Objective To investigate the causal relationship between metabolic syndrome and breast cancer by using a bidirectional two-sample Mendelian randomization (MR) approach. Methods Genome-wide association study (GWAS) summary statistics for metabolic syndrome and breast cancer were acquired from the Integrative Epidemiology Unit GWAS database and the GWAS Catalog, with populations encompassing the United States and East Asia. A bidirectional causal design was employed: a forward analysis with metabolic syndrome as the exposure and breast cancer as the outcome, followed by a reverse analysis wherein their roles were interchanged. The inverse-variance weighting (IVW) method was primarily used for effect estimation, supplemented by MR-Egger regression, the weighted median method, the simple mode method, and the weighted mode method. Instrument variable strength was screened using the F-statistic (F>10). Robustness of the results was assessed through heterogeneity tests, horizontal pleiotropy tests, forest plots, and leave-one-out sensitivity analyses. Results The IVW analysis indicated no significant causal relationship between metabolic syndrome and breast cancer (OR=1.00, 95%CI: 0.97-1.03), P>0.05). Sensitivity analyses yielded consistent results, suggesting the good robustness of the study findings. Conclusion This study found no evidence to support a causal relationship, either positive or negative, between metabolic syndrome and breast cancer.

ObjectiveTo delineate imaging findings using an imaging platform and investigate the correlation between MRI characteristics of spinal cord atrophy and clinical diagnosis in children with spinal cord injury (SCI). MethodsImaging data of 150 children with SCI admitted to Beijing Bo'ai Hospital, China Rehabilitation Research Center, from January, 2002 to March, 2024 were collected and imported into the imaging platform. The anteroposterior and transverse diameters of the middle part of the spinal cord at the cross-section with the most severe atrophy were measured, and the relevant indicators of the previous normal spinal cord segment were measured as controls; the radiomic features were extracted. Clinical data of the children including gender, age, cause of injury, sensory level, motor level, spinal cord injury level, injury severity and disease course were collected. ResultsSpinal cord atrophy was identified in 81 cases (54%), among which 78 cases (96%) were American Spinal Injury Association Impairment Scale (AIS) grade A and 3 cases (4%) were AIS grade C. The upper boundary of the spinal cord atrophy site strongly correlated with the injury level, motor level and sensory level (r > 0.8, P < 0.001). ConclusionMore than half of children with SCI may develop secondary spinal cord atrophy, the vast majority of whom suffer from complete spinal cord injury; the upper boundary of spinal cord atrophy is correlated with the injury level.

The blood-brain barrier （BBB） is a physical and biochemical barrier that precisely regulates brain homeostasis and plays a central role in controlling the transport of endogenous and exogenous drugs and related metabolites across the blood-brain interface. These functions of the BBB are mediated by its major components， including brain microvascular endothelial cells （BMECs）， tight junction protein complexes， and influx and efflux transporter proteins. One of the pathological features of ischemic stroke （IS） is BBB disruption， which plays an important role in the development of post-stroke brain injury and subsequent neurological dysfunction. Therefore， given the increasing incidence of IS， there is an urgent need to develop new therapeutic strategies to prevent BBB dysfunction and thereby protect injured brain tissue after IS. This study describes the pathological mechanisms by which BMEC injury after IS leads to BBB dysfunction and elucidates the association between BMECs and IS， including the regulation of apoptosis， autophagy， inflammatory responses， oxidative stress， neurotoxic effects， and cerebral edema. In addition， this article summarizes Chinese herbal medicines that may prevent and treat IS by targeting BMECs. These include monomeric compounds and single herbs such as flavonoids， glycosides， phenols， phthalides， terpenoids， and Styrax. Traditional Chinese medicine （TCM） compound formulas and preparations include oral formulations such as Buyang Huanwu decoction， Sailuotong， Naoxintong capsules， Dandeng Tongnao capsules， and Shexiang Tongxin dropping pills， as well as injectable preparations such as Tongluo Jiunao injection， Xingnaojing injection， Danshen polyphenolic acid for injection， Yiqi Fumai injection， and Shuxuetong injection. This study aims to explore the protective effects of TCM against IS through targeted regulation of BMEC function， providing new insights into the mechanisms of IS and endovascular therapeutic strategies.

