ObjectiveTo investigate the protective effect of resveratrol against blood-brain barrier damage in a rat model of cerebral ischemia-reperfusion and to determine whether this effect is mediated by the C-C motif chemokine ligand 3 (CCL3)/C-C chemokine receptor type 5 (CCR5) signaling pathway　Methods　A total of 100 specific pathogen-free (SPF) male Sprague-Dawley (SD) rats, aged 6-8 weeks, were randomly divided into five groups: sham-operated (Sham), model (MCAO), resveratrol-treated (Res), resveratrol+CCR5 agonist (Res+Agonist), and resveratrol+CCR5 antagonist (Res+Antagonist) groups. The MCAO, Res, Res+Agonist, and Res+Antagonist groups were subjected to middle cerebral artery occlusion (MCAO) for 45 min followed by reperfusion to establish the rat model of cerebral ischemia, while the Sham group underwent carotid artery exposure without ischemia. After reperfusion, resveratrol (60 mg/kg) was intraperitoneally injected in Res, Res+Agonist and Res+Antagonist groups, and an equal volume of normal saline was injected in Sham and MCAO groups. Thirty minutes later, CCR5 agonist (20 μg/kg) was injected via the tail vein in the Res+Agonist group, CCR5 inhibitor (1 mg/kg) was injected via the tail vein in the Res+Antagonist group, and the equal volume of normal saline was injected via the tail vein in the Res, Sham and MCAO groups. Thereafter, resveratrol, CCR5 agonist, CCR5 inhibitor, or saline were administered every 24 hours for 3 consecutive days. After modeling, cerebral infarct volume was evaluated by 2,3,5‑triphenyltetrazolium chloride (TTC) staining. Blood‑brain barrier (BBB) permeability was assessed by Evans blue extravasation. Serum levels of the pro‑inflammatory cytokines interleukin‑1β (IL‑1β), tumor necrosis factor‑α (TNF‑α), and CCL3 were measured by enzyme‑linked immunosorbent assay (ELISA). Histopathological changes in brain tissue were observed by hematoxylin and eosin (HE) staining and Nissl staining. Immunofluorescence staining was used to detect the fluorescence intensity of the microglial marker ionized calcium‑binding adapter molecule 1 (Iba‑1) and CCR5. Western blotting analysis was used to detect proteins associated with the CCL3/CCR5 signaling pathway (CCL3, CCR5) in brain tissue, serum pro-inflammatory cytokines [phosphorylated nuclear factor-kappa B (p-NF-κB)] and blood-brain barrier-related proteins [matrix metalloproteinase 9 (MMP9) and occludin]. ResultsCompared with the Sham group, the MCAO group exhibited significantly increased levels of all injury parameters, including cerebral infarct volume, Evans blue extravasation rate in brain tissue, serum levels of the pro‑inflammatory cytokines (IL-1β, TNF-α, and CCL3), the rate of Iba-1- and CCR5-positive immunofluorescence signals in brain tissue, and the protein expression levels of CCL3, CCR5, p-NF-κB, and MMP9 (all P<0.001), accompanied by markedly decreased expression of occludin (P<0.001). HE and Nissl staining revealed pronounced histopathological damage in the MCAO group.Compared with the MCAO group, the Res group showed significant reductions in all the aforementioned injury indicators and a significant increase in occludin expression (P<0.01), together with ameliorated histopathological changes. Compared with the Res group, the Res+Agonist group displayed significantly elevated injury indicators and decreased occludin expression (P<0.05), with aggravated brain tissue damage. In contrast, the Res+Antagonist group exhibited significant decreases in injury indicators and a significant increase in occludin expression (P<0.05), along with further alleviation of histopathological injury. ConclusionResveratrol attenuates peripheral inflammation in cerebral ischemia‑reperfusion injury by targeting the CCL3/CCR5 signaling pathway, thereby exerting a protective effect on the blood‑brain barrier.

