ObjectiveIn recent years, the negative impact of microgravity on astronauts’ nervous systems has received widespread attention. The repetitive transcranial magnetic stimulation (rTMS) technology has shown significant positive effects in the treatment of neurological and psychiatric disorders. The potential benefits of combined frequency stimulation (CFS) which combines different frequency stimulation patterns in ameliorating neurological dysfunctions induced by the microgravity environment, still require in-depth investigation. Exploring the therapeutic effects and electrophysiological mechanisms of CFS in improving various neurological disorders caused by microgravity holds significant importance for neuroscience and the clinical application of magnetic stimulation. MethodsThis study employed 40 C57BL/6 mice, randomly divided into 5 groups: sham group, hindlimb unloading (HU) group, 10 Hz group, 20 Hz group, and combined frequency stimulation (10 Hz+20 Hz, CFS) group. Mice in all groups except the sham group received 14 d of simulated microgravity conditions along with 14 d of repetitive transcranial magnetic stimulation. The effects of CFS on negative emotions and spatial cognitive abilities were assessed through sucrose preference tests and water maze experiments. Finally, patch-clamp techniques were used to record action potentials, resting membrane potentials, and ion channel dynamics of granule neurons in the hippocampal dentate gyrus (DG) region. ResultsCompared to the single-frequency stimulation group, behavioral results indicated that the combined frequency stimulation (10 Hz+20 Hz) significantly improved cognitive impairments and negative emotions in simulated microgravity mice. Electrophysiological experiments revealed a decrease in excitability of granule neurons in the hippocampal DG region after HU manipulation, whereas the combined frequency stimulation notably enhanced neuronal excitability and improved the dynamic characteristics of voltage-gated Na⁺ and K⁺ channels. ConclusionThe repetitive transcranial magnetic stimulation with combined frequencies (10 Hz+20 Hz) effectively ameliorates cognitive impairments and negative emotions in simulated microgravity mice. This improvement is likely attributed to the influence of combined frequency stimulation on neuronal excitability and the dynamic characteristics of Na⁺ and K⁺ channels. Consequently, this study holds the promise to provide a theoretical basis for alleviating cognitive and emotional disorders induced by microgravity environments.

Objective To compare the blood glucose control effect and safety between insulin degludec and insulin aspart and insulin aspart 30 in non-obese patients with type 2 diabetes mellitus(T2DM).Methods Non-obese patients with T2DM were divided into treatment group and control group according to different treatment methods.The control group was treated with insulin aspart 30,and the treatment group was treated with insulin degludec and insulin aspart.Pancreatic islet related indicators[fasting C-peptide(FCP)and 2-hour postprandial C-peptide(2 h CP)],blood glucose control effect[fasting blood glucose(FBG),2-hour postprandial blood glucose(2 h PG)and glycated hemoglobin(HbA1c)],serum 25-hydroxyvitamin D[25(OH)D]and the risk of hypoglycemia were compared between the two groups.Results There were 41 cases in treatment group and 39 cases in control group.After treatment,FCP levels in treatment group and control group were(0.84±0.09)and(1.07±0.14)nmol·L-1;2 h CP levels were(1.03±0.15)and(1.69±0.17)nmol·L-1;FBG levels were(5.46±0.57)and(6.18±0.67)mmol·L-1;2 h PG levels were(8.17±0.85)and(9.03±0.94)mmol·L-1;HbA1 c were(5.35±0.57)％and(6.47±0.68)％;25(OH)D levels were(26.33±2.75)and(20.54±2.17)nmol·L-1,all with significant difference(all P＜0.05).The incidence rates of non-severe hypoglycemia in treatment group and control group were 14.63％and 35.90％,with statistically significant difference(P＜0.05).The incidence rates of severe hypoglycemia in treatment group and control group were 9.76％and 12.82％;the incidence rates of nocturnal hypoglycemia were 19.51％and 17.95％,without statistically significant difference(all P＞0.05).Conclusion The overall therapeutic effect of insulin degludec and insulin aspart on non-obese patients with T2DM is better than that of insulin aspart 30.The former can effectively regulate blood glucose and pancreatic islet cell function,lower the risk of non-severe hypoglycemia.