ObjectiveTo investigate the chromosomal characteristics of blastocysts and pregnancy outcomes in patients with polycystic ovary syndrome （PCOS）， and to analyze the impact of PCOS on embryonic aneuploidy rate and the risk of miscarriage. MethodsThe retrospective cohort study was conducted on the preimplantation genetic testing（PGT） in the First Affiliated Hospital of Sun Yat-sen University， including cycles of PGT for aneuploidy（PGT-A） and PGT for monogenic disorders（PGT-M）. The 191 PCOS cycles（PCOS group） were matched with 564 control cycles（control group） using propensity score matching. The oocyte and embryo viability， chromosomal testing results of blastocysts， and cumulative clinical outcomes were compared between two groups. Subgroup analysis was performed by stratifying PCOS patients based on oocyte retrieval （＞20 vs. ≤20）. And the pregnancy outcomes after euploid embryo transfer were compared under different levels of ovarian response. ResultsPCOS group showed a significantly higher rate of aneuploidy per blastocyst compared to control group （21.8% vs. 19.0%， P=0.044）. Clinically， the overall miscarriage rate in the PCOS group was significantly higher than control group （17.2% vs. 10.3%， P=0.024）， even after euploid embryo transfer （17.2% vs. 10.0%， P=0.019）. In the PCOS subgroup with ＞ 20 oocytes ， the miscarriage rate following euploid embryo transfer was dramatically increased compared to control group （21.4% vs. 6.7%， P=0.001）， accompanied by higher risks of early miscarriage （15.7% vs. 5.7%， P=0.011）. Conversely， the PCOS subgroup with ≤ 20 oocytes showed outcomes comparable to control group. ConclusionsPatients with PCOS exhibit a significantly higher rate of blastocyst aneuploidy compared to the control group. Furthermore， PCOS is associated with a marked increase in miscarriage rates following blastocyst transfer， even with euploid embryos， particularly among patients with high ovarian response.

Objective:To compare the efficacy and clinical practicality of fluorescence in situ hybridization (FISH), thinprep cytology test (TCT), urine nuclear matrix protein 22 (NMP22) and urine cytology test in the diagnosis of upper tract urothelial carcinoma (UTUC). Methods:A retrospective analysis was conducted on the clinical data of 62 patients who underwent surgical treatment (biopsy or partial urothelial resection) for suspected UTUC in the Department of Urology, Peking University Third Hospital from January 2021 to December 2023, and received paraffin pathological diagnosis. Taking the pathological examination results as the diagnostic criteria, the sensitivity, specificity, Youden index, positive predictive value and negative predictive value of the four detection methods in the diagnosis of UTUC were calculated, and the cost-effectiveness analysis was performed. Combine the four detection methods in pairs, calculate the sensitivity, specificity and Youden index after the combination, and conduct a cost-effectiveness analysis. The comparison of sensitivity, specificity and Youden index of the four detection methods was conducted using Chi-test or Fisher exact probability method. The comparison between groups after pairwise combinations was also conducted using Chi-test or Fisher exact probability method. The receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated.Results:The sensitivity (81.1%, 77.4%) and Youden index (0.700, 0.774) of FISH group and TCT group were significantly higher than those of NMP22 group and urine cytology group (39.6%, 43.4%; 0.174, 0.434), and the differences were statistically significant ( P<0.008 3). There were no statistically significant in the specificity (88.9%, 100.0%, 77.8%, 100.0%), positive predictive value (97.7%, 100.0%, 91.3%, 100.0%) and negative predictive value (44.4%, 42.9%, 17.9%, 23.1%) of the four groups ( P>0.008 3). The cost-effectiveness of the FISH group (3 256.4) was significantly higher than that of the TCT group (409.4), the NMP22 group (398.2) and the urine cytology group (627.9). After being combined in pairs, the net sensitivity of NMP22+ urine cytology (45.3%) was significantly lower than that of FISH+ TCT(88.7%), TCT+ NMP22(81.1%), FISH+ NMP22(86.8%), FISH + urine cytology (84.9%), TCT+ urine cytology (86.8%), and the difference was statistically significant ( P<0.008 3). The net specificities of the above combinations were 77.8%, 88.9%, 77.8%, 88.9%, 100.0%, respectively, and the differences were not statistically significant ( P>0.008 3). The cost-effectiveness was 1 008.0, 3 393.5, 632.8, 3 345.0, 3 513.5, and 737.3, respectively. Conclusions:In the diagnosis of UTUC, TCT has the highest diagnostic efficacy and relatively low cost, and is recommended for widespread promotion and application in clinical practice. If the patients economic conditions permit, it is recommended to combine TCT with urine cytology.