Objective To establish and evaluate an integrated disease-syndrome rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Methods Thirty male Wistar rats were allocated randomly into three groups(n=10 per group):sham operation(sham),2-vessel occlusion(2-VO)group,and sleep deprivation combined with 2-VO(SD+2-VO)group.We comprehensively assessed Qi deficiency and blood stasis syndrome manifestations in the rats using a dual evaluation approach,combining exhaustive swimming tests with quantitative tongue chroma analysis.Cognitive function was evaluated using the Barnes maze,and cerebral blood flow was compared using laser speckle contrast imaging.The histopathology of the hippocampal cytoarchitecture and white matter were examined using hematoxylin-eosin(HE)and Luxol fast blue(LFB)staining,respectively,and ultrastructural alterations of neurons in the hippocampal CA1 region were observed by transmission electron microscopy(TEM).Protein expression levels of NeuN,vascular endothelial growth factor A(VEGFA)and CD31 were detected by Western Blot and immunofluorescence.Results Cerebral blood flow was significantly reduced in rats in the 2-VO group compared with the sham group,but they failed to recapitulate the key clinical hallmarks of Qi deficiency and blood stasis syndrome.In contrast,rats in the SD+2-VO group exhibited significantly reduced locomotor activity,exacerbated cerebral hypoperfusion,shortened swimming duration,and darkened tongue color compared with 2-VO rats.Rats in the SD+2-VO group demonstrated significantly impaired learning and memory abilities in the Barnes maze test.Consistent with these observations,HE staining,TEM,and LFB staining revealed substantial neuronal and white matter damage in the SD+2-VO group.NeuN expression was decreased and VEGFA and CD31 expression levels were increased in the 2-VO and SD+2-VO groups,as shown by Western Blot.Taken together,these findings indicated that the SD+2-VO model effectively recapitulated the clinical features of chronic cerebral ischemia with Qi deficiency and blood stasis pattern.Conclusions The combination of sleep deprivation and bilateral carotid artery occlusion successfully established a rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Compared with the 2-VO model,SD+2-VO model demonstrates more pronounced syndrome manifestations and better clinical relevance,thus providing a valuable animal model for traditional Chinese medicine research on chronic cerebral ischemia.

Objective:To explore the molecular mechanism of miR-4508 regulating the inflammatory response of human bronchial epithelial cells induced by representative chrysotile asbestos.Methods:The chrysotile asbestos was ground into ultrafine dust using a horizontal planetary instrument, and human bronchial epithelium (16HBE) cells were taken as the object of infection. Cell survival rate was detected by cell counting kit-8 method, cytotoxicity was detected by lactate dehydrogenase (LDH) kit. The released of inflammatory factor IL-6 was detected by electrochemical luminescence. The released inflammatory factor IL-8 was detected by enzyme-linked immunosorbent assay. The expression level of miR-4508 was screened and verified by reverse transcription-quantitative real-time polymerase chain reaction. After 16HBE cells were treated with AKT inhibitor MK2206, the phosphorylation levels of AKT and PTEN were detected by western blot. The expression levels of AKT and PTEN and the contents of IL-6 and IL-8 were detected in miR-4508 overexpression and interference experiments.Results:With the increase of chrysotile asbestos exposure concentration, the cell survival rate decreased in a concentration-dependent manner, and the LDH content gradually increased. The secretion of IL-6 and IL-8 in chrysotile 25, 50 and 75 μg/ml groups were (325.92±8.61) pg/ml, (331.51±4.96) pg/ml, (378.74±13.77) pg/ml, and (94.95±3.11) pg/ml, (357.60±1.80) pg/ml, (537.19±3.11) pg/ml, respectively, while the group with 0 μg/ml chrysotile was (95.85±1.20) pg/ml and (7.81±0.00) pg/ml ( P＜0.05). In addition, chrysotile asbestos exposure to 16HBE could induce the high expression of miR-4508 . After pretreatment with MK2206, the phosphorylation levels of AKT and PTEN were decreased, the contents of IL-6 and IL-8 were significantly decreased, and the expression level of miR-4508 was significantly reduced. Overexpression of miR-4508 significantly increased the expressions of AKT and PTEN, and the contents of IL-6 and IL-8 ( P＜0.01). After interfering with miR-4508, the expressions of AKT and PTEN were significantly decreased, and the contents of IL-6 and IL-8 were significantly decreased ( P＜0.01). Conclusions:Chrysotile asbestos can induce the inflammatory response of 16HBE cells and up-regulate the expression level of miR-4508. The up-regulation of miR-4508 promotes the 16HBE inflammatory response induced by chrysotile asbestos through the PI3K/AKT pathway.

