P<0.01）. Myocardial tissue morphology changed significantly. The cross-sectional area of cardiomyocytes was significantly enlarged. The expression of α-SMA， MMP-2， Col Ⅰ， and Col Ⅲ was significantly upregulated（P<0.01）， and TIMP1 protein expression was significantly reduced（P<0.01）. The expressions of apoptosis-related proteins Bax were significantly up-regulated（P<0.01）， while the expression of Bcl-2 protein was significantly decreased（P<0.01）. The mRNA expression of RhoA， ROCK1， and ROCK2 were significantly upregulated （P<0.01）. Compared to the model group， the low-dose， medium-dose， and high-dose groups of LGZGT and the captopril group significantly reversed the experimental results of the model group in a dose-dependent manner （P<0.05， P<0.01）. ConclusionLGZGT significantly attenuated myocardial fibrosis， myocardial hypertrophy， and cardiomyocyte apoptosis after MI in mice and effectively reversed VR， the mechanism of which may be related to the modulation of the RhoA/ROCK signaling pathway.

ObjectiveThis study aims to investigate the effects of Linggui Zhugantang （LGZGT） on ventricular remodeling （VR） in mice with myocardial infarction （MI） and its impact on the Ras homologgene A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway. MethodsThe MI model of mice was established by ligating the left anterior descending coronary artery （LAD）. They were divided into the sham-operated group， the model group， the low-dose， medium-dose， and high-dose groups of LGZGT （2.34， 4.68， 9.36 g·kg^-1）， and the captopril group （3.25 mg·kg^-1）， with 10 mice in each group. After four weeks of continuous drug administration by gavage， the level of cardiac function in each group of mice was examined using small animal Doppler ultrasound. Hematoxylin-eosin （HE） staining and Masson staining was used to assess the morphological changes of myocardial tissue and calculate the rate of collagen fiber deposition in mouse myocardial tissue. Wheat germ agglutinin （WGA） staining was employed to compare the cross-sectional area of cardiomyocytes in each group of mice. The expression levels of α-smooth muscle actin （α-SMA）， matrix metalloproteinase-2 （MMP-2）， type Ⅰcollagen （Col Ⅰ）， Col Ⅲ， tissue inhibitor of metalloproteinase 1（TIMP1）， B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， Bcl-2， Caspase-3， and cleaved Caspase-3 were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to evaluate the mRNA levels of the pathway-related genes RhoA， ROCK1， and ROCK2. The protein expression levels of RhoA， ROCK1， and ROCK2 were tested by Western blot. ResultsThe level of cardiac function was markedly declined in the model group compared to the sham-operated group（P<0.01）. Myocardial tissue morphology changed significantly. The cross-sectional area of cardiomyocytes was significantly enlarged. The expression of α-SMA， MMP-2， Col Ⅰ， and Col Ⅲ was significantly upregulated（P<0.01）， and TIMP1 protein expression was significantly reduced（P<0.01）. The expressions of apoptosis-related proteins Bax were significantly up-regulated（P<0.01）， while the expression of Bcl-2 protein was significantly decreased（P<0.01）. The mRNA expression of RhoA， ROCK1， and ROCK2 were significantly upregulated （P<0.01）. Compared to the model group， the low-dose， medium-dose， and high-dose groups of LGZGT and the captopril group significantly reversed the experimental results of the model group in a dose-dependent manner （P<0.05， P<0.01）. ConclusionLGZGT significantly attenuated myocardial fibrosis， myocardial hypertrophy， and cardiomyocyte apoptosis after MI in mice and effectively reversed VR， the mechanism of which may be related to the modulation of the RhoA/ROCK signaling pathway.

With the rapid development of artificial intelligence, computational pathology has been seamlessly integrated into the entire clinical workflow, which encompasses diagnosis, treatment, prognosis, and biomarker discovery. This integration has significantly enhanced clinical accuracy and efficiency while reducing the workload for clinicians. Traditionally, research in this field has depended on the collection and labeling of large datasets for specific tasks, followed by the development of task-specific computational pathology models. However, this approach is labor intensive and does not scale efficiently for open-set identification or rare diseases. Given the diversity of clinical tasks, training individual models from scratch to address the whole spectrum of clinical tasks in the pathology workflow is impractical, which highlights the urgent need to transition from task-specific models to foundation models (FMs). In recent years, pathological FMs have proliferated. These FMs can be classified into three categories, namely, pathology image FMs, pathology image-text FMs, and pathology image-gene FMs, each of which results in distinct functionalities and application scenarios. This review provides an overview of the latest research advancements in pathological FMs, with a particular emphasis on their applications in oncology. The key challenges and opportunities presented by pathological FMs in precision oncology are also explored.
Humans ; Precision Medicine/methods* ; Medical Oncology/methods* ; Artificial Intelligence ; Neoplasms/pathology* ; Computational Biology/methods*

