BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

Postmenopausal osteoporosis (PMOP) is a chronic metabolic bone disease caused by a decrease in estrogen levels. With the acceleration of population aging process, the public health burden caused by it is becoming increasingly severe. The prevalence rate of osteoporosis in people over 65 years old in China is as high as 32%, which is especially prominent after menopause, which is about 5 times that of elderly men. About 40% of postmenopausal women are at risk of osteoporotic fractures, with a disability rate of up to 50% and a fatality rate of about 20%. The prevention and treatment of osteoporosis has become a major public health issue of global concern, and it is particularly urgent to develop reasonable and effective prevention and treatment programs and explore their scientific basis. Exercise is an important non-drug means for the prevention and treatment of PMOP, it can improve estrogen levels and the expression of bone formation transcription factors, and inhibit the levels of proinflammatory factors and bone resorption markers, macroscopically manifested by the improvement of bone microstructure and bone density. However, the effectiveness of exercise in improving bone mineral density (BMD) remains controversial. Some studies revealed significant changes of bone to mechanical stimulation, while others showed no significant effect of mechanical training, this heterogeneity in bone adapt to mechanical stimulation is particularly evident in postmenopausal women. Although the evidence that a wide range of exercise programs can improve osteoporosis, the optimal solution to address bone mineral loss remains unclear. The most effective exercise type, dosage and personalized adaptation are still being determined. This study will fully consider the differences in gender and hormone levels, searching and screening randomized controlled trials of PubMed, CNKI and other databases regarding exercise improving bone mineral density in women with PMOP. Strictly following the PRISMA guidelines to reviewed and compared the effects of different types of exercise modalities on BMD at different sites in women with PMOP by network Meta-analysis, to provide theoretical guidance to maintain or improve BMD in women with PMOP.

Psoriasis is a chronic inflammatory skin disease with a polygenic genetic background. Its etiology remains unclear， and its pathogenesis is complex and refractory， collectively posing significant challenges in its treatment and greatly affecting the physical and mental health of patients. With the advantages of multi-target and multi-pathway treatment， traditional Chinese medicine has shown unique efficacy and value in the diagnosis and treatment of psoriasis. Modern doctors have a lot of discussion on psoriasis， and most of them tend to treat the disease by solving disorders of the blood system. They think that the disease is closely related to the "heat in the blood". Combining the clinical characteristics and accompanying symptoms of psoriasis， this article traced the causes of "heat in the blood" in psoriasis and believed that multiple internal and external factors have prevented the smooth circulation of Qi. Yang Qi Fuyu （stagnation） and transformation into heat and toxicity is the source of "heat in the blood" in psoriasis. Furthermore， it was proposed that "Fuyu" is the core pathogenesis of psoriasis. The etiology of "Fuyu" is complex， such as external wind and cold pathogens， emotional injuries， internal accumulation of dampness， and deficiency of healthy Qi， all of which can disrupt the ascending and descending movement of Qi， impede the circulation of Qi and fluids， close the pores and skin texture， and subsequently lead to stagnation. Based on the above understanding， "resolving stagnation" is crucial for treating the disease. Many doctors have explored the treatment ideas of psoriasis from the perspectives of dispelling wind， warming cold， regulating Qi， eliminating dampness， tonifying deficiency， and external treatment， aiming to remove the causes， promote the circulation of Qi and fluids， and resolve stagnation and heat. Clinical studies have shown that the therapies can relieve clinical symptoms， reduce recurrence rate， and improve quality of life， which also have good safety in the treatment of psoriasis. This article discussed the treatment of psoriasis from the perspective of "Fuyu"， enriching the understanding of TCM regarding the etiology and pathogenesis of psoriasis. It is aiming to serve as an effective supplement to the "treating by solving disorders of the blood system" approach and provide a reference for clinical diagnosis and treatment of psoriasis.

