Objective To study the effects of semiconductor laser irradiation and high voltage static electric fields on small vessel damage in diabetic rats.Methods Fifty healthy male Wistar rats were randomly divided into two groups:8 rats in a normal group and 42 in a diabetic model group.The diabetic models were created by intrape- ritoneal injection of streptozocin.The diabetic model rats were randomly divided into four subgroups:a diabetes group,a semiconductor laser treatment group,a high voltage static electric field treatment group and a comprehensive treatment group receiving combined semiconductor laser and high voltage static electric field exposure.The rats in each treatment group were subjected to the corresponding intervention.After 20 days of treatment,the venous blood, kidney tissue and myocardium tissue of the rats were collected,and the concentrations of blood glucose,insulin,en- dothelin and tissue were detected.Results Compared with the normal group,a significant increase in blood glu- cose and endothelin was observed in the diabetic model group,along with significantly decreased blood insulin and significant small vessel endothelium proliferation in the kidney tissue.Compared with the diabetes group,endothelin levels were significantly lower in all 3 treatment groups,and blood insulin was also higher in the comprehensive treat- ment group.Conclusion There were severe abnormalities in blood glucose,insulin and endothelin as well as mild impairment of small vessel endothelium proliferation in the diabetic rats.Semiconductor laser and high voltage static electric field exposure have a role in treating and preventing these conditions in diabetic rats.

Objective:To investigate the m echanism of D- amino acid oxidase/D- Alanine system in killing K5 6 2 e cells in vitro.Methods:The killing effects of D- Ala on K5 6 2 e cells stably expressing DAAO and GFP were observed.H2 O2 production by DAAO+ cells were m easured by the phenol red oxidation assay.L owry method was used to determ ine the protein quantities of cells and fluorescent intensities of GFP+ cells were assayed by flow cytom eter.Results:KDf Gd cells were killed completely after treated with 2 5 mm ol/L D- Ala for 2 4 h.The effect of D - Ala at 2 0 m mol/L on KDf Gd cells increased apparently within 4 8h,but the same effect was not observed if D - Ala was below 15 m mol/L .The cytotoxicity of D- Ala in KDf Gd cells was more sensitive than in parental K 5 6 2 e cells.The H2 O2 levels in the medium were consistent with the killing effects of D- Ala.Conclusion:The killing effects of DAAO/D- Ala system is m ediated by H2 O2 . [

There are sex differences in some brain areas in mammalians. Parkinson's disease (PD), caused by the mesencephalic substantia nigra (SN) dopaminergic neuronal loss, displays sexual difference, i.e., the incidence is higher and the symptoms are more intense in males than that in females. However, it has not been known whether sexual dimorphisms exist in the SN. Sixty adult Sprague-Dawley rats were randomly divided into 5 groups: (1) Female intact group (F-INT group); (2) Male intact group (M-INT group); (3) Ovariectomized group (OVX group); (4) Castration group (CAST group); (5) Ovariectomized + estrogen-replaced group (OVX-E(2) group): The rats received sequentially physiological dose of estrogen for 3 d from the 7th day after ovariectomization. P50 auditory evoked potential (P50) was recorded for 14 d from electrodes inserted in the rat right SN in quiet and awake state. After recording, the brain tissues were dissected and the tyrosine hydroxylase (TH)-expressing neurons in the compact zone of the SN were counted using immunohistochemical method. The results showed that the number of TH-positive (TH(+)) cells in the SN of normal male animals was less than that in normal female rats (P<0.05), and the T/C ratio of P50 in normal males was significantly less than that in normal females (P<0.01), indicating that there exists sexual difference in function and structure in the SN. No differences in the T/C ratio of P50 or the number of TH(+) cells were found between M-INT and CAST groups. The T/C ratio of P50 and the number of TH(+) cells in the SN in OVX group were reduced significantly compared with those in F-INT group (P<0.01). There was no significant difference in the T/C ratio of P50 and the number of TH(+) cells in the SN between OVX- E(2) and F-INT groups 15-20 d after estrogen replacement, suggesting that estrogen can promote the survival and functional recovery of dopaminergic neurons in the SN. The results suggest that there exist sex-specific differences in the dopaminergic neurons in the SN structurally and functionally. The difference of estrogen level in cerebra between male and female animals may account for the sexual differences. Endogenous estrogen plays an important role in maintaining the integrity and modulating the functional activity of dopamine system in the SN.
Animals ; Dopaminergic Neurons ; cytology ; Estrogens ; pharmacology ; Evoked Potentials, Auditory ; Female ; Male ; Orchiectomy ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Sex Characteristics ; Substantia Nigra ; cytology

Objective To determine whether the combination of traditional risk factors and quantitative coronary angiography (QCA) assessment could provide accurate prognostic information on a population-based study including 1137 adults with subclinical artherosclerosis and with coronary risk factors. Methods Participants underwent coronary angiography examination before the minimal stenotic diameters, segment diameters, percent stenosis, plaque areas. Other parameters were analyzed by the computer-assisted Coronary Angiography Analysis System. The Framingham Risk Score for each participant was assessed. During the 1 year follow-up period, all kinds of endpoint cardiovascular events were screened. Endpoint events were defined as death from coronary heart disease, nonfatal myocardial infarction (MI) or unstable angina pectoris. Results During the 1 year of follow-up period, a total of 124 participants developed an endpoint event, which was significantly associated with the Framingham Risk Score, calcium of plaques and the plaque areas (all Ps＜0.05).The QCA score incorporated with the QCA parameters was related to the endpoint events. The Framingham Risk Score was combined with QCA score through logistic regression for prediction of end-point events. Data from the ROC analysis showed the accuracy of this prediction algorithm was superior to the accuracy when variables themselves were used. The event-free survival rate was inferior to the control group in participates under high risk, when being screened with this prediction algorithm (P＜0.05). Conclusion The risk of cardiovascular attack in subclinical artherosclerosis individual seemed to be associated with the Framingham Risk Score, calcium of plaques and the plaque areas. When the traditional risk factors (the Framingham Risk Score) were combined with QCA, the new method could provide more prognostic information on those adults with subclinical artherosclerosis.