Objective:Based on HyperArc stereotactic radiotherapy(SRT)technique,six-dimensional free bed combined with double mask fixation was used to treat intracranial tumors,and the positioning errors of within batch and between batches were analyzed,so as to provide basis for the accuracy of clinical treatment of this technique.Methods:A total of 13 patients with intracranial tumors who admitted to Peking Union Medical College Hospital from March to July 2023 were retrospectively selected,and they were treated by using HyperArc SRT technique.The validation images of cone-beam computed tomography(CBCT)of within batch and between batches during treatment were analyzed.The positioning errors of three translational direction[left and right(x),head and foot(y)and abdominal and dorsal(z)]and rotational direction were analyzed.The each positioning error was set as group A,and the remaining error after the positioning error was corrected through six-dimensional free bed was set as group B,and the error post treatment was set as group C.The difference between group B and group C was defined as the change of within batch.According to the margin formula,the positioning error of within batch was used to calculate the required range of margin.Results:Under the mode of six-dimensional free bed correction combined with double mask fixation,a total of 59 times of HyperArc SRT on head were performed.In the comparison of the average errors on the six-dimensional direction among groups A,B and C,the errors of group A on x direction and y direction were respectively(0.119±0.039)and(-0.133±0.047)cm,and the differences of them between group A and group B[(0.004±0.002)and(0.018±0.005)cm]were significant(t=2.890,-3.224,P<0.05).There were no significant differences on other directions between the two groups(P>0.05).The error of RX direction of group B was(0.033±0.021)°,and the difference of that between group B and group C[(0.122±0.045)°]was significant(t=-2.306,P<0.05),while there were no significant differences on other directions(P>0.05).In the margin of the design of the plan of intracranial tumors,the x,y and z directions were respectively 0.6,0.9 and 0.4 mm.Conclusion:In the radiotherapy of using HyperArc SRT technique for intracranial tumors,the use of six-dimensional free bed combined with double mask treatment can significantly shorten the margin,and ensure accurate irradiation for gross tumor volume(GTV)and simultaneously reduce the irradiation volume and dose of surrounding normal tissue.

The hemodynamics within the aortic lumen is highly complex,and the mechanical stimuli generated by blood flow play a crucial role in the occurrence and progression of aortic dilation disease.Endothelial cells,as key components of the vascular endothelium,respond precisely to microenvironmental changes caused by blood flow through mechanoreceptors,including ion channels,receptor tyrosine kinases,and membrane structures.These mechanoreceptors convert mechanical stresses into biochemical signals,thereby affecting the physiological functions and pathological changes of blood vessels.In recent years,significant advances have been made in understanding the mechanisms by which endothelial mechanoreceptors are involved in aortic dilation diseases.This review summarizes the research progress of mechanoreceptor-mediated endothelial cell function in regulating aortic dilation diseases and provides a perspective on future research directions,with the aim of offering new insights and potential targets for the development of clinical treatment strategies.

