SARS-CoV-2 and its emerging variants continue to pose a significant global public health threat. The SARS-CoV-2 main protease (M^pro) is a critical target for the development of antiviral agents that can inhibit viral replication and transcription. In this study, we identified chebulagic acid (CHLA), isolated from Terminalia chebula Retz., as a potent non-peptidomimetic and non-covalent M^pro inhibitor. CHLA exhibited intermolecular interactions and provided significant protection to Vero E6 cells against a range of SARS-CoV-2 variants, including the wild-type, Delta, Omicron BA.1.1, BA.2.3, BA.4, and BA.5, with EC₅₀ values below 2 μmol/L. Moreover, in vivo studies confirmed the antiviral efficacy of CHLA in K18-hACE2 mice. Notably, CHLA bound to a unique groove at the interface between M^pro domains I and II, which was revealed by the high-resolution crystal structure (1.4 Å) of the M^pro-CHLA complex, shrinking the substrate binding pocket of M^pro and inducing M^pro aggregation. CHLA was proposed to act as an allosteric inhibitor. Pharmacokinetic profiling and safety assessments underscore CHLA's potential as a promising broad-spectrum antiviral candidate. These findings report a novel binding site on M^pro and identify antiviral activity of CHLA, providing a robust framework for lead compounds discovery and elucidating the underlying molecular mechanisms of inhibition.

Objective:To evaluate the clinical effect of different types of aortic root replacement in adolescent patients with aortic root aneurysm by analyzing the perioperative and follow-up conditions of surgical treatment for adolescent aortic root aneurysm.Methods:The clinical data of patients aged ≤18 years who were admitted to the Beijing Anzhen Hospital from November 2012 to February 2025, diagnosed with aortic root aneurysm by ultrasound or aortic computed tomography angiography (CTA) and requiring surgical intervention, were collected retrospectively. They were divided into the valve-sparing aortic root replacement group (David operation group) and the aortic root replacement group (Bentall operation group) according to the surgical method. The perioperative results and long-term follow-up results of the two groups were analyzed. Kaplan-Meier survival curves were drawn to compare the reoperation intervention rate between the two groups.Results:A total of 25 patients were included in this study, including 17 in the Bentall group and 8 in the David group. There were no statistically significant differences in gender, age, blood routine, liver and kidney function, coagulation function, and electrolyte internal environment between the two groups (all P>0.05). There were no statistically significant differences in operation time and intensive care unit stay between the two groups (all P>0.05). Compared with the Bentall operation group, the intraoperative blood loss in the David operation group was more ( P<0.05). During the follow-up, no reoperation occurred in the Bentall operation group, while 3 patients in the David operation group had long-term re-intervention. The long-term reoperation intervention rate in the David operation group was higher than that in the Bentall group ( P=0.042), but there was no statistically significant difference in the aortic valve-related surgical intervention rate between the two groups ( P=0.15). Conclusions:For adolescent patients with aortic root aneurysm, although David operation may face long-term reoperation intervention, this intervention may not be due to the difference in surgical methods. Both Bentall operation and David operation are safe and reliable, with good perioperative results and stable medium and long-term prognosis.

