Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

Objective To investigate the expression and role of T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)in the pathogenesis of experimental autoimmune uveitis(EAU).Methods A total of 12 male C57BL/6J mice,aged 4 to 5 weeks,were selected and divided into the control group(n=3)and the experimental group(n=9)using a random number table.The control group(modeling time point:0 days after modeling)received no treatment,while the experimental group was induced to establish an EAU model(divided into three subgroups according to the modeling time points:7 days,14 days,and 21 days after modeling,with 3 mice in each subgroup).Firstly,the interphotoreceptor retinoid-binding protein 651-670 and complete Freund's adjuvant were fully mixed and emulsified.Then,the emulsion was subcutaneously injected into the two thighs,tail base,and neck of mice in the experimental group(each mouse received 200 μL of immune emulsion containing 500 pg of interphotoreceptor retinoid-binding protein 651-670).Subsequently,each mouse in the experimental group was also intraperitoneally injected with 1 μg of pertussis toxin.The anterior segment and fundus of mice in each group were observed and photographed under a slit-lamp microscope.The clinical and histopatho-logical scoring of these mice was conducted according to the Caspi grading scale based on the severity of inflammation.The serum levels of IFN-γ and IL-17 were measured using the enzyme-linked immunosorbent assay(ELISA),while the mRNA expression of Tim-3 in the spleen and ocular tissues was detected using the real-time quantitative polymerase chain reaction(RT-qPCR).Western blot was employed to detect the protein expression of Tim-3,and immunohistochemistry was used to examine the protein expression of Tim-3 in the spleen tissue.Statistical analysis was performed using GraphPad Prism 9.0.Results The clinical scores of the anterior segment,fundus,and histopathology of the mice increased over time after modeling,with statistically significant differences among these groups(P＜0.05).The serum levels of IFN-γ and IL-17 in the mice also increased over time after modeling,with statistically significant differences among these groups(P＜0.05).The relative mRNA expression of Tim-3 in the spleen and ocular tissues of the mice decreased over time after modeling,with statistically significant differences among these groups(P＜0.05).The protein expression of Tim-3 in the ocular and spleen tissues showed the same pattern as its mRNA expression.Conclusion The expression of Tim-3 decreases with the exacerbation of inflammation in the progression of EAU,suggesting that Tim-3 may play a negative immunoregulatory role in the development of uveitis.

Objective To explore the technical advantages and applicable scenarios of surgical robot-assisted versus conventional freehand minimally invasive surgery for pelvic fractures by comparing clinical indicators,thereby providing evidence for clinical decision-making.Methods A retrospective case-control study was conducted on 59 patients with pelvic fractures treated with minimally invasive internal fixation between January 2022 and December 2024.Patients were divided into a conventional group(26 cases)and a robot-assisted navigation group(33 cases)based on the surgical technique.Pre-and postoperative pelvic computed tomography(CT)scans were performed,and anteroposterior,outlet,and inlet view radiographs were obtained.The maximum residual displacement after pelvic reduction and screw placement accuracy were measured based on radiographic and CT imaging.Intraoperative fluoroscopy frequency,radiation dose,operative time,blood loss,number of implanted screws,maximum residual displacement after reduction,and screw accuracy were recorded.Results No significant differences were observed between the two groups in age,gender,injury mechanism,or fracture classification,indicating comparability.Blood loss and fracture reduction quality showed no significant differences.The operative time was 52.5(30.8,62.3)min in the conventional group and 60(50,82.5)min in the robot-assisted group.Intraoperative fluoroscopy frequency and radiation dose were(19.1±5.4)times and 33.1(27.5,43.9)mGy in the conventional group,compared to(12.1±4.9)times and 123.1(101.1,131.4)mGy in the robot-assisted group.The robot-assisted group demonstrated superior screw placement accuracy,increased utilization of anterior column screws,and shorter postoperative ambulation time.Conclusion Robot-assisted minimally invasive surgery for pelvic fractures significantly outperforms conventional freehand techniques in improving screw placement accuracy and reducing radiation exposure for surgeons.It represents a preferable option for treating unstable pelvic fractures.

