Traumatic brain injury (TBI) is intricately linked to the most severe clinical manifestations of brain damage. It encompasses dynamic pathological mechanisms, including hemodynamic disorders, excitotoxic injury, oxidative stress, mitochondrial dysfunction, inflammation, and neuronal death. This review provides a comprehensive analysis and summary of biomaterial-based tissue engineering scaffolds and nano-drug delivery systems. As an example of functionalized biomaterials, nano-drug delivery systems alter the pharmacokinetic properties of drugs. They provide multiple targeting strategies relying on factors such as morphology and scale, magnetic fields, pH, photosensitivity, and enzymes to facilitate the transport of therapeutics across the blood-brain barrier and to promote selective accumulation at the injury site. Furthermore, therapeutic agents can be incorporated into bioscaffolds to interact with the biochemical and biophysical environment of the brain. Bioscaffolds can mimic the extracellular matrix environment, regulate cellular interactions, and increase the effectiveness of local treatments following surgical interventions. Additionally, stem cell-based and exosome-dominated extracellular vesicle carriers exhibit high bioreactivity and low immunogenicity and can be used to design therapeutic agents with high bioactivity. This review also examines the utilization of endogenous bioactive materials in the treatment of TBI.

Objective To establish an UPLC-MS/MS method for determinating content of three paclitaxel fatty acid esters such as paclitaxel myristate(PTX-MA),paclitaxel palmitate(PTX-PA)and paclitaxel myristate(PTX-SA)in mouse plasma,and preliminarily investigate the pharmacokinetic characteristics of their liposomes in mice.Methods Eclipse Plus C8 chromatography column(2.1 mm×50 mm,1.8 μm)was used with different proportions of 0.2%formic acid aqueous solution(A)and methanol(B)mixture as mobile phase for gradient elution at a flow rate of 0.3 ml/min.The collum temperature was 30℃.The sample injection volume was 10 μl.The triple quadrupole mass series spectrometer was used as multi-reaction monitoring(MRM).Results PTX-MA,PTX-PA and PTX-SA all exhibited a good linear relationship in the range of 5.0～500.0 ng/ml(r>0.995 0).Their RSD of precision,stability,extraction recovery rate and matrix effect test results was all less than 10%.The half-lives(t1/2)for liposomes of three paclitaxel fatty acid esters PTX-MA-L、PTX-PA-L and PTX-SA-L in mice were 14.78 h,44.49 h and 69.32 h individually,and their clearance rates(CL)were 29.06 L?kg/h,24.94 L?kg/h and 13.74 L?kg/h,respectively.Conclusion This method had high specificity,sensitivity,easy operation and good stability,which could be used for the determination of paclitaxel fatty acid esters in mouse plasma.The results of pharmacokinetic studies in mice showed that t1/2 for paclitaxel fatty acid esters were significantly prolonged,and the clearance rate were significantly reduced with the length of fatty acid carbon chains increasement,which indicated that esterification of paclitaxel with different chain length saturated fatty acids could obviously alter its in vivo pharmacokinetic properties,which provided scientific basis for the research and development of nano formulations of paclitaxel fatty acid ester prodrug.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To evaluate the significance of the lumbar bowstring ratio (LBR) and sagittal spine-pelvis parameters in predicting postoperative neurogenic pain in adult patients with high-grade lumbar isthmic spondylolisthesis following spinal fusion surgery.Methods:A retrospective analysis was conducted on the clinical and imaging data of 95 adult patients with high-grade lumbar isthmic spondylolisthesis treated by spinal surgery at Xiangya Hospital of Central South University from August 2012 to January 2023. Each patient was followed for a minimum of six months. Participants were categorized into pain and non-pain groups based on the presence of persistent radicular pain (≥8 weeks) and a visual analogue scale (VAS) score of ≥3 postoperatively. The pain group comprised 15 patients (5 males, 10 females; mean age 55.47±6.42 years, range 46-71 years), while the non-pain group included 80 patients (20 males, 60 females; mean age 60.98±11.50 years, range 40-85 years). Clinical outcomes were assessed using the Oswestry Disability Index (ODI) and VAS scores. LBR was defined as the ratio of the vertical distance from the anterior convexity of the L 1-L 5 anterior longitudinal ligament to a line connecting the posterior superior margin of the L1 vertebra and the posterior margin of the S1 vertebra, to the distance between these two points. Spinal-pelvic parameters measured included pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), PT/SS ratio, and changes in LBR before and after