ObjectiveAngle-closure glaucoma (ACG) is one of the major eye-blinding diseases. To diagnose ACG, it is crucial to examine the anterior chamber angle. Current diagnostic tools include slit lamp gonioscopy, water gonioscopy, ultrasound biomicroscopy (UBM), and anterior segment optical coherence tomography (AS-OCT). Slit lamp and water gonioscopy allow convenient observation of the anterior chamber angle, but pose risks of invasive operation and eye infections. UBM can accurately measure the structure of the anterior chamber angle. However, it is complex to operate and unsuitable for patients, who have undergone trauma or ocular surgery. Although AS-OCT provides detailed images, it is costly. The aim of this study is to explore a non-invasive, non-destructive optical reflection tomography (ORT) technique. This technique can achieve low-cost three-dimensional imaging and full-field anterior chamber angle measurement of the porcine eye. MethodsThe experiment involved assembling an optical reflection tomography system, which included a complementary metal oxide semiconductor (CMOS) camera, a telecentric system, a stepper motor, and a white light source, achieving a spatial resolution of approximately 8.5 μm. The process required positioning the porcine eye at the center of the field of the imaging system and rotating it around its central axis using a stepper motor. Reflection projection images were captured at each angle with an exposure time of 1.0 ms and an interval of 2°. The collected reflection-projection data were processed using a filtered reflection tomography algorithm, generating a series of two-dimensional slice data. These slices essentially represented cross-sectional views of the three-dimensional structural image, and were reconstructed into a complete three-dimensional structural image. Based on the reconstructed three-dimensional structural image of the porcine eye, the anterior chamber angles at different positions were measured, and a distribution map of these angles was drawn. Simultaneously, the ORT measurements were compared with the standard results obtained from optical coherence tomography (OCT) to assess the accuracy of ORT measurements. ResultsIn this study, we successfully obtained the reflection projection data of a porcine eye using ORT technology, reconstructed its three-dimensional structural image, and measured the anterior chamber angle, generating the corresponding distribution map. To better distinguish the different structural parts of porcine eye, the three-dimensional structural image was marked with blue, green, and yellow dashed lines from the outer to the inner layers. The area between the blue and green dashed lines corresponded to the sclera. The area between the green and yellow dashed lines corresponded to the iris. The area inside the yellow dashed line corresponded to the pupil. The three-dimensional structural image clearly revealed the key anatomical features of the porcine eye. It was able to measure the anterior chamber angle at different positions. Additionally, the anterior chamber angle measurements of the porcine eye using ORT were compared with the measurements obtained using a TEL320C1 type OCT system, showing an average deviation of 0.51° and a mean square error MSE of 0.317. ConclusionORT is a non-invasive, non-destructive, low-cost, and high-resolution imaging technique capable of achieving three-dimensional structural imaging and full-field anterior chamber angle measurement of a porcine eye. This technology offers a new perspective for the diagnosis of angle-closure glaucoma and is significant for the screening, diagnosis, and monitoring of eye diseases, potentially benefiting clinics and small hospitals in remote areas in the future.

Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P＜0.05 or P＜0.01 or P＜0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.

