OBJECTIVE To explore the pharmacokinetic characteristics of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with hyperplasia of mammary gland （HMG）. METHODS Female SD rats were divided into control group and HMG group according to body weight， with 6 rats in each group. The HMG group was given estrogen+progesterone to construct HMG model. After modeling， two groups were given 1.485 g/kg of Xiangshao sanjie oral liquid （calculated by crude drug） intragastrically， once a day， for 7 consecutive days. Blood samples were collected before the first administration （0 h）， and at 5， 15， 30 minutes and 1， 2， 4， 8， 12， 24 hours after the last administration， respectively. Using chlorzoxazone as the internal standard， the plasma concentrations of ferulic acid， paeoniflorin and rosmarinic acid in rats were detected by UPLC-Q/TOF-MS. The pharmacokinetic parameters [area under the drug time curve （AUC0－24 h， AUC0－∞）， mean residence time （MRT0－∞）， half-life （t1/2）， peak time （tmax）， peak concentration （cmax）] were calculated by the non-atrioventricular model using Phoenix WinNonlin 8.1 software. RESULTS Compared with the control group， the AUC0－24 h， AUC0－∞ and cmax of ferulic acid in the HMG group were significantly increased （P＜0.05）； the AUC0－24 h， AUC0－∞ ， MRT0－∞ ， t1/2 and cmax of paeoniflorin increased， but there was no significant difference between 2 groups （P＞0.05）； the AUC0－24 h and MRT0-∞ of rosmarinic acid were significantly increased or prolonged （P＜0.05）. C ONCLUSIONS In HMG model rats， the exposure of ferulic acid， paeoniflorin and rosmarinic acid in Xiangshao sanjie oral liquid all increase， and the retention time of rosmarinic acid is significantly prolonged.

Objective: To analyze the factors associated with high level fear of negative evaluation (FNE) among junior high school students and to construct a nomogram risk prediction model, so as to provide scientific tools for psychological health intervention for junior high school students. Methods: A convenience sampling combined with cluster random sampling method was used to select 5 485 junior high school students from 4 cities (Wuhan, Huanggang, Xianning and Xiaogan) for an online questionnaire survey in March 2025. The total sample was randomly split into a training set ( n =3 839) and a validation set ( n =1 646). Univariate analysis was performed in the training set using Chi-square test and t-test. Variables with statistical significance were subsequently included in multivariate Logistic regression to identify independent predictors and to construct a nomogram based risk prediction model. The discriminative ability and clinical utility of the model were evaluated in the validation set using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: There were 1 649 junior high school students with low level FNE and 2 190 with high level FNE in the training set. The self control ability of junior high school students with lowlevel and high level FNE showed a statistically significant difference (23.96±3.96, 21.48±3.37, t=25.15, P < 0.01 ). Statistically significant differences in the detection rate of high level FNE were observed among junior high school students with different genders, family types, parenting styles, academic rankings, psychological flexibility, mobile phone addiction tendencies, emotional management training, exercise frequency, left behind experiences, and places of origin ( χ 2=82.01- 1 126.68 , all P <0.01). The results of Logistic regression analysis revealed that, the following factors were identified as significant factors influencing high level FNE among junior high school students:exercise frequency ( OR=0.21, 95%CI =0.17-0.26); parenting style ( OR=0.48, 95%CI =0.40-0.58); left behind experience ( OR=3.88, 95%CI =3.27-4.61); smartphone addiction proneness ( OR=2.19, 95%CI =0.89-0.93); self-control ability ( OR=0.91, 95%CI =0.89-0.93); and psychological flexibility ( OR=0.16, 95%CI =0.10-0.28) (all P <0.05). The AUC for the training and validation set were 0.88 (95% CI =0.87-0.89) and 0.87 (95% CI =0.85-0.89), respectively. The Hosmer-Lemeshow goodness of fit test yielded χ 2=8.57, 15.20 (both P >0.05). Conclusion The risk prediction model with high level FNE demonstrates good accuracy and can assist educators and parents in timely screening of junior high school students with high level FNE, thereby providing a basis for implementing targeted interventions.