Objective To explore the technical advantages and applicable scenarios of surgical robot-assisted versus conventional freehand minimally invasive surgery for pelvic fractures by comparing clinical indicators,thereby providing evidence for clinical decision-making.Methods A retrospective case-control study was conducted on 59 patients with pelvic fractures treated with minimally invasive internal fixation between January 2022 and December 2024.Patients were divided into a conventional group(26 cases)and a robot-assisted navigation group(33 cases)based on the surgical technique.Pre-and postoperative pelvic computed tomography(CT)scans were performed,and anteroposterior,outlet,and inlet view radiographs were obtained.The maximum residual displacement after pelvic reduction and screw placement accuracy were measured based on radiographic and CT imaging.Intraoperative fluoroscopy frequency,radiation dose,operative time,blood loss,number of implanted screws,maximum residual displacement after reduction,and screw accuracy were recorded.Results No significant differences were observed between the two groups in age,gender,injury mechanism,or fracture classification,indicating comparability.Blood loss and fracture reduction quality showed no significant differences.The operative time was 52.5(30.8,62.3)min in the conventional group and 60(50,82.5)min in the robot-assisted group.Intraoperative fluoroscopy frequency and radiation dose were(19.1±5.4)times and 33.1(27.5,43.9)mGy in the conventional group,compared to(12.1±4.9)times and 123.1(101.1,131.4)mGy in the robot-assisted group.The robot-assisted group demonstrated superior screw placement accuracy,increased utilization of anterior column screws,and shorter postoperative ambulation time.Conclusion Robot-assisted minimally invasive surgery for pelvic fractures significantly outperforms conventional freehand techniques in improving screw placement accuracy and reducing radiation exposure for surgeons.It represents a preferable option for treating unstable pelvic fractures.

Objective To investigate the expression and role of T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)in the pathogenesis of experimental autoimmune uveitis(EAU).Methods A total of 12 male C57BL/6J mice,aged 4 to 5 weeks,were selected and divided into the control group(n=3)and the experimental group(n=9)using a random number table.The control group(modeling time point:0 days after modeling)received no treatment,while the experimental group was induced to establish an EAU model(divided into three subgroups according to the modeling time points:7 days,14 days,and 21 days after modeling,with 3 mice in each subgroup).Firstly,the interphotoreceptor retinoid-binding protein 651-670 and complete Freund's adjuvant were fully mixed and emulsified.Then,the emulsion was subcutaneously injected into the two thighs,tail base,and neck of mice in the experimental group(each mouse received 200 μL of immune emulsion containing 500 pg of interphotoreceptor retinoid-binding protein 651-670).Subsequently,each mouse in the experimental group was also intraperitoneally injected with 1 μg of pertussis toxin.The anterior segment and fundus of mice in each group were observed and photographed under a slit-lamp microscope.The clinical and histopatho-logical scoring of these mice was conducted according to the Caspi grading scale based on the severity of inflammation.The serum levels of IFN-γ and IL-17 were measured using the enzyme-linked immunosorbent assay(ELISA),while the mRNA expression of Tim-3 in the spleen and ocular tissues was detected using the real-time quantitative polymerase chain reaction(RT-qPCR).Western blot was employed to detect the protein expression of Tim-3,and immunohistochemistry was used to examine the protein expression of Tim-3 in the spleen tissue.Statistical analysis was performed using GraphPad Prism 9.0.Results The clinical scores of the anterior segment,fundus,and histopathology of the mice increased over time after modeling,with statistically significant differences among these groups(P＜0.05).The serum levels of IFN-γ and IL-17 in the mice also increased over time after modeling,with statistically significant differences among these groups(P＜0.05).The relative mRNA expression of Tim-3 in the spleen and ocular tissues of the mice decreased over time after modeling,with statistically significant differences among these groups(P＜0.05).The protein expression of Tim-3 in the ocular and spleen tissues showed the same pattern as its mRNA expression.Conclusion The expression of Tim-3 decreases with the exacerbation of inflammation in the progression of EAU,suggesting that Tim-3 may play a negative immunoregulatory role in the development of uveitis.

Objective To investigate the mechanism and clinical significance of miR-18a-5p and retinoid acid receptor-related orphan receptor-α(RORA)in the proliferation and progression of colorectal cancer(CRC)cells.Methods The expressions of miR-18a-5p and RORA in CRC cells and tissues were detected via qRT-PCR,FISH,and IHC.Cell proliferation capability was detected through EdU and CFSE assay,cell apoptosis by flow cytometry assay,and cell migration and invasion abilities by cell scratch and Transwell invasion assays,respectively.The targeted regulation of miR-18a-5p on RORA was further verified via dual-luciferase reporter assay,cell function rescue test,RT-PCR,and Western blot assay.Finally,bioinformatics was used to explore the molecular mechanism of miR-18a-5p promoting malignant proliferation,invasion,and progression of CRC via regulating RORA.Results miR-18a-5p exhibited a high expression in CRC tissues and cells(P<0.05)and promoted the proliferation,migration,and invasion of CRC cells(P<0.05).In addition,RORA served as the target gene of miR-18a-5p,and its overexpression effectively reduced the promoting function of miR-18a-5p in the malignant biological phenotype of CRC cells(P<0.05).The expression of RORA in CRC tissues showed a significantly positively correlation with the infiltration of CD8+T cells and the expression of its surface marker protein CD8A.Conclusion The targeted regulation of RORA by miR-18a-5p promotes the proliferation and progression of CRC.The miR-18a-5p/RORA regulatory pathway possibly contributes to the immune microenvironment of CRC,which can be a potential therapeutic target for CRC.

