Objective:To investigate the effect of age factor on glymphatic function in patients with Parkinson′s disease (PD) and its potential correlation with overall cognitive performance based on diffusion tensor imaging analysis along the perivascular space(DTI-ALPS) index.Methods:The study was cross-sectional. Clinical and imaging data of 77 PD patients (PD group) who attended the Provincial Hospital of Shandong First Medical University from October 2021 to June 2024 were retrospectively analyzed. In the same period, 30 healthy volunteers matched by age and gender were collected as the normal control (NC) group. All subjects underwent MRI scanning and DTI-ALPS index was calculated based on diffusion tensor imaging. Cognitive functions of 46 patients in the PD group were assessed using the mini-mental state examination (MMSE) and montreal cognitive assessment (MoCA) scores. Independent samples t-tests were used to compare the differences in DTI-ALPS index between the PD and NC groups. After adjusting for confounders, the relationship between DTI-ALPS and age was explored using partial correlation analyses, multiple linear regression models. A mediation model was further developed to explore the mediating effect of DTI-ALPS index between age and cognitive function scores. Results:The DTI-ALPS indices of PD and NC groups were 1.66±0.20 and 1.44±0.17, respectively, and the differences were statistically significant ( t=5.27, P<0.001). The age of patients in the PD group was negatively correlated with the DTI-ALPS index ( r=-0.54, P<0.001), and age (β=-0.467, P<0.001) was an independent influencer of DTI-ALPS index. The DTI-ALPS index was positively correlated with MMSE scores ( r=0.53, P<0.001) and positively correlated with MoCA scores ( r=0.56, P<0.001). The mediation model showed that the DTI-ALPS index fully mediated between age and MMSE scores and partially mediated between age and MoCA scores, with an effect share of 33.25%. Conclusion:Age is an independent risk factor for impaired glymphatic pathway in PD patients, and it may induce cognitive decline in PD patients by exacerbating glymphatic pathway impairment.

Objective:To explore brain MRI features of methylmalonic acidemia (MMA).Methods:This observational study retrospectively analyzed the clinical and imaging data of 123 patients with MMA diagnosed at Shandong Provincial Hospital Affiliated to Shandong First Medical University and Qilu Hospital of Shandong University from January 2010 to November 2022. The 123 patients were divided into 7 stages according to age of onset, neonatal period (0 to<1 month), infancy (1 month to<1 year), early childhood (1 to<4 years), preschool (4 to<7 years), school age (7 to<13 years), adolescent (13 to 17 years) and adult (>17 years). All patients underwent brain MRI scanning. The imaging performances were evaluated, including the number, location, morphology of the lesions.Results:Of the 123 patients, 40 were in the neonatal period, 29 in infancy, 13 in early childhood, 9 in preschool, 6 in school age, 13 in adolescence, and 13 in adulthood. The first symptoms of patients in the neonatal period were mainly digestive system abnormalities, such as difficulty in breastfeeding (37.5%, 15/40) and vomiting (25.0%, 10/40), with neurological symptoms gradually becoming the main manifestations from infancy. Seventy-three cases (59.3%) showed significant abnormalities on cranial MRI, including 17 cases with 33 foci in the neonatal period, 23 cases with 53 foci in infancy, 11 cases with 16 foci in early childhood, 2 cases with 2 foci in preschool, 3 cases with 7 foci in school age, 7 cases with 9 foci in adolescence, and 10 cases with 16 foci in adulthood. In neonatal period, the main manifestations were myelin dysplasia (18%,6/33), dilatation of the lateral ventricular system (18%,6/33), and pallidal bulb infarct foci (18%,6/33); in infancy, the main manifestations were hypoplasia or thinning of the corpus callosum (30%,16/53); in early childhood, the main manifestations were pallidal bulb infarct foci (38%,6/16); and the two MRI abnormalities in preschool were pallidum and thalamic infarct foci; in school age, the main manifestations were infarct foci in the chiasmatic nucleus (29%,2/7) and in the caudate nucleus (29%,2/7); in adolescence, the main manifestation was dilatation of the lateral ventricular system (33%,3/9); and in adulthood, the main manifestation was dilatation of the lateral ventricular system (19%,3/16).Conclusion:By staging the age of onset, it is found that the imaging manifestations of MMA patients show significant differences with age, suggesting that there is a dynamic nature of MMA damage to brain structures at different developmental stages.