Collagen-based materials, renowned for their biocompatibility and minimal immunogenicity, serve as exemplary substrates in a myriad of biomedical applications. Collagen-based micro/nanogels, in particular, are valued for their increased surface area, tunable degradation rates, and ability to facilitate targeted drug delivery, making them instrumental in advanced therapeutics and tissue engineering endeavors. Although extensive reviews on micro/nanogels exist, they tend to cover a wide range of biomaterials and lack a specific focus on collagen-based materials. The current review offers an in-depth look into the manufacturing technologies, drug release mechanisms, and biomedical applications of collagen-based micro/nanogels to address this gap. First, we provide an overview of the synthetic strategies that allow the precise control of the size, shape, and mechanical strength of these collagen-based micro/nanogels by controlling the degree of cross-linking of the materials. These properties are crucial for their performance in biomedical applications. We then highlight the environmental responsiveness of these collagen-based micro/nanogels, particularly their sensitivity to enzymes and pH, which enables controlled drug release under various pathological conditions. The discussion then expands to include their applications in cancer therapy, antimicrobial treatments, bone tissue repair, and imaging diagnosis, emphasizing their versatility and potential in these critical areas. The challenges and future perspectives of collagen-based micro/nanogels in the field are discussed at the end of the review, with an emphasis on the translation to clinical practice. This comprehensive review serves as a valuable resource for researchers, clinicians, and scientists alike, providing insights into the current state and future directions of collagen-based micro/nanogel research and development.
Collagen/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Tissue Engineering/methods* ; Animals ; Biocompatible Materials/chemistry*

Objective The study aims to investigate the immunological functions of the nucleocapsid (N) protein of the novel coronavirus Omicron (BA.1, BA.2) and evaluate the differences among different N proteins of mutant strains in immunogenicity. Methods By aligning sequences, the mutation sites of the Omicron (BA.1, BA.2) N protein relative to prototype strain of the novel coronavirus (Wuhan-Hu-1) were determined. The pET-28a-N-Wuhan-Hu-1 plasmid was used as template to construct pET-28a-BA.1/BA.2-N through single point mutation or homologous recombination. The three kinds of N protein were expressed in prokaryotic system, purified through Ni-NTA affinity chromatography, and then immunized into mice. The titer and reactivity of the polyclonal antibody, as well as the expression level of IL-1β and IFN-γ in mouse spleen cells, were detected using indirect ELISA and Western blot assay. Results The constructed prokaryotic expression plasmids were successfully used to express the Wuhan-Hu-1 N, BA.1 N, and BA.2 N proteins in E.coli BL21(DE3) at 37 DegreesCelsius for 4 hours. The indirect ELISA test showed that the titers of polyclonal antibody prepared by three N proteins were all 1:51 200. All three N proteins can increase the expression of IFN-γ and IL-1β cytokines, but the effect of Omicron N protein in activing two cytokines was more obvious than that of Wuhan-Hu-1 N protein. Conclusion The study obtained three new coronavirus N proteins and polyclonal antibodies, and confirmed that mutations in the amino acid sites of the N protein can affect its immunogenicity. This provides a basis for developing rapid diagnostic methods targeting N protein of different novel coronavirus variants.
Animals ; Mice ; SARS-CoV-2/genetics* ; Coronavirus Nucleocapsid Proteins/immunology* ; Nucleocapsid Proteins/isolation & purification* ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Mice, Inbred BALB C ; Interferon-gamma/metabolism* ; Interleukin-1beta/metabolism* ; Female ; Escherichia coli/metabolism* ; Mutation ; Humans

PURPOSE: Traumatic brain injury (TBI) is a significant public health issue that impacts individuals all over the world and is one of the main causes of mortality and morbidity. Decompressive craniectomy is the usual course of treatment. Basal cisternostomy has been shown to be highly effective as an alternative procedure to decompressive craniectomy. METHODS: We conducted a retrospective cohort of patients who received surgery for severe TBI between January 2019 and March 2023. Inclusion criterias were patients between the ages of 18 and 70 years who met the diagnostic criteria for severe TBI at first presentation and who underwent surgical intervention. The exclusion criteria were patients who have severe multiple injuries at the time of admission; preoperative intracranial pressure > 60 mmHg; cognitive impairment before the onset of the disease; hematologic disorders; or impaired functioning of the heart, liver, kidneys, or other visceral organs. Depending on the surgical approach, the patients were categorized into decompressive craniectomy group as well as basal cisternostomy group. General data and postoperative indicators, including Glasgow coma scale, intracranial pressure, etc., were recorded for both groups of patients. Among them, the Glasgow outcome scale extended assessment at 6 months served as the primary outcome. After that, the data were statistically analyzed using SPSS software. RESULTS: The trial enrolled 41 patients (32 men and 9 women) who met the inclusion criteria. Among them, 25 patients received decompressive decompressive craniectomy, and 16 patients received basal cisternostomy. Three days postoperative intracranial pressure levels were 10.07 ± 2.94 mmHg and 17.15 ± 14.65 mmHg (p = 0.013), respectively. The 6 months following discharge Glasgow outcome scale extended of patients was 4.73 ± 2.28 and 3.14 ± 2.15 (p = 0.027), respectively. CONCLUSION Our study reveals that basal cisternostomy in patients with surgically treated severe TBI has demonstrated significant efficacy in reducing intracranial pressure as well as patient prognosis follow-up and avoids removal of the bone flap. The efficacy of cisternostomy has to be studied in larger, multi-clinical center randomized trials.
Humans ; Brain Injuries, Traumatic/surgery* ; Retrospective Studies ; Male ; Female ; Adult ; Middle Aged ; Decompressive Craniectomy/methods* ; Aged ; Young Adult ; Adolescent ; Glasgow Coma Scale ; Treatment Outcome