Objective:To evaluate the efficacy, safety, and prognostic factors of transarterial chemoembolization (TACE) combined with molecular targeted therapy (MTT) and camrelizumab in patients with unresectable recurrent hepatocellular carcinoma (urHCC).Methods:Clinical data of 83 patients with urHCC treated at the First Affiliated Hospital of the University of Science and Technology of China between October 2018 and October 2023 were retrospectively analyzed, including 75 males and 8 females, aged (55.2±10.7) years. Among them, 43 patients received TACE combined with MTT and camrelizumab (observation group), while 40 received TACE combined with MTT alone (control group). Kaplan-Meier curves were plotted to compare overall survival (OS) and progression-free survival (PFS) between the groups. Treatment response was assessed according to the mRECIST criteria, and objective response rate (ORR) and disease control rate (DCR) were compared. Adverse events (AEs) were monitored in both groups.Results:The observation group demonstrated longer median OS (31.8 vs 19.9 months, χ2=11.26, P=0.001) and median PFS (14.5 vs 7.4, months, χ2=4.08, P=0.043) compared to the control group. The ORR and DCR in the observation group were 51.2% (22/43) and 90.1% (39/43), respectively, both higher than those in the control group [25.0% (10/40) and 70.0% (28/40), respectively]. The differences were statistically significant ( χ2=5.99, 5.71; P=0.023, 0.025; respectively). Multivariate Cox analysis showed that different treatment regimens were influencing factors for post-treatment survival in patients with urHCC (control group vs treatment group: HR=2.633, 95% CI: 1.483- 4.677, P<0.001), as well as for PFS (control group vs treatment group: HR=1.781, 95% CI: 1.116-2.842, P=0.015). No treatment-related deaths or unexpected AEs occurred in either group. The most common systemic therapy-related AE was hand-foot syndrome, observed in 15 patients (34.9%, 15/43) in the observation group and 9 (22.5%, 9/40) in the control group ( χ2=1.55, P=0.236). Conclusions:Compared to TACE combined with MTT alone, TACE combined with MTT and camrelizumab demonstrates superior efficacy and acceptable safety in treating unresectable recurrent HCC.

BACKGROUND:Facet joint osteoarthritis is acknowledged as a significant contributor to lower back pain in the geriatric population.The advent of an innovative spinal facet joint fusion device presents a therapeutic option for intervening during the initial stages of facet joint osteoarthritis,and significantly reduces the incidence of a series of complications caused by poor early conservative treatment and late surgical treatment.However,its effect on the biomechanics of the lumbar spine is unknown.OBJECTIVE:To investigate the biomechanical disparities between the novel lumbar zygapophyseal joint fusion device and traditional fusion devices.METHODS:A comprehensive three-dimensional finite element model of the L3-S1 lumbar spine was established and validated.Based on this intact model,three groups of surgical models were constructed:a bilateral pedicle screw fixation model,a bilateral novel facet joint fusion fixation model,and a bilateral facet screw fixation model,with the surgical segment designated as L4-5.Under a load of 500 N,a torque of 7.5 Nm was applied to all lumbar models to calculate the range of motion,displacement values,and intervertebral disc stress values at the L4-5 segment;stress values at the L3-4 and L5-S1 segments were also measured.RESULTS AND CONCLUSION:(1)Compared with the intact model,the range of motion at the L4-5 segment was reduced in all surgical models.(2)The novel device exhibited the smallest range of motion at the L4-5 segment under left and right rotational conditions;the greatest range of motion at the L4-5 segment under extension conditions;and a greater range of motion under other conditions than the bilateral pedicle screw fixation model.(3)The novel device demonstrated the smallest displacement values at the L4-5 segment under left and right rotational conditions;under other conditions,the displacement values at the L4-5 segment were greater than those in the bilateral pedicle screw fixation model.(4)In terms of stress distribution at the L4-5 segment,the novel device consistently exhibited the smallest values across all conditions.(5)For the L3-4 segment,the novel device showed the greatest stress values under extension and left and right rotational conditions,while under other conditions,the values were lower than those in the bilateral pedicle screw fixation model.(6)Compared with pedicle screw fixation,the novel device produced smaller stress values at the L5-S1 segment.(7)This study indicates that,compared with pedicle screw fixation,the novel device impacts the biomechanics of the lumbar spine by fusing the facet joints.It provides stability while preserving the range of motion at the surgical segment and reduces stress on the intervertebral discs of the surgical and adjacent segments,thereby potentially delaying disc degeneration.This suggests that the novel device can achieve biomechanical effects similar to those of pedicle screw fixation in theory.