Objective To investigate the association of liver radiodensity with the degree and progression of liver fibrosis in patients with chronic hepatitis B(CHB).Methods A retrospective cohort study was conducted among 114 CHB patients who were hospitalized in The First Hospital of Lanzhou University from January to December 2019,and related clinical data were collected,including laboratory tests and abdominal CT.The metabolic characteristics of the patients were assessed,and liver radiodensity was measured.An analysis of variance was used for comparison of normally distributed continuous data between three groups,and the Kruskal-Wallis H rank sum test was used for comparison of continuous data with skewed distribution between three groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between three groups.A logistic regression analysis was used to investigate the influencing factors for the degree of liver fibrosis,and the Cox proportional-hazards regression model analysis was used to investigate the influencing factors for the progression of liver fibrosis in CHB.Results Among the 114 patients enrolled,43(37.72％)had no liver cirrhosis,30(26.32％)were suspected of liver cirrhosis,and 41(35.96％)had liver cirrhosis,with a median follow-up time of 538.5(322.75-1 031.50)days.Liver radiodensity on plain scan(odds ratio[OR]=0.81,95％confidence interval[CI]:0.68-0.97,P=0.025),liver radiodensity on contrast-enhanced scan(OR=0.95,95％CI:0.90-0.99,P=0.037),and liver volume(OR=0.99,95％CI:0.98-0.99,P<0.001)were independent influencing factors for the degree of liver fibrosis.The univariate Cox regression analysis showed that the low level of HDL(hazard ratio=2.81,95％CI:1.04-7.54,P=0.041)was associated with the progression of liver fibrosis in CHB patients,and the degree of liver fibrosis,liver volume,and liver radiodensity showed no significant association with the progression of liver fibrosis(all P>0.05).Conclusion In CHB patients,liver radiodensity is an independent influencing factor for the degree of liver fibrosis,and low HDL has a marked influence on the progression of liver fibrosis.

Objective To explore the impact of gender factors in participant selection during bioequivalence studies,and to provide insights for improving the screening success rate in subsequent trials.Methods A retrospective study was con-ducted to summarize the screening information of healthy subjects in the bioequivalence study conducted in the Phase Ⅰ Clinical Trial Laboratory of the Affiliated Hospital of Xiangnan University from July 2021 to July 2023.The number of failed screening ca-ses in different stages of screening for each project was counted,and the influence of gender factors on subject screening was ana-lyzed.Results A total of 32 bioequivalence studies involving 2 794 subjects,including 1 816 males and 978 females,were in-cluded in the study.The proportion of males was higher in vital signs and BMI abnormalities,and the proportion of females was higher in ECG abnormalities and active withdrawal,and the pass rate was lower in males than in females(40.0％ vs.45.8％),and the existence of the two was statistically significant(P＜0.05).The results of PC A showed that the distribution of data in males was more dispersed,and the distribution of data in females was centralized,and the two could be clearly differentiated.Binary lo-gistic regression analysis showed significant differences between males and females in laboratory test screening failures and BMI(P＜0.05).Further analysis showed that the screening failure rates of blood biochemistry,urine routine,coagulation function and blood transfusion were higher in males than in females,but the screening failure rates of blood routine were lower than those of fe-males.Conclusions Gender is an important influencing factor in the screening process of bioequivalence studies.Including subjects with appropriate gender ratios can help improve enrollment speed and reduce clinical trial costs.