With the advancement of rigid endoscopic nasal surgery techniques, the indications for surgery have continued to expand, encompassing an increasing number of anatomical regions. As a surgical adjunct, imaging-guided system assists surgeons in identifying vital structures and mitigating surgical risks, and they are extensively employed in operations involving the nasal cavity, sinuses, and skull base. Nevertheless, existing imaging-guided system faces several unresolved challenges. With ongoing technological advancements and the integration of novel technologies, these systems are demonstrating renewed vigor.
Humans ; Skull Base/surgery* ; Endoscopy/methods* ; Surgery, Computer-Assisted/methods*

Triggering receptor expressed on myeloid cells 2 (TREM2)-mediated microglial phagocytosis is an energy-intensive process that plays a crucial role in amyloid beta (Aβ) clearance in Alzheimer's disease (AD). Energy metabolic reprogramming (EMR) in microglia induced by TREM2 presents therapeutic targets for cognitive impairment in AD. Jiawei Xionggui Decoction (JWXG) has demonstrated effectiveness in enhancing energy supply, protecting microglia, and mitigating cognitive impairment in APP/PS1 mice. However, the mechanism by which JWXG enhances Aβ phagocytosis through TREM2-mediated EMR in microglia remains unclear. This study investigates how JWXG facilitates microglial phagocytosis and alleviates cognitive deficits in AD through TREM2-mediated EMR. Microglial phagocytosis was evaluated through immunofluorescence staining in vitro and in vivo. The EMR level of microglia was assessed using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits. The TREM2/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway was analyzed using Western blotting in BV₂ cells. TREM2^-/- BV₂ cells were utilized for reverse validation experiments. The Aβ burden, neuropathological features, and cognitive ability in APP/PS1 mice were evaluated using ELISA kits, immunohistochemistry (IHC), and the Morris water maze (MWM) test. JWXG enhanced both the phagocytosis of EMR disorder-BV₂ cells (EMRD-BV₂) and increased EMR levels. Notably, these effects were significantly reversed in TREM2^-/- BV₂ cells. JWXG elevated TREM2 expression, adenosine triphosphate (ATP) levels, and microglial phagocytosis in APP/PS1 mice. Additionally, JWXG reduced Aβ-burden, neuropathological lesions, and cognitive deficits in APP/PS1 mice. In conclusion, JWXG promoted TREM2-induced EMR and enhanced microglial phagocytosis, thereby reducing Aβ deposition, improving neuropathological lesions, and alleviating cognitive deficits.
Drugs, Chinese Herbal/pharmacology* ; Microglia/drug effects* ; Phagocytosis ; Cognitive Dysfunction/drug therapy* ; Metabolic Reprogramming ; Animals ; Mice ; Cell Line ; Receptors, Immunologic/metabolism* ; Membrane Glycoproteins/metabolism* ; Signal Transduction ; Amyloid beta-Peptides/metabolism* ; Energy Metabolism