Objective To explore the effectiveness and safety of transurethral thermal steam ablation for the treatment of benign prostatic hyperplasia(BPH)patients with high-grade and high-risk.Methods Clinical data of elderly BPH pa-tients with high-risk treated with transurethral water vapour thermal from February 2022 to January 2025 were retrospectively ana-lyzed.The operation time,intraoperative bleeding,the number of injections during surgery,postoperative indwelling urinary catheter time,and surgical complications were recorded.And the differences in the International Prostate Symptom Score(IPSS),Quality of Life Score(QOL),Maximum Urinary Flow Rate(Qmax),and Residual Volume of Urine(PVR)before and after 3 and 6 months of the operation were recorded respectively.Results All 30 cases were successfully completed with an operation time of(10.167±2.984)min,intraoperative bleeding of(1.600±1.133)mL,the number of injections during surgery(6.600±1.793).No case of transfusion occurred.And the mean postoperative indwelling urinary catheter time was(8.467±3.246)d.After 3 and 6 months of postoperative follow-up,the Qmax increased from the preoperative(3.463±2.503)mL/s to(10.177±1.625)mL/s and(11.747±1.888)mL/s.PVR decreased from preoperative(209.623±191.960)mL to(40.433±23.713)mL and(30.300±20.223)mL.IPSS score decreased from preoperative(29.533±4.216)to(15.067±3.183)and(12.100±3.546).And QOL score decreased from preoperative(5.033±0.718)to(2.600±0.814)and(2.367±0.850).There were significant differences in observational indexes before and after the operation(P＜0.05).There was no case of postoperative urinary incontinence or secondary bleeding.Conclusion Transurethral water vapour thermal therapy is safe and effective for the treatment of elderly BPH patients with high-risk.

Objective To explore the effectiveness and safety of transurethral thermal steam ablation for the treatment of benign prostatic hyperplasia(BPH)patients with high-grade and high-risk.Methods Clinical data of elderly BPH pa-tients with high-risk treated with transurethral water vapour thermal from February 2022 to January 2025 were retrospectively ana-lyzed.The operation time,intraoperative bleeding,the number of injections during surgery,postoperative indwelling urinary catheter time,and surgical complications were recorded.And the differences in the International Prostate Symptom Score(IPSS),Quality of Life Score(QOL),Maximum Urinary Flow Rate(Qmax),and Residual Volume of Urine(PVR)before and after 3 and 6 months of the operation were recorded respectively.Results All 30 cases were successfully completed with an operation time of(10.167±2.984)min,intraoperative bleeding of(1.600±1.133)mL,the number of injections during surgery(6.600±1.793).No case of transfusion occurred.And the mean postoperative indwelling urinary catheter time was(8.467±3.246)d.After 3 and 6 months of postoperative follow-up,the Qmax increased from the preoperative(3.463±2.503)mL/s to(10.177±1.625)mL/s and(11.747±1.888)mL/s.PVR decreased from preoperative(209.623±191.960)mL to(40.433±23.713)mL and(30.300±20.223)mL.IPSS score decreased from preoperative(29.533±4.216)to(15.067±3.183)and(12.100±3.546).And QOL score decreased from preoperative(5.033±0.718)to(2.600±0.814)and(2.367±0.850).There were significant differences in observational indexes before and after the operation(P＜0.05).There was no case of postoperative urinary incontinence or secondary bleeding.Conclusion Transurethral water vapour thermal therapy is safe and effective for the treatment of elderly BPH patients with high-risk.

