AIM: To investigate and clarify the intervention mechanism of trigonelline(TRG)in preventing ferroptosis in ARPE-19 cells based on the Nrf2/HO-1/GPX4 pathway.METHODS: The ARPE-19 cells were cultured and subsequently treated with varying concentrations of trigonelline to ascertain the most effective concentration for modulating the cells. Then the cells were categorized into distinct groups, including normal control(NC)group, high glucose(HG)group, Fer-1 group, TRG group based on the determined concentration. Samples from each group were then gathered to assess relevant indicators. The intracellular levels of glutathione(GSH), malondialdehyde(MDA), and Ferrion were quantified in accordance with the protocols provided by the GSH, MDA, and Ferrion detection kits. Flow cytometry was employed to measure the ROS levels within each group. Additionally, Western blot analysis was conducted to examine the expression of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase-1(HO-1), glutathione peroxidase(GPX4), and acyl-CoA synthetase long-chain family member 4(ACSL4)across the different groups.RESULTS: The preconditioning intervention with 40 μg/mL TRG effectively mitigated the decline in cell activity induced by high glucose levels. The levels of reactive oxygen species(ROS)and MDA in the HG group were markedly elevated compared to the NC group; and the TRG group exhibited significantly reduced levels of ROS and MDA compared to those of the HG group, with the antioxidant stress index GSH showing opposite trends to those of ROS and MDA across all the groups. Whereas the Fer-1 and TRG groups showed decreased expression levels of ACSL4 protein and iron ions, and the expression levels of Nrf2, HO-1 and GPX4 in the Fer-1 and TRG groups were increased.CONCLUSION: TRG protects ARPE-19 cells from the detrimental effects of high glucose by targeting the Nrf2/HO-1/GPX4 signaling pathway to counter ferroptosis.

Objective:To investigate the interaction of platelet factor 4(PF4)with tumor necrosis factor-α(TNF-α)in the pathoge-nesis of chronic periodontitis(Ⅲ-C).Methods:22 patients with chronic periodontitis(Ⅲ-C)and 22 subjects with periodontal health were recruited.Before and after periodontal treatment,the concentration of PF4 and TNF-α in gingival crevicular fluid(GCF)and ser-um,the amount of PF4 released by platelets after lipopolysaccharide(LPS)stimulated peripheral blood platelets were measured by ELISA.Flow cytometry was used to calculate the number of platelets in GCF before and after treatment.Results:The concentrations of PF4 and TNF-α in the GCF and serum of the patients were higher than those in the periodontal healthy group(P＜0.05).After treat-ment,the concentrations of PF4 and TNF-α in the GCF were significantly lower than those before treatment(P＜0.05),and the con-centrations of PF4 and TNF-α in the serum were unchanged(P＞0.05).After LPS stimulation of the platelets in blood before and after treatment,the concentration of PF4 released by the platelets was much higher in the patients than that in the healthy controls(P＜0.01),and the concentration was significantly lower after periodontal treatment than before treatment(P＜0.01).The number of CD41/CD61 double positive platelets and CD45 negative cells in GCF before periodontal treatment were 85 times and 87 times higher than those in periodontal healthy subjects,respectively(P＜0.01).Conclusion:PF4 and TNF-α have synergistic effect in the patho-genesis of chronic periodontitis.