Objective To determine the effect of baicalein on high glucose-induced cardiac fibro-blast pyroptosis based on the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)pathway.Methods Rat cardiac fibroblasts were grouped into control,high glucose group,low-,medium-and high-dose baicalein(H-,M-and L-baicalein)groups,and H-baicalein+NLRP3 agonist(BMS-986299)group.Except for the control group,all other groups were cultured in DMEM medium containing 40 mmol/L glucose,then 12.5,25 and 50 μmol/L baicalein was added into the medium correspondingly,and 1 μmol/L BMS-986299 was used to treat the H-baicalein+NLRP3 agonist group.Lactate dehydrogenase(LDH)cytotoxicity assay were employed to detect cell cytotoxicity.qRT-PCR and Western blotting were performed to determine the expression of NLRP3,Caspase-1,and GSDMD at mRNA and protein levels.Results High glucose treatment induced more EdU positive cells,higher pyroptotic rate,stronger cytotoxicity,higher Col-Ⅰ and Col-Ⅲ contents,and enhanced mRNA and protein levels of NLRP3,Caspase-1 and GSDMD in comparison to the control group(P＜0.05).The H-baicalein+NLRP3 agonist group had more EdU positive cells(26.85±2.95 cells vs 15.43±1.82 cells,P＜0.05),higher pyroptotic rate[(33.45±4.02)％vs(17.34±2.15)％,P＜0.05],stronger cytotoxicity[(27.94±2.93)％vs(14.13±1.87)％,P＜0.05],and increased contents of Col-Ⅰ(107.58±13.39 ng/ml vs 58.73±8.36 ng/ml,P＜0.05)and Col-Ⅲ(118.43±13.95 ng/ml vs 68.74±8.57 ng/ml,P＜0.05),and enhanced expression of NLRP3,Caspase-1 and GSDMD at both mRNA and protein levels(P＜0.05)when compared with the H-baicalein group.Conclusion Baicalein inhibits high glucose-induced cardiac fibroblast pyroptosis by suppressing NLRP3/Caspase-1/GSDMD pathway.

Objective:To investigates the efficacy and safety of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in treating older patients(≥60 years old)with hematologic malignancies.Methods:We conducted a retrospective study involving 67 patients aged 60 years and above, diagnosed with malignant hematological diseases, who received allo-HSCT at the Clinical Research Centrer for Haematologic Diseases of the First Affiliated Hospital of Soochow University between June 2015 and March 2023.We collected pre-transplant data, including the patients' age, gender, pre-transplantation disease risk stratification, disease status, and the haematopoietic cell transplantation comorbidity index(HCT-CI). We retrospectively analyzed clinical data regarding treatment-related toxicity, infections, acute and chronic graft-versus-host disease(a/cGVHD), as well as recurrent and non-recurrent deaths, to estimate the overall survival(OS)rate and event-free survival (EFS)rate.Results:Sixty-seven patients were included in the study, comprising 55 males(82.1%)and 12 females(17.9%), with a median age of 63(61, 65) years .The cohort consisted of 42 cases of acute myeloid leukaemia, 22 cases of myelodysplastic syndromes, and 3 cases of acute lymphoblastic leukaemia.The Kaplan-Meier analysis showed that the 1-year OS and EFS rates were 62.9% and 59.2%, respectively, while the 2-year OS and EFS rates were 55.3% and 51.8%, respectively.The cumulative incidence of 1-year non-relapse mortality and relapse was 25.4% and 21.2%, respectively.A total of 13 patients developed grade Ⅱ-Ⅳ aGVHD, with a 1-year cumulative incidence of 22.0%, and 7 patients developed cGVHD requiring treatment.When stratified by age group, the OS rate was higher in patients aged 60~64 years compared to those aged ≥65 years; however, this difference was not statistically significant(Log-rank χ2=0.99, P=0.317). In contrast, when stratified by disease load, the OS rate was significantly higher in the complete remission(CR)group than in the non-CR group, with a statistically significant difference(Log-rank χ2=15.04, P<0.001). When stratified by donor type, the OS rate was higher in the human leukocyte antigens (HLA) allogeneic group compared to the haploinsufficiency group; however, the difference was not statistically significant(Log-rank χ2=2.71, P=0.100). Twenty-seven patients died at an average of 125 days (range 3-1 054 days) after HSCT.The causes of death included leukemia recurrence in 9 cases (33.3%), infection in 8 cases (29.6%), GVHD in 5 cases (18.5%), poor implantation in 3 cases (11.1%), multi-organ failure in 1 case (3.7%), and cerebrovascular accident in 1 case (3.7%). The results of multifactorial analysis indicated that a pre-transplant tumor load greater than 5% was an independent risk factor for OS after transplantation ( HR=4.59, 95% CI: 2.01-10.42, P<0.001)as well as for disease recurrence ( OR=13.11, 95% CI: 1.96-87.87, P=0.008). Additionally, the occurrence of infection was identified as an independent risk factor for non-recurrent death after transplantation( OR=3.95, 95% CI: 1.13 to 13.71, P=0.031). Conclusions:For patients aged 60 years or older with hematologic malignancies, HSCT can serve as a viable treatment option, particularly for those with refractory recurrence and high cytogenetic risk, as it has the potential to significantly enhance prognosis and increase both EFS and OS rates.