Objective To investigate the effectiveness of real-time tracking and virtual reality technology(RTVI)used to assist the intraoperative alignment of the trauma orthopaedic surgery robot for the treatment of femoral neck fractures and its impact on the treatment outcome.Methods A retrospective analysis was conducted on 60 patients with femoral neck fractures treated with trauma orthopedic robotic surgery from September 2020 to September 2022.Patients were divided into two groups according to whether RTVI technology was used during surgery to assist robotic surgery.There were 28 patients in the RTVI group(12 males and 16 females),with an average age of(46.2±9.3)years old ranging from 28 to 60 years old.There were 32 patients in the simple Tianji surgical robot group,including 15 males and 17 females,aged(48.2±7.8)years old ranging from 32 to 58.The number of registered fluoroscopy,operation time,total number of intraoperative fluoroscopy,intraoperative blood loss,and hospitalization time of the two groups of patients were observed and recorded.All patients received regular follow-up after surgery,and hip X-rays were routinely reviewed to record Garden alignment index,fracture healing time,postoperative complications,and Harris score.Results All 60 patients were followed up.The RTVI group was followed up for 9 to 16 months with an average of(13.0±l.2)months,and the Tianji surgical robot group alone was followed up for 10 to 14 months with an average of(12.0±1.3)months.During the follow-up period,the femoral neck fractures of both groups of patients healed well,and no complications such as internal fixation loosening and incision infection occurred.The number of registered fluoroscopy,operation time,and number of intraoperative fluoroscopy of patients in the RTVI group were significantly better than those in the simple Tianji surgical robot group(P＜0.01).There was no statistically significant difference in intraoperative blood loss,hospital stay,Garden alignment index,fracture healing time,and hip Harris score between two groups(P＞0.05).Conclusion Although RTVI technology assisted by the surgical robot for femoral neck fracture surgery has little impact on its postoperative outcome,it can effectively reduce the operating time,the number of intraoperative X-ray projections,and the risk of intraopera-tive radiation exposure to patients.It also shortened the learning curve of the operator and better reflected the precision and ef-ficiency of the trauma orthopaedic surgery robot.

[Objective] To analyze the correlation of serum creatinine (Cr), hemoglobin (HGB) and body mass index (BMI) with osteoporosis in middle-aged and elderly Tibetan residents in Xizang and its predictive value for osteoporosis. [Methods] Between November 2021 and August 2023, using multistage random cluster sampling method information on demographics, we collected blood indices and bone mineral density from 564 middle-aged and elderly Tibetan residents in Ali (Pulan, Zada, Ritu, and Rezhe counties), Nagchu (Nagchu, Nyima, Amdo, Shuanghu, and Bango counties), Shannan (Lunzi county), and Lhasa (Nimu county), Tibetan regions. They were divided into osteoporosis group (90 cases) and non-osteoporosis group (474 cases) according to whether they suffered from osteoporosis or not. Pearson correlation method was used to analyze the correlation between bone mineral density (BMD) and each variable. Binary Logistic regression was used to analyze the related influencing factors of osteoporosis in middle-aged and elderly Tibetan residents, and the regression equation model of predicting the risk factors of osteoporosis was constructed. The fitting degree of the model was tested by Hosmer-Lemeshow test model. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of serum Cr, HGB and BMI combined tests on osteoporosis in middle-aged and elderly Tibetan residents in Xizang. [Results] The prevalence of osteoporosis was higher in females than in males. Among the osteoporosis group, height and weight, alanine aminotransferase, glutamine aminotransferase, urea nitrogen, uric acid, total cholesterol, triglyceride, low-density lipoprotein cholesterol, homocysteine, serum Cr, HGB and BMI were significantly lower (P<0.05). Correlation analysis showed that age was negatively correlated with BMD, while body weight, serum Cr, HGB and BMI were positively correlated with BMD (P<0.05). Multivariate binary Logistic results showed that age (OR=1.085), serum Cr (OR=0.891), BMI (OR=0.475), and HGB (OR=0.966) were the influencing factors for the occurrence of osteoporosis (P<0.05). To establish a prediction model for the risk of osteoporosis, Logit(P)=6.265+ 0.086×age + (-0.109×Cr)+ (-0.020×HGB)+ (-0.213×BMI). The area under the ROC curve was 0.932, the sensitivity was 88.9%, and the specificity was 82.5%. Hosmer-Lemeshow test model had a good fit (P=0.960). According to Logit(P) model, L score=-29.413+ (-0.404×age)+ 0.512×Cr+ 0.094×HGB+ BMI could be calculated. When L score >8.9, the patient could be diagnosed with the disease. [Conclusion] The decrease in serum Cr, HGB and BMI is a risk factor for osteoporosis in Tibetan aged residents. Age was negatively correlated with BMD, while serum Cr, HGB and BMI were positively correlated with BMD. The combined model of age, serum Cr, HGB and BMI can significantly improve the diagnostic efficiency of osteoporosis in the elderly Tibetans in Xizang.