surgery (ΔLBR). Statistical comparisons of demographic and imaging parameters were performed between the two groups, and variables showing significant differences were subjected to binary logistic regression analysis to identify independent risk factors for postoperative neurogenic pain. Results:All 95 patients achieved complete anatomical reduction of the dislocation without reported wound infections. Follow-up was completed at 7.68±2.98 months (range 6-12 months) postoperatively. Among the patients, 15 developed iatrogenic radicular pain. Postoperative complications included pulmonary infection (4 cases: 1 in the pain group, 3 in the non-pain group), cerebrospinal fluid leakage (8 cases: 2 in the pain group, 6 in the non-pain group), and delirium (5 cases: 2 in the pain group, 3 in the non-pain group). No significant differences were observed in demographic data between the groups ( P>0.05). Both groups demonstrated significant improvements in ODI (pain group Z=-3.413, P=0.001; non-pain group Z=-7.772, P<0.001) and VAS scores (pain group Z=-3.426, P=0.001; non-pain group Z=-7.838, P<0.001) at the 6-month follow-up compared to preoperative values. Significant differences were found between the pain and non-pain groups in PI ( t=3.315, P=0.004), PT ( t=5.087, P<0.001), SS ( t=7.431, P<0.001), LL ( t=3.764, P<0.001), PT/SS ( t=7.267, P<0.001), LBR ( t=6.455, P<0.001), and ΔLBR ( Z=5.362, P<0.001) before and after surgery. Binary logistic regression analysis identified smaller preoperative PT/SS [ OR=0.760, 95% CI(0.601, 0.961), P=0.022] and larger preoperative LBR [ OR=5.721, 95% CI (1.068, 30.634), P=0.042] as independent risk factors for postoperative neurogenic pain. Conclusion:High LBR and reduced PT/SS are significant risk factors for neurogenic pain following complete discectomy and fusion in adult patients with high-grade lumbar isthmic spondylolisthesis. For such patients, careful consideration is warranted regarding anatomical complete reduction during surgical intervention.

Objective:To investigate the effect of interleukin-25(IL-25)on ovalbumin(OVA)in-duced atopic dermatitis of mice,and the significance of regulating IL-25.Methods:In this study,90 healthy male 6-week-old specific pathogen free(SPF)BALB/c mice were divided into 6 groups(15 in each group):① subcutaneous injection of phosphate buffered saline(PBS)group(normal control group);② subcutaneous injection of mouse IL-25 group(IL-25 group);③ subcutaneous injection of anti-mouse IL-25 monoclonal antibody(anti-IL-25 group),each group received subcutaneous injection once a day for 1 week,2 weeks apart,repeated daily subcutaneous injections for 1 week,2 weeks apart,and repeated daily subcutaneous injections for 1 week,for a total of 7 weeks;④OVA treated group(model group);⑤ OVA treated and IL-25 subcutaneous injection group(IL-25 treated dermatitis group);⑥ OVA treated and anti-mouse IL-25 monoclonal antibody injection group(anti-IL-25 treated dermatitis group).The ⑤ and ⑥ groups in the process of treatment with OVA,IL-25 or anti-IL-25 anti-body were given in the same way as the ② and ③ groups.Scratching behavior and skin performance of the mice were recorded during the seven-week-treatment.Twenty four hours after the final treatment,blood was taken from the mouse heart,and the serum was separated to detect the total IgE,IL-4,IL-5,IL-13,etc.The skin samples of the treatment sites were used for hematoxylin-eosin(HE)staining,im-munohistochemistry,real-time PCR and Western blot detections.A single factor(ANOVA)analysis of variance was used to compare the differences in various indicators between the groups.Results:The fre-quency of scratches in the IL-25 treated dermatitis group was higher than that in the model group,and the scratching behavior of the anti-IL-25 treated dermatitis group was significantly lower than that in the model group.The appearance of atopic dermatitis,thickening of the epidermis and the degree of dermal inflammation in the IL-25 treated dermatitis group were more serious than those in the model group and the anti-IL-25 treated dermatitis group.The levels of serum IgE,IL-4,IL-5,and IL-13 in the IL-25 treated dermatitis group were significantly higher than that in the model group and the anti-IL-25 treated dermatitis group.There were significantly more CD4+T cells in the dermis of IL-25 treated dermatitis group than that in the anti-IL-25 treated dermatitis group.The expression levels of filaggrin and defensinβ2 proteins in the IL-25 treated dermatitis group were significantly lower than those in the model group and the anti-IL-25 treated dermatitis group.Conclusion:In the OVA induced atopic dermatitis mice model,IL-25 can significantly promote the damage of the epidermal barrier function and aggravate the OVA-induced dermatitis.Antagonizing IL-25 can alleviate OVA induced dermatitis to a certain extent.