Psoriasis is a chronic inflammatory skin disease with a polygenic genetic background. Its etiology remains unclear， and its pathogenesis is complex and refractory， collectively posing significant challenges in its treatment and greatly affecting the physical and mental health of patients. With the advantages of multi-target and multi-pathway treatment， traditional Chinese medicine has shown unique efficacy and value in the diagnosis and treatment of psoriasis. Modern doctors have a lot of discussion on psoriasis， and most of them tend to treat the disease by solving disorders of the blood system. They think that the disease is closely related to the "heat in the blood". Combining the clinical characteristics and accompanying symptoms of psoriasis， this article traced the causes of "heat in the blood" in psoriasis and believed that multiple internal and external factors have prevented the smooth circulation of Qi. Yang Qi Fuyu （stagnation） and transformation into heat and toxicity is the source of "heat in the blood" in psoriasis. Furthermore， it was proposed that "Fuyu" is the core pathogenesis of psoriasis. The etiology of "Fuyu" is complex， such as external wind and cold pathogens， emotional injuries， internal accumulation of dampness， and deficiency of healthy Qi， all of which can disrupt the ascending and descending movement of Qi， impede the circulation of Qi and fluids， close the pores and skin texture， and subsequently lead to stagnation. Based on the above understanding， "resolving stagnation" is crucial for treating the disease. Many doctors have explored the treatment ideas of psoriasis from the perspectives of dispelling wind， warming cold， regulating Qi， eliminating dampness， tonifying deficiency， and external treatment， aiming to remove the causes， promote the circulation of Qi and fluids， and resolve stagnation and heat. Clinical studies have shown that the therapies can relieve clinical symptoms， reduce recurrence rate， and improve quality of life， which also have good safety in the treatment of psoriasis. This article discussed the treatment of psoriasis from the perspective of "Fuyu"， enriching the understanding of TCM regarding the etiology and pathogenesis of psoriasis. It is aiming to serve as an effective supplement to the "treating by solving disorders of the blood system" approach and provide a reference for clinical diagnosis and treatment of psoriasis.

AIM To investigate the protective effects of Shuangyi Qushi Tongluo Capsules(Shuangyi Capsules)on Dexamethasone(Dex)induced osteoporosis in mice.METHODS The C57BL/6J mice were randomly divided into the control group,the model group,the Xianling Gubao Capsules group(1.5 g/kg),and the low-dose,moderate-dose,and high-dose Shuangyi Capsules groups(0.6,1.2,and 2.4 g/kg).The mouse model of osteoporosis was induced by 8-week intraperitoneal injection of Dex sodium phosphate injection(5 mg/kg).The mice had their femur osteogenesis observed with hematoxylin and eosin(HE)staining and tartrate-resistant acid phosphatase(TRAP)staining;their serum alkaline phosphatase(ALP)and osteocalcin(BGP)activities detected by ELISA;their femoral mRNA expressions of Col-Ⅰ,OCN,and OPN detected by RT-qPCR;and their femoral protein expressions of OPG and RANKL detected by Western blot.Upon the MC3T3-E1 cells exposed to Dex and Shuangyi Capsules,their viability was evaluated by CCK-8 assay;their mineralization determined by alkaline phosphatase staining and alizarin red staining(ARS);and their intracellular ROS level detected using DCFH-DA probe.RESULTS Compared with the model group,Shuangyi Capsules groups demonstrated improved fracture of femoral trabeculae and reduced number of osteoclasts;increased serum ALP and BGP activities(P＜0.05,P＜0.01);increased femoral expressions of Col-Ⅰ mRNA and OPG protein(P＜0.05,P＜0.01);and decreased RANKL protein expression(P＜0.05).Compared with the MC3T3-E1 cells stimulated by Dex,those underwent further treatment of Shuangyi Capsules demonstrated increased cell viability and ALP activity(P＜0.05,P＜0.01);increased mineralization and calcium nodule formation;increased expressions of Col-Ⅰ,OCN,OPN mRNA and OPG protein(P＜0.05,P＜0.01);decreased RANKL protein expression(P＜0.05,P＜0.01);and reduced ROS levels.CONCLUSION Shuangyi Capsules ameliorate Dex-induced osteoporosis in mice by suppressing osteoclast overactivation,enhancing osteoblast activity,and stimulating bone formation through modulation of Col-Ⅰ,OCN,OPN mRNA and OPG/RANKL protein levels.

Objective:To analyze the learning curve of TiRobot-assisted lumbar pedicle screw fixation (LPSF) by cumulative sum (CUSUM) test method.Methods:The clinical data of 50 patients who underwent TiRobot-assisted LPSF from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. CUSUM analysis and learning curve fitting were performed with robot usage time as the main indicator with the time for each step refined (robot registration time, path planning time and guide wire placement time), to select the best learning curve fitting model with the R2 value closest to 1. Using the turning point of the learning curve as the boundary, the learning curve was divided into two stages as learning stage and maturity stage, and then the observation indexes were compared between the two stages. Results:All 50 patients successfully completed the surgery without perioperative complications, with a total of 244 pedicle screws implanted. The total robot usage time and robot registration time showed a gradually decreasing trend with the increase of case number, and the learning curves were successfully fitted and reached their peaks at the seventeenth and thirteenth cases respectively. The entire learning process was divided into learning stage (17 cases) and maturity stage (33 cases) based on the turning point of the learning curve of total robot usage time. The path planning time and guide wire placement time did not show significant changes with the increase in the case number. The total robot usage time, robot registration time and the intraoperative blood loss in the learning stage were significantly higher than those in the maturity stage: (35.35 ± 1.58) min vs. (30.61 ± 0.43) min, (20.83 ± 1.56) min vs. (14.94 ± 0.29) min and 400 (150, 500) ml vs. 200 (110, 300) ml, the guide wire placement time of per screw was significantly lower than that in the maturity stage: 2.00 (1.83, 2.34) min/screw vs. 2.33 (2.13, 2.69) min/screw, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the path planning time, path planning time of per screw, guide wire placement time and the accuracy of screw placement between two stages ( P>0.05). Conclusions:TiRobot-assisted LPSF is a new technology with safety and effectiveness, and it has a relatively short learning curve. To achieve technological maturity, at least 17 surgeries are required with accumulated experience, and the robot registration is the main step of the learning process. After reaching maturity stage, the robot usage time is significantly shortened and intraoperative trauma is significantly reduced while the relatively high screw placement accuracy is ensured.