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Aim To explore the effects of D-limonene on the steatosis of primary mouse hepatocytes and its potential mechanism of action.Methods Oleic acid-induced steatosis in primary mouse hepatocytes was used as a model to observe the effects of D-limonene on cell viability,cellular lipid content,and intracellular expression of proteins such as AMP-activated protein kinase(AMPK),acetyl-coenzyme A carboxylase 1(ACC1),and carnitine palmitoyl transferase 1A(CPT1A).Results It was found that a low dose of D-limonene could effectively enhance the viability of primary mouse hepatocytes.When oleic acid at a con-centration of 300 μmol·L-1 successfully induced steatosis in primary mouse hepatocytes,D-limonene re-duced the lipid content of the cells,and D-limonene up-regulated the cellular AMPK expression level,down-regulated the cellular ACC1 and fatty acid synthetase(FAS)expression levels,which in turn promoted the overexpression of CPT1A.Conclusions D-limonene has the effect of reducing lipid deposition in primary mouse hepatocytes,and the mechanisms may be related to the activation of AMPK,the inhibitions of ACC1 and FAS,and the up-regulation of CPT1A protein expres-sion level.

Objective:To investigate the association between homocysteine (Hcy) and recurrent pregnancy loss (RPL), as well as its impact on clinical pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:This retrospective cohort study collected clinical data from patients undergoing IVF/ICSI-ET at the Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between December 2020 and March 2024. Patients were divided into no history of pregnancy loss group (named control group, n=1 027) and RPL group ( n=743) based on history of pregnancy loss. Peripheral blood Hcy levels were compared between the two groups. Multivariate logistic regression was performed to adjust for confounding factors and determine whether Hcy is an independent risk factor for RPL. RPL patients were divided into four subgroups based on Hcy quartiles, named Q1 subgroup (Hcy<7.03 μmol/L), Q2 subgroup (7.03 μmol/L≤Hcy<8.63 μmol/L), Q3 subgroup (8.63 μmol/L≤Hcy<10.44 μmol/L), and Q4 subgroup (Hcy≥10.44 μmol/L), to further analyze the impact of Hcy level on pregnancy outcomes after IVF/ICSI-ET in these patients. Results:1) Baseline characteristics between control and RPL groups: statistically significant differences were observed in female age, male age, female body mass index (BMI), duration of infertility, cause of infertility, and peripheral blood Hcy levels (all P<0.05). 2) After adjusting for female age, male age, female BMI, duration of infertility, and cause of infertility via multivariate logistic regression, elevated Hcy levels was identified as an independent risk factor for RPL (a OR=1.366, 95% CI: 1.298-1.438, P<0.001). 3) Baseline characteristics of the four RPL subgroups: antral follicle count (AFC) differed significantly among Q1, Q2, Q3 and Q4 subgroups [17.00 (11.00, 24.00), 15.00 (10.00, 24.00), 14.00 (7.00, 22.25), 15.50 (8.00, 22.00), P=0.043]. No statistically significant differences were observed in other baseline characteristics (all P>0.05). 4) Pregnancy outcomes across the four RPL subgroups: miscarriage rates in the Q1, Q2, Q3 and Q4 subgroups were 18.18% (18/99), 30.61% (30/98), 33.70% (31/92), and 35.96% (32/89), respectively, live birth rates were 44.26% (81/183), 36.17% (68/188), 32.80% (61/186), and 30.65% (57/186), respectively. Intergroup differences in miscarriage rate and live birth rate were statistically significant ( P=0.033, P=0.036). Specifically, miscarriage rate in the Q3 and Q4 subgroups, and live birth rate in the Q4 subgroup were significantly higher than those in the Q1 subgroup (all q<0.05). However, no significant differences were observed in clinical pregnancy rate or early miscarriage rate among the four groups (all P>0.05). After adjusting for confounding factors using multivariate logistic regression, taking the Q1 subgroup as the control, there were no statistically significant differences in the clinical pregnancy rate between the remaining groups and the Q1 subgroup (all P>0.05). The early miscarriage rate in the Q3 subgroup (a OR=2.184, 95% CI: 1.077-4.426, P=0.030) and the early miscarriage rate in the Q4 subgroup (a OR=2.290, 95% CI: 1.116-4.697, P=0.024) were significantly higher than those in the Q1 subgroup; the miscarriage rate in the Q3 subgroup (a OR=2.207, 95% CI: 1.125-4.330, P=0.021) and the miscarriage rate in the Q4 subgroup (a OR=2.377, 95% CI: 1.209-4.674, P=0.012) were significantly higher than those in the Q1 subgroup; the live birth rate in the Q3 subgroup (a OR=0.615, 95% CI: 0.401-0.944, P=0.026) and the live birth rate in the Q4 subgroup (a OR=0.560, 95% CI: 0.364-0.863, P=0.009) were significantly lower than those in the Q1 subgroup. Conclusion:Elevated Hcy is a high-risk factor for RPL in IVF/ICSI-ET patients and may adversely affect pregnancy outcomes.