Objective To observe the effect of Baduanjin exercise on depression,sleep quality and life quality of patients with breast cancer in the rehabilitation period.Methods A total of 76 breast can-cer patients in postoperative rehabilitation were randomly divided into an intervention group of 38 with 2 dropping out,and a control group of 38 with 3 dropouts.Both groups received routine nursing and rehabilitation after breast cancer surgery,while the intervention group additionally practised Baduanjin for 6 weeks.The Beck Depression Inventory-Ⅱ(BDI-Ⅱ-C),Pittsburgh Sleep Quality Index(PSQI)and Quality of Life Questionnaire Core 30(EORTC QLQ-C30)were used to evaluate both groups be-fore,as well as 3 and 6 weeks after intervention.Results After 3-week intervention,the average BDI-Ⅱ-C score,the total PSQI score and the scores of all dimensions except for the hypnotic drug dimen-sion of the intervention group was significantly lower than before treatment(P<0.05),and the control group at the same time point(P<0.05),while the scores of physical,emotional,cognitive,social and role function in EORTC QLQ-C30 were significantly higher than the latter(P<0.05).Three weeks lat-er,the average BDI-Ⅱ-C score,the total PSQI score and the scores of all dimensions except for the hypnotic drug dimension of the intervention group was significantly lower than before treatment(P<0.05),and the control group at the same time point(P<0.05),while the various scores of EORTC QLQ-C30 were significantly higher than the latter(P<0.05).Compared with after 3-week intervention,after 6-week intervention,the average BDI-Ⅱ-C score,the total PSQI score and the scores of its all dimensions except for the sleep disorder dimension of the intervention group decreased significantly,while all dimension scores of EORTC QLQ-C30 except the cognitive function dimension increased sig-nificantly(P<0.05 for all).Conclusion Baduanjin is feasible in improving the sleep and life quality of patients in the rehabilitation period after breast cancer surgery,and relieving their depression.

Cellular immune responses as well as generalized and periarticular bone loss are the key pathogenic features of rheumatoid arthritis (RA). Under the pathological conditions of RA, dysregulated inflammation and immune processes tightly interact with skeletal system, resulting in pathological bone damage via inhibition of bone formation or induction of bone resorption. Single-cell omics technologies are revolutionary tools in the field of modern biological research.They enable the display of the state and function of cells in various environments from a single-cell resolution, thus making it conducive to identify the dysregulated molecular mechanisms of bone destruction in RA as well as the discovery of potential therapeutic targets and biomarkers. Here, we summarize the latest findings of single-cell omics technologies in osteoimmunology research in RA. These results suggest that single-cell omics have made significant contributions to transcriptomics and dynamics of specific cells involved in bone remodeling, providing a new direction for our understanding of cellular heterogeneity in the study of osteoimmunology in RA.
Humans ; Osteoclasts/physiology* ; Arthritis, Rheumatoid/pathology* ; Inflammation/pathology* ; Bone and Bones/pathology* ; Bone Resorption/pathology*