Objective:To observe the therapeutic effect of combining low-frequency pulsed electrical stimulation with Beckman oral muscle exercise training in relieving drooling among persons with Parkinson′s disease (PD).Methods:A random number table was used to divide 120 PD patients with drooling into a mouth muscle training group, an electrical stimulation group, and an observation group, with 40 patients in each group. In addition to routine medication, the oral muscle training group was given Beckman oral muscle exercise training, the electrical stimulation group underwent low-frequency pulsed electrical stimulation treatment, while the observation group was provided with both. Before and after 4 weeks of treatment, the severity of salivation, the frequency of repeated empty swallowing, oral motor function, saliva secretion, and life quality of the three groups were evaluated using the Saliva Rating Scale (DRS), the Repeated Saliva Swallowing Test (RSST), oral motor function grading, the Parkinson′s Disease Saliva Clinical Scale (SCS-PD), saliva weighing, and the PD Quality of Life Scale (PDQ-39).Results:After the treatment the average DRS, SCS-PD, saliva weighing and PDQ-39 results of the observation group were significantly better than those before treatment and better than the other 2 groups′ averages. That group′s average RSST and oral motor function scores had increased significantly compared to before treatment, and compared with the other 2 groups′ averages at the same time point.Conclusions:Combining low-frequency pulsed electrical stimulation with Beckman oral muscle exercise can improve oral motor function, swallowing, and the life quality of PD patients who drool. It is more effective than electrical stimulation or oral muscle exercise training alone. Such combination therapy is worthy of clinical promotion and application.

Objective To investigate the association of liver radiodensity with the degree and progression of liver fibrosis in patients with chronic hepatitis B(CHB).Methods A retrospective cohort study was conducted among 114 CHB patients who were hospitalized in The First Hospital of Lanzhou University from January to December 2019,and related clinical data were collected,including laboratory tests and abdominal CT.The metabolic characteristics of the patients were assessed,and liver radiodensity was measured.An analysis of variance was used for comparison of normally distributed continuous data between three groups,and the Kruskal-Wallis H rank sum test was used for comparison of continuous data with skewed distribution between three groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between three groups.A logistic regression analysis was used to investigate the influencing factors for the degree of liver fibrosis,and the Cox proportional-hazards regression model analysis was used to investigate the influencing factors for the progression of liver fibrosis in CHB.Results Among the 114 patients enrolled,43(37.72％)had no liver cirrhosis,30(26.32％)were suspected of liver cirrhosis,and 41(35.96％)had liver cirrhosis,with a median follow-up time of 538.5(322.75-1 031.50)days.Liver radiodensity on plain scan(odds ratio[OR]=0.81,95％confidence interval[CI]:0.68-0.97,P=0.025),liver radiodensity on contrast-enhanced scan(OR=0.95,95％CI:0.90-0.99,P=0.037),and liver volume(OR=0.99,95％CI:0.98-0.99,P<0.001)were independent influencing factors for the degree of liver fibrosis.The univariate Cox regression analysis showed that the low level of HDL(hazard ratio=2.81,95％CI:1.04-7.54,P=0.041)was associated with the progression of liver fibrosis in CHB patients,and the degree of liver fibrosis,liver volume,and liver radiodensity showed no significant association with the progression of liver fibrosis(all P>0.05).Conclusion In CHB patients,liver radiodensity is an independent influencing factor for the degree of liver fibrosis,and low HDL has a marked influence on the progression of liver fibrosis.