Accurate classification of the acetabular injuries and appropriate treatment plan are great challenges for orthopedic surgeons because of the irregular anatomical structure of the acetabulum and aggregation of important vessels and nerves around it. Letournel-Judet classification system has been widely applied to classify acetabular fractures. However, there are several limitations, including incomplete inclusion of fracture types, difficulty in understanding and insufficient guidance for surgical treatment, etc. Serious complications such as traumatic arthritis are common due to wrong classification and diagnosis and improper selection of surgical strategy, which brings a heavy burden to the society and families. Three-column classification, based on anatomic characteristics, has advantages of containing more fracture types and being easy to understand, etc. To solve the problems existing in the diagnosis and treatment process based on Letournel-Judet classification, achieve accurate diagnosis and treatment of patients with acetabular fractures, and obtain satisfactory prognosis, the Orthopedic Trauma Emergency Center of Third Hospital of Hebei Medical University and the Trauma Orthopedic Branch of the Chinese Orthopedic Association organized experts from relevant fields to formulate the Expert consensus on the accurate diagnosis and treatment of acetabular fractures based on three-column classification ( version 2023) in terms of principles of evidence-based medicine. Based on the three-column classification, 15 recommendations were proposed, covering the diagnosis, treatment, complication prevention and management, etc, so as to provide reference for accurate diagnosis and treatment of acetabular fractures.

Objective:To summarize and analyze clinical characteristics and possible pathogenesis of atopic dermatitis (AD) -like lesions after treatment with interleukin-17 (IL-17) antagonists in patients with psoriasis, so as to improve the clinical management of these patients.Methods:Four patients with psoriasis, who developed AD-like lesions after the treatment with IL-17 antagonists, were reported. A comprehensive update-search was carried out to analyze and summarize clinical characteristics of and therapeutic strategies for other related cases reported in Chinese and international literature.Results:Among the 4 patients in this study, 2 were males and 2 were females, with a history of psoriasis ranging from 10 to 35 years; after 5-month to 2-year treatment with secukinumab, they developed pruritic erythema and papules with exudation on the trunk, limbs and/or face. All the 4 patients had a history of atopic diseases and elevated serum total IgE levels and/or eosinophil counts. AD-like lesions were controlled in 3 patients after treatment with systemic cyclosporine, glucocorticoids and/or antihistamines, as well as topical glucocorticoids and/or tacrolimus, and secukinumab continued to be administered simultaneously; 1 discontinued secukinumab due to repeated AD-like lesions. Totally, 12 articles in English containing 48 patients were included, and a total of 52 patients including the 4 patients in this study were analyzed. Among them, there were 30 males and 22 females, with the age being 50.1 ± 13.6 years; 37 cases were induced by secukinumab, 14 induced by ixekizumab, and 1 induced by brodalumab; the time from the initiation of biologic therapy to the onset of AD-like lesions ranged from 1 week to 2 years; the lesions manifested as pruritic erythema and papules, accompanied by scales or exudation; the skin lesions were mainly distributed on the limbs (41 cases, 78.8%), followed by the trunk (32 cases, 61.5%) and face (20 cases, 38.5%) ; a personal or family history of atopic diseases was reported in 57.7% patients; peripheral blood eosinophil counts increased in 5 cases, and serum total IgE levels were elevated in 17. Thirty-two (61.5%) patients discontinued IL-17 antagonists, and received single or combination therapies, including systemic treatment with cyclosporine, methotrexate, glucocorticoids, antihistamines, other biologic agents and small-molecule drugs, topical treatment with glucocorticoids and/or tacrolimus, and phototherapy; 20 (38.5%) patients continued the previous treatment with IL-17 antagonists, and additionally received topical treatment with or without oral antihistamines or cyclosporine; after the above treatment, the psoriatic and AD-like lesions were controlled in most patients.Conclusions:AD-like lesions after IL-17 antagonist therapy were not common in patients with psoriasis, and these patients developing AD-like lesions were more likely to have a personal or family history of atopic diseases and elevated levels of serum total IgE; based on the disease condition, the treatment with IL-17 antagonists may be considered to continue during the symptomatic treatment of AD-like lesions.