Objective To explore the effect and possible mechanism of petroleum ether extract from Gastrodia elata on A amyloid β-protein deposition in Caenorhabditis elegans(C.elegans).Methods C.elegans was used as the model organism,and the experiment was divided into blank group(Control group),GEPEE 0.5 mg·mL-1 group and GEPEE 1 mg·mL-1 group.The effects of GEPEE on paralysis,life span,oxidative stress,heat stress,reactive oxygen species(ROS)level and Aβ aggregation of C.elegans were investigated,qRT-PCR was used to detect the changes of gene expression related to insulin/IGF-1 signaling pathway(IIS)in C.elegans.The main components were analyzed by high performance liquid chromatography(HPLC).Results Compared with Control group,GEPEE could significantly improve the paralysis phenotype of C.elegans(P<0.01),prolong the lifespan of C.elegans(P<0.01),enhance the motility of C.elegans(P<0.01),and increased the resistance to external oxidative stress(P<0.01),the stress ability of high temperature(P<0.01),improved the deposition of Aβ in vivo(P<0.01),decreased the ROS content in C.elegans(P<0.01),decreased the expression levels of Aβ and DAF-2(P<0.01),increased the expression levels of DAF-16 and its target genes SOD-3,GSH-Px,HSF-1 and its target gene HSP-16.2,SKN-1 and its target gene GST-4(P<0.01).Its main components were p-hydroxybenzyl alcohol and p-ethoxylbenzyl alcohol by HPLC.This study showed that GEPEE can reduce Aβ-induced toxicity in CL4176 C.elegans by reducing ROS level in vivo,increasing antioxidant level and regulating IIS pathway.Conclusion GEPEE can inhibit the toxicity of Aβ protein,and its mechanism is related to the regulation of IIS signaling pathway.

Objective:To evaluate the role of ketamine in postoperative cognitive dysfunction (POCD) and to clarify the association with subdiaphragmatic vagus nerve in mice.Methods:One hundred and forty-four SPF healthy male C57BL/6J mice, aged 18 months, weighing 32-35 g, were divided into 8 groups ( n=18 each) using a random number table method: sham operation group (group C), surgery group (group S), ketamine + surgery group (group SK), ketamine + surgery + subdiaphragmatic vagotomy group (group SK+ SDV), pseudo germ-free mice+ normal saline group (group GM+ V), pseudo germ-free mice that received fecal microbiota transplantation (FMT) from group S mice group (group GM+ S), pseudo germ-free mice that received FMT from group SK mice group (group GM+ SK), and pseudo germ-free mice received subdiaphragmatic vagotomy and FMT from group SK mice group (group GM+ SDV+ SK). Tibial fracture internal fixation was performed under anesthesia with 2.0% isoflurane. Ketamine 50 mg/kg was intraoperatively administered at the beginning of the suture in group SK. The fecal samples were collected at 24 h after surgery to prepare fecal bacteria filtrate in S and SK groups. The dorsal and ventral branches of subdiaphragmatic vagus nerve were cut prior to ketamine administration in SK+ SDV group and prior to FMT in GM+ SDV+ SK group. Broad-spectrum antibiotics dissolved in drinking water were given ad libitum to mice for 14 consecutive days at 2 weeks before FMT or subdiaphragmatic vagotomy and replaced once every 2 days to establish the pseudo germ-free model. Pseudo germ-free mice were gavaged with normal saline or fecal suspension 200 μl obtained from mice for 14 consecutive days at fixed time starting from 14 days after antibiotic intervention in GM+ SK and GM+ SDV+ SK groups. While normal saline was given instead for 14 consecutive days in GM+ V group. The fecal samples were collected after tibial fracture internal fixation or at 24 h after completion of FMT for 16S rRNA gene sequence analysis. The contents of interleukin-6 (IL-6), IL-17, tumor necrosis factor-alpha (TNF-α), IL-4 and IL-10 in the hippocampus were measured by enzyme linked-immuno-sorbent assay at 24 h after surgery or FMT. The spatial memory and learning ability was assessed by the Morris water maze test at 24 h after surgery or FMT. Results:Compared with group Sham, Simpson′s diversity index, Shannon index and Ace index were significantly decreased, the contents of IL-6, IL-17 and TNF-α were increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group S ( P<0.05). Compared with group S, Simpson′s diversity index, Shannon index and Ace index were significantly increased, the contents of IL-6, IL-17 and TNF-α were decreased, contents of IL-4 and IL-10 were increased, the escape latency in the training and testing phases and swimming distance were shortened, and the time spent in the target quadrant was prolonged in group SK ( P<0.05). Compared with group SK, Simpson′s diversity index, Shannon index and Ace index were significantly decreased, the contents of IL-6, IL-17 and TNF-α were increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group SK+ SDV ( P<0.05). Compared with group GM+ V, the contents of IL-6, IL-17 and TNF-α were significantly increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group GM+ S ( P<0.05). Compared with group GM+ S, the contents of IL-6, IL-17 and TNF-α were significantly decreased, contents of IL-4 and IL-10 were increased, the escape latency in the training and testing phases and swimming distance were shortened, and the time spent in the target quadrant was prolonged in group GM+ S ( P<0.05). Compared with group GM+ SK, the contents of IL-6, IL-17 and TNF-α were significantly increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group GM+ SDV+ SK ( P<0.05). Conclusions:Ketamine can improve intestinal flora disorders and reduce POCD in mice, and the mechanism may be related to subdiaphragmatic vagal nerve conduction.