Objective:To investigate the effect of age factor on glymphatic function in patients with Parkinson′s disease (PD) and its potential correlation with overall cognitive performance based on diffusion tensor imaging analysis along the perivascular space(DTI-ALPS) index.Methods:The study was cross-sectional. Clinical and imaging data of 77 PD patients (PD group) who attended the Provincial Hospital of Shandong First Medical University from October 2021 to June 2024 were retrospectively analyzed. In the same period, 30 healthy volunteers matched by age and gender were collected as the normal control (NC) group. All subjects underwent MRI scanning and DTI-ALPS index was calculated based on diffusion tensor imaging. Cognitive functions of 46 patients in the PD group were assessed using the mini-mental state examination (MMSE) and montreal cognitive assessment (MoCA) scores. Independent samples t-tests were used to compare the differences in DTI-ALPS index between the PD and NC groups. After adjusting for confounders, the relationship between DTI-ALPS and age was explored using partial correlation analyses, multiple linear regression models. A mediation model was further developed to explore the mediating effect of DTI-ALPS index between age and cognitive function scores. Results:The DTI-ALPS indices of PD and NC groups were 1.66±0.20 and 1.44±0.17, respectively, and the differences were statistically significant ( t=5.27, P<0.001). The age of patients in the PD group was negatively correlated with the DTI-ALPS index ( r=-0.54, P<0.001), and age (β=-0.467, P<0.001) was an independent influencer of DTI-ALPS index. The DTI-ALPS index was positively correlated with MMSE scores ( r=0.53, P<0.001) and positively correlated with MoCA scores ( r=0.56, P<0.001). The mediation model showed that the DTI-ALPS index fully mediated between age and MMSE scores and partially mediated between age and MoCA scores, with an effect share of 33.25%. Conclusion:Age is an independent risk factor for impaired glymphatic pathway in PD patients, and it may induce cognitive decline in PD patients by exacerbating glymphatic pathway impairment.

Objective:To explore brain MRI features of methylmalonic acidemia (MMA).Methods:This observational study retrospectively analyzed the clinical and imaging data of 123 patients with MMA diagnosed at Shandong Provincial Hospital Affiliated to Shandong First Medical University and Qilu Hospital of Shandong University from January 2010 to November 2022. The 123 patients were divided into 7 stages according to age of onset, neonatal period (0 to<1 month), infancy (1 month to<1 year), early childhood (1 to<4 years), preschool (4 to<7 years), school age (7 to<13 years), adolescent (13 to 17 years) and adult (>17 years). All patients underwent brain MRI scanning. The imaging performances were evaluated, including the number, location, morphology of the lesions.Results:Of the 123 patients, 40 were in the neonatal period, 29 in infancy, 13 in early childhood, 9 in preschool, 6 in school age, 13 in adolescence, and 13 in adulthood. The first symptoms of patients in the neonatal period were mainly digestive system abnormalities, such as difficulty in breastfeeding (37.5%, 15/40) and vomiting (25.0%, 10/40), with neurological symptoms gradually becoming the main manifestations from infancy. Seventy-three cases (59.3%) showed significant abnormalities on cranial MRI, including 17 cases with 33 foci in the neonatal period, 23 cases with 53 foci in infancy, 11 cases with 16 foci in early childhood, 2 cases with 2 foci in preschool, 3 cases with 7 foci in school age, 7 cases with 9 foci in adolescence, and 10 cases with 16 foci in adulthood. In neonatal period, the main manifestations were myelin dysplasia (18%,6/33), dilatation of the lateral ventricular system (18%,6/33), and pallidal bulb infarct foci (18%,6/33); in infancy, the main manifestations were hypoplasia or thinning of the corpus callosum (30%,16/53); in early childhood, the main manifestations were pallidal bulb infarct foci (38%,6/16); and the two MRI abnormalities in preschool were pallidum and thalamic infarct foci; in school age, the main manifestations were infarct foci in the chiasmatic nucleus (29%,2/7) and in the caudate nucleus (29%,2/7); in adolescence, the main manifestation was dilatation of the lateral ventricular system (33%,3/9); and in adulthood, the main manifestation was dilatation of the lateral ventricular system (19%,3/16).Conclusion:By staging the age of onset, it is found that the imaging manifestations of MMA patients show significant differences with age, suggesting that there is a dynamic nature of MMA damage to brain structures at different developmental stages.