Objective:To investigate the incidence of various non-motor symptoms (NMS) in early stage of Parkinson′s disease (PD) patients and the differences between the body-first and brain-first subtypes.Methods:A total of 121 patients with PD (Hoehn-Yahr stage 1-2) were recruited from PD Clinic, Department of Neurology, Beijing Hospital from January 2012 to January 2015. The general information and clinical features of the patients were collected. The minimal diagnostic criteria of parasomnias described in the International Classification of Sleep Disorders-Revised were used to diagnose rapid eye movement sleep behavior disorder (RBD).According to the sequence of RBD and motor symptoms, the patients were divided into 2 groups: body-first subtype and brain-first subtype. NMS was evaluated by the Non-Motor Symptom Questionnaire (NMSQuest). The clinical features and the incidence of various NMS were compared between the 2 groups. The Unified Parkinson′s Disease Rating Scale (UPDRS) was used to evaluate the severity of the disease, and its third part (UPDRS-Ⅲ) was used to evaluate the motor function of the patients. Hamilton Rating Scale for Depression (HAMD) and Hamilton Rating Scale for Anxiety (HAMA) were used to evaluate the depression and anxiety status of the patients. The sleep status of patients was assessed by Parkinson′s Disease Sleep Scale (PDSS). The quality of life of the patients was assessed by 39-item Parkinson′s Disease Questionnaire (PDQ-39).Results:Of all the patients, 49.59% (60/121) had the body-first subtype and 50.41% (61/121) had the brain-first subtype of PD. There was no significant difference in UPDRS-Ⅲ score between the 2 groups. The average number of NMS in all PD patients was 10.97±4.88. Body-first subtype patients had higher NMS incidence than brain-first subtype in difficulty in swallowing [46.7% (28/60) vs 23.0% (14/61), χ 2=7.507, P=0.006], nausea and vomiting [16.7% (10/60) vs 3.3% (2/61), χ 2=6.069, P=0.014], constipation [85.0% (51/60) vs 55.7% (34/61), χ 2=12.393, P<0.001], fecal incontinence [8.3% (5/60) vs 0 (0/61), χ 2=5.302, P=0.021], difficulty in remembering recent events [58.3% (35/60) vs 32.8% (20/61), χ 2=7.962, P=0.005], loss of interest [43.3% (26/60) vs 24.6% (15/61), χ 2=4.743, P=0.029], inattention [45.0% (27/60) vs 19.7% (12/61), χ 2=8.884, P=0.003], depression [55.0% (33/60) vs 34.4% (21/61), χ 2=5.181, P=0.023], intense vivid dreams [73.3% (44/60) vs 39.3% (24/61), χ 2=14.196, P<0.001] and restless legs [53.3% (32/60) vs 27.9% (17/61), χ 2=8.140, P=0.004]. The differences were significant. Body-first subtype and NMSQuest ( r=-0.489, P<0.001), UPDRS ( r=-0.189, P=0.038), HAMD ( r=-0.231, P=0.011), HAMA ( r=-0.298, P=0.001) and PDQ-39 scores ( r=-0.276, P=0.002) were negatively correlated. Body-first subtype and PDSS score was positively correlated. NMSQuest (Δ R2=0.265, P<0.001) was the main determinant of PDQ-39 score. Conclusions:PD patients are accompanied by various NMS, which is a major factor affecting the quality of life. Compared with brain-first subtype, body-first subtype might have more NMS burden and higher incidence rate in most NMS in early PD patients.

Transcription, Genetic

A middle-aged man was presented with poor appetite, polyuria, polydrpsia, and headache. A sellar mass was found, along with total pituitary hypofunction and visual field defect. A biopsy of the lesion via the trans-sphenoidal approach showed inflammatory changes and granuloma formation. However, repeated cerebrospinal fluid and pathogenic examination of the pathological tissue showed no positive indications. The initial diagnosis considered autoimmune hypophysitis, and treatment of glucocorticoids combined with immunosuppressants was administered, which led to a temporary shrinkage of the lesion, but it gradually enlarged subsequently. After multidisciplinary discussion, a high possibility of pituitary tuberculosis infection was decided upon. After standardized anti-tuberculosis treatment was initiated, the lesion reduced noticeably and the patient′s condition improved. Pituitary tuberculosis infection is incredibly rare and extremely easy to misdiagnose. This case was diagnosed and treated in a timely and effective manner through a multidisciplinary approach, highlighting the importance of such an approach in dealing with rare diseases.

Radiopharmaceutical dynamic imaging typically necessitates intravenous injection via the bolus method. However, manual bolus injection carries the risk of handling errors as well as radiological injuries. Hence, there is potential for automated injection devices to replace manual injection methods. In this study, the effect of micro-bolus pulse injection technology was compared and verified by radioactive experiments using a programmable injection pump, and the overall bubble recognition experiment and rat tail vein simulation injection verification were performed using the piezoelectric sensor preloading method. The results showed that at the same injection peak speed, the effective flushing volume of micro-bolus pulse flushing (about 83 μL/pulse) was 49.65% lower than that of uniform injection and 25.77% lower than that of manual flushing. In order to avoid the dilution effect of long pipe on the volume of liquid, the use of piezoelectric sensor for sealing preloading detection could accurately predict the bubbles of more than 100 μL in the syringe. In the simulated injection experiment of rat tail vein, when the needle was placed in different tissues by preloading 100 μL normal saline, the piezoelectric sensor fed back a large difference in pressure attenuation rate within one second, which was 2.78% in muscle, 17.28% in subcutaneous and 54.71% in vein. Micro-bolus pulse injection method and piezoelectric sensor sealing preloading method have application potential in improving the safety of radiopharmaceutical automatic bolus injection.
Animals ; Rats ; Radiopharmaceuticals/administration & dosage*