OBJECTIVE: To investigate the role of α7-nicotinic acetylcholine receptor (α7-nAChR) in the regulation of neuronal activity and expression of synapse-related proteins in the thalamic reticular nucleus (TRN) of insomnia rats treated by acupuncture. METHODS: A total of 36 male Sprague-Dawley (SD) rats of clean grade were randomly divided into a control group, a model group, an acupuncture group, and an acupuncture+antagonist group, with 9 rats in each group. The model group, the acupuncture group, and the acupuncture+antagonist group were treated with intraperitoneal injection of p-chlorophenylalanine (PCPA) to establish insomnia model. After successful modeling, the acupuncture group and the acupuncture+antagonist group received acupuncture at bilateral Neiguan (PC6) and Zusanli (ST36) once daily for 5 consecutive days. Thirty min before each acupuncture session, the acupuncture+antagonist group was intraperitoneally injected with methyllycaconitine citrate (MLA), an α7-nAChR antagonist, at a dosage of 5 mg/kg while the acupuncture group received the same volume of 0.9% sodium chloride solution. The rats' daytime spontaneous activity was observed. Neuronal discharge in the TRN was detected using neuroelectrophysiological methods. Immunofluorescence staining was used to detect parvalbumin-positive (PV⁺) neurons and co-expression of PV⁺ and postsynaptic density protein-95 (PSD-95) in the TRN. RESULTS: Compared with the control group, the model group showed increased daytime spontaneous activity (P<0.01); decreased average fluorescence intensity and positive number of PV⁺ neurons in the TRN (P<0.01); decreased neuronal discharge frequency (P<0.01), prolonged inter-discharge intervals (P<0.01) in the TRN; reduced number of PV⁺/PSD-95 double-positive cells in the TRN (P<0.01). Compared with the model group, the acupuncture group showed decreased daytime spontaneous activity (P<0.01); increased average fluorescence intensity and positive number of PV⁺ neurons in the TRN (P<0.01); increased neuronal discharge frequency (P<0.01), shortened inter-discharge intervals (P<0.01) in the TRN; increased number of PV⁺/PSD-95 double-positive cells in the TRN (P<0.05). Compared with the acupuncture group, the acupuncture+antagonist group exhibited increased daytime spontaneous activity (P<0.01); reduced average fluorescence intensity and positive number of PV⁺ neurons in the TRN (P<0.01); decreased neuronal discharge frequency (P<0.05), prolonged inter-discharge intervals (P<0.05) in the TRN; reduced number of PV⁺/PSD-95 double-positive cells in the TRN (P<0.01). CONCLUSION α7-nAChR are involved in mediating the regulatory effect of acupuncture on circadian rhythm disturbances in PCPA-induced insomnia rats. Blocking α7-nAChR attenuates the activating effect of acupuncture on TRN neurons, and reduces the expression of PSD-95 protein on GABAergic neurons.
Animals ; Male ; Acupuncture Therapy ; alpha7 Nicotinic Acetylcholine Receptor/genetics* ; Rats, Sprague-Dawley ; Rats ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Neurons/metabolism* ; Humans ; Thalamic Nuclei/physiopathology* ; Acupuncture Points ; Disks Large Homolog 4 Protein

Objective:To evaluate the clinical value of sacral canal posterior wall reconstruction in the treatment of symptomatic sacral canal cysts.Methods:A retrospective cohort study was conducted.The clinical data of 80 patients with symptomatic sacral cysts who underwent surgical treatment at Beijing Friendship Hospital, Capital Medical University, between June 2018 and September 2024 were collected. There were 19 males and 61 females, with an average age of (49.0±11.3) years (ranged from 23-76 years). The patients were divided into the traditional group ( n=30) and the reconstruction group ( n=50) based on the surgical approach. The traditional group underwent the conventional surgical method without reconstruction of the posterior wall of the sacral canal, while the reconstruction group underwent posterior wall reconstruction of the sacral canal. Postoperative observations included the integrity of the sacral canal posterior wall, wound healing, and symptom improvement in both groups. Measurement data with normal distribution were expressed as mean±standard deviation( ± s). Independent samples t-test was used for comparisons of measurement data between groups. Categorical data were compared using the chi-square test or Fisher′s exact test. Ordinal data were analyzed using the Mann-Whitney U test. Pearson correlation analysis was used to assess the relationship between variables. Results:Among the 80 patients, the sacral bone integrity score in the reconstruction group was (1.42±0.49) scores, compared to (3.00±0.00) scores in the traditional group, the reconstruction group showed significantly better results ( P<0.05). Symptom improvement was also significantly different between the two groups ( P=0.038): in the traditional group, 17 patients experienced complete symptom resolution, 6 partial improvement, 7 no improvement, and 0 worsening; in the reconstruction group, 37 had complete symptom resolution, 11 partial improvement, 2 no improvement, and 0 worsening. The effective improvement rate (complete+ partial improvement) in the reconstruction group was significantly better than that in the traditional group ( P=0.012). In terms of wound healing, 76 cases healed well, 4 had delayed healing, and 0 had infections. In the traditional group, 27 healed well, 3 had delayed healing, 0 infections; in the reconstruction group, 49 healed well, 1 had delayed healing, and 0 infections. There was no significant difference in wound healing rate between the two groups ( P=0.146). A significant positive correlation was found between sacral canal posterior wall integrity and symptom improvement ( r=0.288, P=0.010). Conclusion:Sacral canal posterior wall reconstruction significantly improves postoperative anatomical integrity and clinical outcomes without increasing complications, supporting its adoption as a preferred surgical approach for symptomatic sacral canal cysts.