Objective:To investigate the effects and possible mechanisms of targeted inhibition of Polo-like kinase 1 (PLK1) on the proliferation, mitosis and apoptosis of cervical cancer cells.Methods:Logarithmically growing human cervical cancer cell lines HeLa and C-33A were selected, and cells treated with 10 and 20 nmol/L PLK1 inhibitor GSK461364 were used as different concentrations of GSK461364 groups, while cells not treated with GSK461364 were used as the control group. CCK-8 method was used to detect cell proliferation ability (represented by absorbance values at wavelength 450 nm), flow cytometry was used to detect chromosome ploidy (propidium iodide staining), mitochondrial membrane potential detected by flow cytometry was used to evaluate cell apoptosis status (JC-1 fluorescent probe, the cells where the JC-1 monomers emitting green fluorescence were located were apoptotic cells), and Western blotting was used to detect the expression levels of cell cycle and apoptosis-related proteins.Results:The results of CCK-8 method showed that the proliferation ability of HeLa cells was lower than that of the control group after 24 hours of treatment with 10 and 20 nmol/L GSK461364 and continued culture for 24, 48 and 72 hours without GSK461364. The proliferation ability of C-33A cells was lower than that of the control group after 24 hours of treatment with 10 and 20 nmol/L GSK461364 and continued culture for 48 and 72 hours without GSK461364, and the differences were statistically significant (all P < 0.05). The results of flow cytometry analysis showed that after 24 hours of treatment with GSK461364 and continued culture for 72 hours without GSK461364, the proportions of polyploid cell subpopulations in HeLa cells of the 10 and 20 nmol/L GSK461364 groups and the control group were (13.89±3.73)%, (12.30±5.49)% and (9.86±1.15)%, respectively, with no statistically significant difference ( F = 0.82, P > 0.05); the proportions of polyploid cell subpopulations in C-33A cells of the 10 and 20 nmol/L GSK461364 groups and the control group were (8.45±2.20)%, (11.06±2.53)% and (5.42±1.36)%, respectively, with statistically significant difference ( F = 5.46, P = 0.045). Among them, the proportion of polyploid cell subpopulations in the 20 nmol/L GSK461364 group was higher than that in the control group, with statistically significant differences ( t = 3.40, P = 0.027). The results of flow cytometry detection of mitochondrial membrane potential showed that after 24 hours of treatment with GSK461364 and continued culture for 72 hours without GSK461364, the proportions of apoptotic cells in HeLa cells of the control group, 10 nmol/L GSK461364 group and 20 nmol/L GSK461364 group were (3.96±2.28)%, (24.38±4.89)%, and (46.24±4.38)%, respectively, and the difference was statistically significant ( F = 83.18, P < 0.000 1), the proportion of apoptotic cells in the 10 and 20 nmol/L GSK461364 groups was higher than that in the control group, and the difference was statistically significant (both P < 0.01), and the proportion of apoptotic cells in the 20 nmol/L group was higher than that in the 10 nmol/L group ( t = 5.76, P = 0.005); the proportions of apoptotic cells in C-33A cells of the control group, 10 nmol/L GSK461364 group and 20 nmol/L GSK461364 group were (1.81±1.59)%, (5.22±1.57)% and (15.87±5.81)%, respectively, with statistically significant differences ( F = 12.49, P = 0.007), and the proportion of apoptotic cells in the 20 nmol/L group was higher than that in the 10 nmol/L group and the control group (both P < 0.05). The results of Western blotting analysis showed that after 24 hours of treatment with GSK461364 and continued culture for 72 hours without GSK461364, the relative expression levels of cleaved Caspase-9 and cleaved polyadenosine diphosphate-ribose polymerase in HeLa and C-33A cells treated with 10 and 20 nmol/L GSK461364 were higher than those in the control group, and the relative expression levels of cdc25c and phosphorylated cdc25c (Ser216) were lower than those in the control group, and the differences were statistically significant (all P < 0.05). Conclusions:Targeted inhibition of PLK1 can inhibit the proliferation activity of cervical cancer cells in vitro, induce cell mitotic cycle arrest, and promote cell apoptosis; these may be achieved by regulating cell cycle and apoptosis-related proteins.