Major depressive disorder in adolescents is a serious psychiatric condition characterized by profound impairment in psychosocial functioning. Its primary symptoms include low mood, irritability, and anhedonia. Although pharmacological treatments and psychotherapy are currently recommended as first-line treatments, their effectiveness is limited, and pharmacological treatments may carry the risk of increased suicidal ideation. Therefore, exploring new, effective, and safe treatment options is an urgent priority. In recent years, intermittent theta burst stimulation (iTBS), a novel form of transcranial magnetic stimulation, has shown promising results in treating treatment-resistant depression in adults, drawing growing interest in its potential use in adolescents. iTBS modulates neural activity through magnetic stimulation of the cerebral cortex and has been shown to alleviate depressive symptoms, particularly when targeting the left dorsolateral prefrontal cortex (DLPFC). Given the high neuroplasticity of the adolescent brain during this critical developmental stage, adolescents may exhibit heightened sensitivity to iTBS, resulting in more enduring neuroregulatory effects. Research highlights the importance of precise targeting and individualized adjustment of stimulation intensity for optimal therapeutic outcomes. Additionally, accelerated iTBS (aiTBS) protocols have demonstrated faster clinical effects in treating acute or severe depression in adolescents, improving treatment adherence and partially mitigating suicidal tendencies. This review summarizes recent progress in the application of iTBS in adolescent depression, with a focus on its mechanisms, treatment parameters, and related research. The goal is to provide theoretical support and practical guidance for the clinical application of iTBS in adolescent depression care.

Objective:To compare and analyze the differences in positioning errors and placement outside the target area between two different image-guided systems(Halcyon and Synergy)in radiotherapy for cervical cancer.Methods:The data of 40 patients with cervical cancer who received treatment in Dezhou People's Hospital from March 2023 to June 2023 were retrospectively selected.Each patient was treated respectively with Halcyon linear accelerator and Synergy linear accelerator,with 20 cases for each treatment method.All patients underwent cone beam computed tomography(CBCT)at kV level to conduct image scanning before radiotherapy,and the obtained CBCT images were matched with the positioned CT images by online.The registration results of left and right(x),head and foot(y)and front and back(z)of three translation direction,and pitch(Rx),rotation(Ry)and deflection(Rz)directions of rotation direction were respectively obtained.The margin of planning target volume(MPTV)was calculated according to positioning expansion formula.The differences of positioning errors and target area expansion between Halcyon and Synergy image-guided systems were compared and analyzed.Results:Halcyon and Synergy image-guided systems obtained respectively 479 and 447 sets of CBCT images.The translational errors of Halcyon image-guided system on x,y,and z directions were respectively(-0.03±0.21),(0.12±0.63)and(0.02±0.15)cm,and the rotational errors of that on Rx,Ry and Rz directions were respectively(0.38±1.26)°,(-0.40±1.02)°,and(0.07±1.07)°.The translational errors of Synergy image-guided system were respectively(-0.07±0.18),(0.08±0.49)and(0.11±0.22)cm on the three directions,and the rotational errors of that were respectively(0.28±1.29)°,(-0.29±1.29)° and(-0.16±1.20)°.The translational error values on the y direction of both image-guided system were larger than that on x and z directions,and the absolute values of the range of translational errors of them were basically within 5 mm.There were no statistically significant difference in the positioning errors of rotation on Rx and Ry directions between Halcyon and Synergy image-guided systems(P＞0.05),while there was a statistically significant difference in the positioning error of rotation on Rz direction between them(t=-3.06,P＜0.05).The MPTV values of Halcyon image-guided system on x,y and z directions were respectively 0.4,1.4 and 0.3 cm,and those of Synergy image-guided system were respectively 0.4,0.9 and 0.5 cm.The expansion boundary of target area of Halcyon image-guided system on the y direction was larger than that of Synergy image-guided system,and that on other directions were all less or equal to 0.5 cm.Conclusion:The MPTV values of Halcyon and Synergy image-guided systems can meet clinical requirements in radiotherapy.The positioning errors and the tube current of the scan of Halcyon image-guided system were larger than those of Synergy image-guided system,but the scanning time and treatment time of that were significantly lower than those of Synergy image-guided system.Different treatment systems can be selected individually for patients according to their different conditions.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.