OBJECTIVE: To study whether tricalcium phosphate(TCP) wear particles cause injuries of periprosthetic osteocytes in the mouse calvaria, and to explain its molecular mechanism. METHODS: Thirty six-week(ICR)male mice were randomly divided into sham group, model (TCP) group and 3-methyladenine (3-MA) group. A murine calvarial model of osteolysis was established by 30 mg of TCP wear particles implantation over the periosteum around the middle suture of calvaria in mice. On the second postoperative day, the autophagy specific inhibitor 3-MA (1.0 mg/kg) was subcutaneously injected to the calvaria in the 3-MA-treated mice every other day. After 2 weeks, blood and the calvaria were obtained. Micro-CT was used to detect bone mineral density(BMD), bone volume fraction (BVF) and porosity number. HE staining and flow cytometry were performed to analyze the viability and apoptosis of periprosthetic osteocytes. The serum levels of dentin matrix protein 1(DMP-1) and sclerostin (SOST) were determined by ELISA. The proteins expressions of DMP-1, SOST, Beclin-1 and microtuble-associated protein 1 light chain 3 (LC-3) were detected by Western blot in the calvaria osteocytes. RESULTS: Compared with the sham group, the mice in the TCP group showed that a significant decrease in the viability of periprosthetic osteocytes, but obvious increases in number of osteocytes death and osteocytes apoptosis (<0.05), and in serum level and protein expression of SOST; significant decreases in serum level and protein expression of DMP-1 (<0.05), and remarkable up-regulation of autophagy-related factors beclin-1 and the conversion of LC3-Ⅱ from LC3-I in the calvaria osteocytes. Compared with TCP group, the mice in the 3-MA group showed that injuries of calvaria osteocytes were obviously aggravated, and osteocytes apoptosis was significantly increased (<0.05). CONCLUSIONS TCP wear particles can cause injuries of periprosthetic osteocytes via activation of apoptosis and autophagy, which promotes osteolysis around the prosthesis osteolysis and joint aseptic loosening.
Animals ; Apoptosis ; Beclin-1 ; metabolism ; Bone Density ; Calcium Phosphates ; adverse effects ; Extracellular Matrix Proteins ; metabolism ; Glycoproteins ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Microtubule-Associated Proteins ; metabolism ; Osteocytes ; pathology ; Osteolysis ; Prostheses and Implants ; adverse effects ; Skull

Objective To study the mechanisms of vertebrae semi-dislocation of Tuina manipulation for treating patients with lumbar intervertebral disc protrusion (LIDP) by observing the three-dimensional (3D) displacement of lumbar before and after Tuina manipulation. Methods Ten LIDP patients were selected and evenly divided into two groups: Group 1 as tendon-smoothing manipulation group (relaxing group), Group 2 as tendon-smoothing plus adjusting manipulation group (adjusting group). Besides, Group 3 as control group was established by 5 healthy volunteers treated with tendon-smoothing manipulation. Before and after manipulation intervention, all subjects were scanned from L1 to L5 segment by using Philips 64 spiral CT under equal conditions for accessing the volume data. ITK reconstruction software was used to reconstruct each lumbar skeleton for finite element analysis. The 3D displacements and angular displacements among three groups were compared. Results 3D displacement from L1 to L5 segment all changed in three groups. For adjusting group, the angular displacements at X-axis in L3 segment was (1.77±0.46)°, and that in L4 segment at X-axis and Y-axis was (1.78±0.53)° and (1.89±0.75)°, respectively, which was significantly larger than relaxing group and control group (P<0.05); the angular displacements at X-axis from L1 to L5 segment were (1.50±0.47)°, (1.55±0.57)°, (1.77±0.46)°, (1.78±0.53)°, (1.61±0.39)°, respectively, which were significantly larger than control group (P<0.05); displacement at Y-axis in L3 segment was (2.87±0.74) mm, and that at X-axis in L4 segment was (1.68±0.64) mm, which were significantly larger than relaxing group and control group (P<0.05); displacement at X-axis in L1, L4 and L5 segment was (1.28±0.21),（1.68±0.64）, (1.30±0.51） mm, and that at Y-axis in L1 to L3 segment was (1.92±0.42), (2.25±0.61), (2.87±0.74) mm, which was significantly larger than control group (P<0.05). The angular displacements and displacements of L1 to L5 segment in relaxing group were larger than those in control group, but without any significant differences. Conclusions Compared with relaxing manipulation, adjusting manipulation played a more obvious adjusting role in instability and degenerative lumbar vertebra, especially for angular displacements in X-axis, and displacements in X-axis and Y-axis. Namely, the mechanisms of vertebrae semi-dislocation of adjusting manipulation were to make horizontal and rotational displacements at lumbar vertebra other than upper and lower displacement. The effect of relaxing manipulation was not so obvious on lumbar structure of LIDP patients.

BACKGROUND: The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses. METHODS: We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed. RESULTS: All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline. CONCLUSIONS Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.
Humans ; Lung Neoplasms/metabolism* ; Interleukin-5/therapeutic use* ; Tumor Necrosis Factor-alpha/therapeutic use* ; Retrospective Studies ; Programmed Cell Death 1 Receptor ; Biomarkers ; Immunotherapy ; Disease Progression ; B7-H1 Antigen