Objective:To investigate the workflow, feasibility and advantages of respiratory navigator-guided stereotactic body radiation therapy (SBRT) of liver malignancies on the magnetic resonance linear accelerator (MR-linac).Methods:Clinical data of 10 patients with liver cancer treated with respiratory navigator-guided SBRT on the MR-linac from September to December 2021 were analyzed retrospectively. All patients underwent CT and MR simulated localization, and plain, enhanced and 4D CT scan, and T 1 3D MR and T 2 3D MR images were collected. The expiratory 4D CT was chosen to design the reference plan. The T 2 3D navigator MR image (end-exhalation) was collected before treatment, the target position was adjusted or the target shape was modified in combination with the real-time monitoring 2D MR image and appropriate online adaptive planning process was selected. Then, the ability of CT, T 2 3D and T 2 3D navigator MR images to display the tumor was evaluated by naked eye. The changes of target volume were calculated. Dosimetric differences between the adaptive and reference plans were compared. The efficacy and adverse reactions of patients were evaluated. Results:In the free breathing state, the T 2 3D navigator MR image was significantly better than T 2 3D MR image to clearly display the tumor and its boundary. The adaptive plans of adapt-to-position (ATP) and adapt-to-shape (ATS) adopted by 10 patients was 37 times and 22 times respectively. The tumor subsided significantly in 3 patients. The average target conformal index (CI) of the adaptive plans was no different from that of the reference plans, but the gradient index (GI) was higher ( P<0.05), especially in the ATS plans. Compared to the reference plans, the normal liver V 5 Gy, V 10 Gy and D mean were almost the same, but the average MU was increased with a significant difference in the ATP adaptive plans ( P<0.05). The average of MU, segments and normal liver D mean and V 10 Gy in the ATS adaptive plans were lower than those in the reference plans, and the liver V 5 Gy was slightly increased. Seven patients were evaluated after 1 month and 3 months. The local control of lesions was promising. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusion:Respiratory navigator on MR-linac improves the visual clarity of tumors and online MR images, and shows its advantages to guide the adaptive precision radiotherapy of liver tumors, especially in SBRT.

Objective:To investigate the safety and mid-term efficacy of robotic versus laparoscopic total mesorectal excision surgery in rectal cancer.Methods:A total of 240 patients were diagnosed with rectal cancer at the Anorectal Department of Gansu Provincial Hospital from Aug 2015 to Mar 2021, 112 patients underwent laparoscopic total mesorectal excision (L-TME group) and 128 patients did robotic-assisted total mesorectal excision (R-TME group).Results:Compared to the R-TME group, the L-TME group had higher conversion rate (5.4% vs. 0.8%, χ2=4.417, P=0.036), higher incidence of complications (32.1% vs. 17.2%, χ2=7.290, P=0.007), higher circumferential resection margin involvement (7.1% vs. 1.6%, χ2=4.658, P=0.031), lower 3-year DFS and OS(74.1% vs. 85.2%, χ2=4.962, P=0.026) and (81.3% vs. 91.4%, χ2=5.494, P=0.019), lower 3-year DFS and OS in AJCC stage Ⅲ(52.5% vs. 76.1%, χ2=5.799, P=0.016) and (65.0% vs. 84.8%, χ2=4.787, P=0.029). Conclusion:R-TME can achieve better oncological outcomes and is more beneficial for RC patients compared with L-TME, especially for those with stage Ⅲ rectal cancers.