Contralateral radiculopathy, a postoperative complication after transforaminal lumbar interbody fusion, refers to postoperative numbness, pain and other neurological symptoms of the lower limb on the side opposite to the symptomatic or the surgical decompression side. Its main causes include excessive restoration of lordosis, intervertebral space tilt caused by improper cage position, poor screw position, new protrusion of nucleus pulposus or bone graft, and hematoma. At present, attention to this complication is gradually increasing. This review summarizes its risk factors from the recent related reports of the condition and puts forward preventive measures in order to promote the preventive awareness of this complication.

Neurodegenerative diseases are a group of disorders characterized by progressive and chronic degeneration of neurons in the central or peripheral nervous system,primarily including conditions such as amyotrophic lateral sclerosis,frontotemporal dementia,Alzheimer's disease,Parkinson's disease,multiple sclerosis,Huntington's disease and age-related macular degeneration.The condition worsens over time,ultimately leading to neuronal loss and synaptic dysfunction.Despite significant advances in medical research,the diagnosis and treatment of neurodegenerative diseases still face major challenges.There is an urgent need for effective and innovative treatment strategies as well as early monitoring methods.This involves not only new drug targets but also research into disease mechanisms.Neuronal pentraxin 2(NPTX2)is a protein expressed in the nervous system,highly expressed in synaptic regions of the brain,where it plays a critical role in synaptic plasticity and the formation and maintenance of neural networks.This paper reviews the role of NPTX2 in neurodegenerative diseases and summarizes recent research progress.

Erectile Dysfunction(ED)is a relatively common clinical condition characterized by male sexual dysfunction.Macrophages,as key components of the immune and inflammatory response systems,play crucial roles in immune surveillance,tissue repair,and the maintenance of tissue homeostasis in processes related to erectile function.Immune inflammation is recognized as one of the pathological factors contributing to ED,and inflammatory markers—including macrophages—are widely believed to be closely associated with the onset of the disorder.This review summarizes the multifaceted roles of macrophages in vascular injury,neural repair,hormonal balance,and immune microenvironment remodeling in the context of erection.It aims to provide a theoretical foundation for further investigation into the involvement of macrophages in ED and discusses the potential of macrophage-targeted therapies for treating ED.

Erectile Dysfunction(ED)is a relatively common clinical condition characterized by male sexual dysfunction.Macrophages,as key components of the immune and inflammatory response systems,play crucial roles in immune surveillance,tissue repair,and the maintenance of tissue homeostasis in processes related to erectile function.Immune inflammation is recognized as one of the pathological factors contributing to ED,and inflammatory markers—including macrophages—are widely believed to be closely associated with the onset of the disorder.This review summarizes the multifaceted roles of macrophages in vascular injury,neural repair,hormonal balance,and immune microenvironment remodeling in the context of erection.It aims to provide a theoretical foundation for further investigation into the involvement of macrophages in ED and discusses the potential of macrophage-targeted therapies for treating ED.