Objective:To explore the correlation between transcranial sonography (TCS) combined with serum homocysteine (Hcy), blood glucose, blood lipids, the cognitive status of Parkinson′s disease (PD) patients, and to analyze the clinical application value of these parameters in assessing the cognitive status of PD patients.Methods:A total of 152 PD patients admitted to the Second Affiliated Hospital of Soochow University from January 2020 to June 2023 were retrospectively collected as the PD group, and 101 healthy examinees matched for age and gender during the same period were selected as control group. Clinical data [age, gender, duration of illness, Montreal Cognitive Assessment (MoCA) score, Mini-Mental State Examination (MMSE) score, Unified Parkinson′s Disease Rating Scale Part Ⅲ (UPDRS-Ⅲ) score, Hoehn-Yahr (H-Y) stage, etc.], serum tests (Hcy, blood glucose, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein concentration), and TCS examination results (third ventricular width, midbrain area, peak systolic velocity of bilateral middle cerebral arteries, bilateral middle cerebral artery resistance index, bilateral substantia nigra hyperechoic area) were collected. The two groups were divided into pure PD group and PD group with elevated Hcy, pure control group and control group with elevated Hcy, based on an Hcy concentration threshold of ≥15 μmol/L. The differences in the above parameters among the four groups were compared. The correlation between Hcy and cognitive status (MoCA score, MMSE score) of PD patients and the above parameters were analyzed.Results:The MoCA score and MMSE score of the PD group with elevated Hcy were lower than those of the pure PD group, and the UPDRS-Ⅲ score and H-Y stage were higher than those of the pure PD group (all P<0.001). The order of Hcy concentration from high to low was PD group with elevated Hcy, pure Hcy elevation group, pure PD group, and pure control group. The differences in serum data and TCS data among the four groups were statistically significant (all P<0.001). Spearman correlation analysis showed: ①In the PD group, the concentration of Hcy was positively correlated with glucose concentration, H-Y stage, low-density lipoprotein concentration, right middle cerebral artery resistance index, UPDRS-Ⅲ score, total cholesterol concentration, triglyceride concentration, left middle cerebral artery resistance index, third ventricular width, and age ( rs=0.422, 0.350, 0.348, 0.334, 0.325, 0.300, 0.293, 0.283, 0.221, 0.164, all P<0.05); Hcy concentration was negatively correlated with midbrain area, MMSE score, MoCA score, peak systolic velocity of right middle cerebral artery, peak systolic velocity of left middle cerebral artery, and high-density lipoprotein concentration ( rs=-0.328, -0.282, -0.245, -0.229, -0.224, -0.192, all P<0.05). ②Clinical data, serum data, and TCS data of PD patients were all correlated with MoCA score and MMSE score, with midbrain area showing the largest positive correlation ( rs=0.524, 0.516; both P<0.05) and H-Y stage showing the largest negative correlation( rs=-0.490, -0.468; both P<0.05). Conclusions:PD patients with elevated Hcy have lower cognitive scores than pure PD patients. The correlation between Hcy concentration and blood glucose concentration is the highest in PD patients, followed by H-Y stage. The cognitive scores of PD patients are most correlated with midbrain area and unrelated to substantia nigra hyperechoic area. Lowering serum Hcy concentration in PD patients may be one of the ways to delay cognitive impairment.