Human immunodeficiency virus（HIV）entry inhibitors are important in preventing HIV infection by specifically targeting viral envelope proteins（gp120/gp41）or host receptors（CD4/CCR5/CXCR4）to inhibit HIV entry into host cells. This article systematically reviews the research progress of HIV entry inhibitors in recent years，and some of the novel inhibitors such as Fostemsavir，Ibalizumab，and bifunctional fusion inhibitors（2P23-iMab）have shown better effects in inhibiting multidrug-resistant strains. Although great progress has been made in the research and development of HIV entry inhibitors，there are still a series of challenges including drug resistance，drug limitation，target toxicity，which limit their widespread clinical application. Future research directions should focus on multi-target combination strategies，broad-spectrum neutralizing antibody development，and long-term design. In summary，the analyses on the research progress，challenges and future development directions of HIV entry inhibitors will provide a reference for the further research and development and optimization of HIV entry inhibitors，and then promote the development of AIDS prevention and control.

Exosome play a crucial role in human immunodeficiency virus（HIV）infection. They share high similarities with HIV virions in physicochemical properties and secretion mechanisms：both the formation and secretion of exosome and the budding of HIV depend on the endosomal sorting complex required for transport（ESCRT）complex and VPS4 protein，with their membrane structures being phospholipid bilayers and comparable ranges of diameter and density. These similarities pose challenges to related research. Exosome participate in HIV infection through multiple mechanisms，including promoting HIV entry，inhibiting HIV replication，activating HIV latent reservoirs，and engaging in host antiviral immune responses. In terms of clinical applications，the potential of exosome as biomarkers or vaccine carriers has attracted attention，showing translational prospects. In summary，exosome influence the progression of HIV infection through complex mechanisms，and their application prospects in diagnostic markers，vaccine development，and therapeutic targets merit in-depth exploration.

BACKGROUND:Studies have shown that vascular factors have an important impact on the occurrence of diabetic foot.OBJECTIVE:To investigate the important role of angiopoietin-like protein 4 in the formation of diabetic foot.METHODS:(1)Bioinformatics analysis was performed on the gene expression profile data of diabetic foot patients to find the key genes.The skin samples of diabetic foot patients and healthy people were collected for hematoxylin-eosin staining,immunohistochemical staining,and qRT-PCR experiments to detect the expression of angiopoietin-like protein 4.(2)The immortalized human skin fibroblast cell line and primary human umbilical vein endothelial cells were cultured.The two kinds of cells were divided into control group and exogenous angiopoietin-like protein 4 supplemented group.The migration ability and proliferation ability of fibroblasts were detected by scratch assay and CCK-8 assay.The proliferation ability of endothelial cells was detected by Ki67 assay.RESULTS AND CONCLUSION:(1)Bioinformatics analysis results showed that the down-regulation of angiopoietin-like protein 4 gene might be the key gene leading to the formation of diabetic foot.(2)Hematoxylin-eosin staining exhibited that compared with normal skin,angiopoietin-like protein 4 was weakly expressed in diabetic foot skin,and the mRNA level was decreased(P＜0.01).(3)Scratch assay results demonstrated that compared with the control group,fibroblast migration ability was significantly enhanced in the angiopoietin-like protein 4 group.CCK-8 assay showed that the absorbance value of fibroblasts in the angiopoietin-like protein 4 group was higher than that of the control group at 24 and 48 hours(P＜0.01,P＜0.001).It is suggested that angiopoietin-like protein 4 can enhance the migration and proliferation of fibroblasts.(4)Ki67 assay results demonstrated that the number of Ki67 positive cells in the angiopoietin-like protein 4 group was significantly more than that in the control group.CCK-8 assay results showed that the absorbance value of endothelial cells in the angiopoietin-like protein 4 group was higher than that of the control group at 24 and 48 hours(P＜0.05,P＜0.001).(5)All findings suggest that angiopoietin-like protein 4 can enhance the proliferation of endothelial cells treated with high glucose.