Objective To investigate the application value of tenofovir alafenamide fumarate (TAF) in elderly patients with chronic hepatitis B (CHB) and its influence on bones and kidneys. Methods A total of 36 CHB patients, aged ≥60 years, who received TAF antiviral therapy in Qingdao Municipal Hospital, The Affiliated Hospital of Qingdao University, Qingdao Sixth People's Hospital, Chengyang People's Hospital, and Jimo People's Hospital from June 2021 to October 2022 were enrolled in this study, and all patients received TAF (25 mg/d) antiviral therapy. Related data were collected at baseline and weeks 24 and 48 of treatment, including virological indicators, biochemical parameters, urinary protein electrophoresis indices, transient elastography (FibroScan), and bone mineral density. Virological indicators included high-sensitivity HBV DNA quantification; biochemical parameters included total bilirubin, direct bilirubin (DBil), indirect bilirubin (IBil), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, total bile acid (TBA), glucose, blood urea nitrogen, creatinine, estimated glomerular filtration rate, and cystatin C (Cys C); urinary protein electrophoresis indices included urinary β2 microglobulin (β2-MG), urinary retinol (URBP), and urinary α1 microspherin (α1-MG). The paired t -test was used for comparison of normally distributed continuous data before and after treatment, and the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment; the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 36 CHB patients completed 24 weeks of follow-up. The complete virological response rate after 24 weeks of treatment was higher than that at baseline [83.3% (30/36) vs 77.8% (28/36), χ 2 =0.36, P =0.55], and there were significant reductions in DBil ( t =-2.42, P =0.02) and Cys C ( t =-4.34, P < 0.001) from baseline to week 24. A total of 18 CHB patients completed 48 weeks of follow-up. The complete virological response rate after 48 weeks of treatment was higher than that at baseline (94.4% vs 77.8%, χ 2 =2.22, P =0.34), and there were significant increases in IBil ( t =2.43, P =0.03), TBA ( Z =-2.24, P =0.03), and bone mineral density T score of lumbar vertebra ( t =2.92, P = 0.01) and femoral neck ( t =2.42, P =0.03) and a significant reduction in liver stiffness measurement ( t =-2.31, P =0.03). There were no significant changes in β2-MG, URBP, and α1-MG after treatment (all P > 0.05). Conclusion TAF has a good antiviral effect in CHB patients aged ≥60 years and can help more CHB patients achieve complete virological response, without causing damage to the kidney, and it can also improve bone mineral density and liver fibrosis degree.

In clinical practice, radiopharmaceutical dynamic imaging technology requires the bolus injection method to complete injection. Due to the failure rate and radiation damage of manual injection, even experienced technicians still bear a lot of psychological burden. This study combined the advantages and disadvantages of various manual injection modes to develop the radiopharmaceutical bolus injector, and explored the application of automatic injection in the field of bolus injection from four aspects: radiation protection, occlusion response, sterility of injection process and effect of bolus injection. Compared with the current mainstream manual injection method, the bolus manufactured by the radiopharmaceutical bolus injector based on the automatic hemostasis method had a narrower full width at half maximum and better repeatability. At the same time, radiopharmaceutical bolus injector had reduced the radiation dose of the technician's palm by 98.8%, and ensured more efficient vein occlusion recognition performance and sterility of the entire injection process. The radiopharmaceutical bolus injector based on automatic hemostasis has application potential in improving the effect and repeatability of bolus injection.
Radiopharmaceuticals ; Injections ; Hand