Objective: Hyperlipidemia is closely related to premature acute myocardial infarction (AMI). The present study was performed to explore the correlation between various blood lipid components and the risk of premature AMI. Methods: This is a cross-sectional retrospective study. Consecutive patients with acute ST-segment elevation myocardial infarction (STEMI), who completed coronary angiography from October 1, 2020 to September 30, 2022 in our hospital, were enrolled and divided into premature AMI group (male<55 years old, female<65 years old) and late-onset AMI group. Total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, lipoprotein (a) (Lp (a)), apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA-1), non-HDL-C/HDL-C and ApoB/ApoA-1 were analyzed. The correlation between the above blood lipid indexes and premature AMI was analyzed and compared by logistic regression, restricted cubic spline and receiver operating characteristic curve (ROC). Results: A total of 1 626 patients with STEMI were enrolled in this study, including 409 patients with premature AMI and 1 217 patients with late-onset AMI. Logistic regression analysis showed that the risk of premature AMI increased significantly with the increase of TG, non-HDL-C/HDL-C, non-HDL-C, ApoB/ApoA-1, TC and ApoB quintiles; while LDL-C, ApoA-1 and Lp (a) had no significant correlation with premature AMI. The restricted cubic spline graph showed that except Lp (a), LDL-C, ApoA-1 and ApoB/ApoA-1, other blood lipid indicators were significantly correlated with premature AMI. The ROC curve showed that TG and non-HDL-C/HDL-C had better predictive value for premature AMI. Inconsistency analysis found that the incidence and risk of premature AMI were the highest in patients with high TG and high non-HDL-C/HDL-C. Conclusion: TG, non-HDL-C/HDL-C and other blood lipid indexes are significantly increased in patients with premature AMI, among which TG is the parameter, most closely related to premature AMI, and future studies are needed to explore the impact of controlling TG on incidence of premature AMI.
Humans ; Male ; Female ; Middle Aged ; Aged ; Cross-Sectional Studies ; Cholesterol, LDL ; Retrospective Studies ; ST Elevation Myocardial Infarction ; Apolipoprotein A-I ; Myocardial Infarction ; Cholesterol ; Apolipoproteins B ; Triglycerides ; Cholesterol, HDL ; Lipids ; Lipoproteins

Humans ; Chordoma/surgery* ; Femur ; Biomarkers, Tumor

This paper compared the differences between two kinds of Bufonis Venenum produced by Bufo gargarizans gargarizans and B. gararizans andrewsi, and verified the rationality of the market value orientation of Bufonis Venenum based on the zebrafish mo-del. Twenty batches of Bufonis Venenum from Jiangsu province, Hebei province, Liaoning province, Jilin province, and Liangshan, Sichuan province, including B. gargarizans gargarizans and B. gararizans andrewsi, were collected. The UHPLC-LTQ-Orbitrap-MS combined with principal component analysis was used to compare the differences between two kinds of Bufonis Venenum. According to the limiting conditions of VIP>1, FC<0.5 or FC>2.0, and peak total area ratio>1%, 9 differential markers were determined, which were cinobufagin, cinobufotalin, arenobufagin, resibufogenin, scillaredin A, resibufagin, 3-(N-suberoylargininyl)-arenobufagin, 3-(N-suberoylargininyl)-marinobufagin, and 3-(N-suberoylargininyl)-resibufogenin. The content of 20 batches of Bufonis Venenum was determined according to the Chinese Pharmacopoeia(2020 edition) by high-performance liquid chromatography, and the 2 batches of Bufonis Venenum, CS7(8.99% of total content) and CS9(5.03% of total content), with the largest difference in the total content of the three quality control indexes of the Chinese Pharmacopoeia(bufalin, cinobufagin, and resibufogenin) were selected to evaluate their anti-liver tumor activity based on the zebrafish model. The tumor inhibition rates of the 2 batches were 38.06% and 45.29%, respectively, proving that only using the quality control indexes of the Chinese Pharmacopoeia as the value orientation of Bufonis Venenum market circulation was unreasonable. This research provides data support for the effective utilization of Bufonis Venenum resources and the establishment of a rational quality evaluation system of Bufonis Venenum.
Animals ; Zebrafish ; Bufanolides/analysis* ; Bufonidae ; Chromatography, High Pressure Liquid ; Quality Control ; Cell Line, Tumor