BACKGROUND: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. METHODS: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). RESULTS: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. CONCLUSIONS A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans ; Female ; Breast Neoplasms/genetics* ; East Asian People ; Neoplasm Recurrence, Local/genetics* ; Breast ; Algorithms ; Chronic Disease ; Prognosis ; Tumor Microenvironment

The estimated new cases of breast cancer (BC) patients were 2.26 million in 2020, which accounted for 11.7% of all cancer patients, making it the most prevalent cancer worldwide. Early detection, diagnosis and treatment are crucial to reduce the mortality, and improve the prognosis of BC patients. Despite the widespread use of mammography screening as a tool for BC screening, the false positive, radiation, and overdiagnosis are still pressing issues that need to be addressed. Therefore, it is urgent to develop accessible, stable, and reliable biomarkers for non-invasive screening and diagnosis of BC. Recent studies indicated that the circulating tumor cell DNA (ctDNA), carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), extracellular vesicles (EV), circulating miRNAs and BRCA gene from blood, and the phospholipid, miRNAs, hypnone and hexadecane from urine, nipple aspirate fluid (NAF) and volatile organic compounds (VOCs) in exhaled gas were closely related to the early screening and diagnosis of BC. This review summarizes the advances of the above biomarkers in the early screening and diagnosis of BC.
Humans ; Female ; Biomarkers, Tumor ; Early Detection of Cancer ; Breast Neoplasms/diagnosis* ; Prognosis ; MicroRNAs/genetics*

To enhance recombinant protein production by CHO cells, We compared the impact of overexpression of metabolic enzymes, namely pyruvate carboxylase 2 (PYC2), malate dehydrogenase Ⅱ (MDH2), alanine aminotransferase Ⅰ (ALT1), ornithine transcarbamylase (OTC), carbamoyl phosphate synthetase Ⅰ (CPSⅠ), and metabolism related proteins, namely taurine transporter (TAUT) and Vitreoscilla hemoglobin (VHb), on transient expression of anti-hLAG3 by ExpiCHO-S. Overexpression of these 7 proteins could differentially enhance antibody production. OTC, CPSI, MDH2, and PYC2 overexpression could improve antibody titer by 29.2%, 27.6%, 24.1%, and 20.3%, respectively. Specifically, OTC and MDH2 could obviously improve early-stage antibody production rate and the culture period was shortened by 4 days compared with that of the control. In addition, OTC and MDH2 had little impact on the affinity of anti-hLAG3. In most cases, overexpression of these proteins had little impact on the cell growth of ExpiCHO-S. MDH2 and ALT1 overexpression in H293T cells could also improve antibody production. Overall, overexpression of enzymes involved in cellular metabolism is an effective tool to improve antibody production in transient expression system.
Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Enzymes/metabolism* ; Recombinant Proteins/genetics*

Bispecific antibody (BsAb) has two different antigen-binding sites, divided into the "IgG-like" format and the "non-IgG-like" format. Different formats have different characteristics and applications. BsAb has higher sensitivity and specificity than conventional antibodies, with special functions such as recruitment of immune cells and blocking of dual signaling pathways, playing an important role in immune-diagnosis and therapy. With the deterioration of the global environment and the irregular living habits of people, the incidence of tumor is becoming higher and higher. Tumor becomes the most serious fatal disease threatening human health after cardiovascular disease. There are 12 million estimated new tumor cases each year worldwide. The major clinical treatments of tumor are surgical resection, chemoradiotherapy, target therapy. Tumor immunotherapy is a novel approach for tumor treatment in recent years, and activates human immune system to control and kill tumor cells. Although the traditional monoclonal antibodies have already acquired some therapeutic effects in tumor targeted therapy and immunotherapy, they induce drug resistance resulted from the heterogeneity and plasticity of tumors. Binding to two target antigens at the same time, BsAb has been used in the clinical treatment of tumors and obtained promising outcomes. This review elaborates the research progress and applications of bispecific antibody in clinical tumor therapy.
Antibodies, Bispecific/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Humans ; Immunotherapy ; Neoplasms/therapy*