Vaccination is a crucial strategy for the prevention and control of infectious diseases. Virus-like particles (VLPs), composed of structural proteins, have garnered significant attention as a novel type of vaccine due to their excellent safety and immunogenicity. However, similar to most vaccine antigens, VLPs exhibit insufficient thermal stability, which not only restricts the widespread application of vaccines but also increases the risk of vaccine inactivation. This study aims to enhance the stability and shelf life of VLPs derived from type A foot-and-mouth disease virus (FMDV) by employing vacuum freeze-drying technology. The optimal lyoprotectant formulation was determined through single-factor and combinatorial screening. Subsequently, the correlation between the immunogenicity of the freeze-dried vaccine and the content of FMDV VLPs was evaluated via a mouse model. The stability of FMDV VLPs before and after freeze-drying was further assessed by storing them at 4, 25, and 37 ℃ for varying time periods. Results indicated that the lyoprotectant formulation No.1, composed of 7.5% trehalose, 0.1% Tween 80, 50 mmol/L glycine, 1% sodium glutamate, and 3% polyvinylpyrrolidone (PVP), effectively preserved the content of FMDV VLPs during the vacuum freeze-drying process. The immunization trial in mice revealed that the levels of specific antibodies, immunoglobulin G1 (IgG1), interleukin-4 (IL-4), and neutralizing antibodies induced by freeze-dried FMDV VLPs were comparable to those induced by non-freeze-dried FMDV VLPs. The heat treatment results showed that the storage periods of freeze-dried FMDV VLPs at 4, 25, and 37 ℃ were significantly longer than those of non-freeze-dried FMDV VLPs. In conclusion, the selected lyoprotectant formulation effectively improved the stability of FMDV VLPs vaccines. This study provides valuable insights for enhancing the stability of novel subunit vaccines.
Freeze Drying/methods* ; Animals ; Foot-and-Mouth Disease Virus/immunology* ; Mice ; Vaccines, Virus-Like Particle/chemistry* ; Foot-and-Mouth Disease/immunology* ; Vacuum ; Drug Stability ; Mice, Inbred BALB C ; Viral Vaccines/immunology*

Pseudorabies (PR) is an infectious disease caused by the pseudorabies virus (PRV), affecting various domesticated and wild animals. Since pigs are the only natural hosts of PRV, PR poses a serious threat to the pig farming industry. Currently, PR is primarily prevented through vaccination with inactivated vaccines or genetically modified attenuated live vaccines. Developing safe and effective genetically engineered vaccines would facilitate the eradication and control of PR. In this study, the PRV vaccine strain Bartha-K61 was used as the reference strain. The gB protein was expressed via the baculovirus-insect cell expression system. Non-denaturing gel electrophoresis confirmed that the gB protein could form a trimeric structure. The purified gB protein was used to immunize mice, and the immune effect was evaluated by a challenge test. The results showed that the gB antigen induced a strong immune response in mice, with the serum-neutralizing antibody titer above 1:70. The lymphocyte stimulation index reached more than 1.29, and the level of (interferon gamma, IFN-γ) release was higher than 100 pg/mL. After immunization, mice were challenged with the virus at a dose of 10⁴ TCID₅₀/mL, 200 μL per mouse, and the clinical protection rate was 100%. Immunohistochemistry, histopathological section, and tissue viral load results showed that the pathological damage and viral load in the gB-immunized group were significantly lower than those in the PBS group. In summary, the gB protein obtained in this study induced strong humoral and cellular immune responses in mice, laying a foundation for developing a recombinant gB protein subunit vaccine.
Animals ; Mice ; Baculoviridae/metabolism* ; Viral Envelope Proteins/biosynthesis* ; Herpesvirus 1, Suid/genetics* ; Pseudorabies/immunology* ; Swine ; Pseudorabies Vaccines/genetics* ; Antibodies, Viral/blood* ; Insecta/cytology* ; Mice, Inbred BALB C ; Female ; Viral Vaccines/immunology*

Objective:To evaluate and compare dermoscopic features of toenail psoriasis and fingernail psoriasis.Methods:Between June 2020 and January 2022, 61 patients with confirmed toenail psoriasis and 80 with confirmed fingernail psoriasis were enrolled from the Department of Dermatology of Peking University First Hospital. Dermoscopy was performed on 139 affected toenails and 158 affected fingernails among the psoriasis patients, and dermoscopic characteristics were analyzed between the two groups by using the chi-square test.Results:The most common dermoscopic feature of nail psoriasis was pitting (223/297, 75.08%), followed by splinter haemorrhages (164/297, 55.22%), subungual hyperkeratosis (133/297, 44.78%), oil drop sign (126/297, 42.42%), complete onycholysis (121/297, 40.74%), linear margin of the proximal onycholysis (107/297, 36.03%) and linear erythema at the margin of the onycholysis (77/297, 25.93%). Compared with the patients with fingernail psoriasis, those with toenail psoriasis more commonly presented with subungual hyperkeratosis (81[58.27%] vs. 52[32.91%], P < 0.001), punctate/blocky haemorrhages (22[15.83%] vs. 11[6.96%], P < 0.05), longitudinal striae (34[24.46%] vs. 10[6.33%], P < 0.001), longitudinal nail splitting (24[17.27%] vs. 9[5.70%], P < 0.01), brown discoloration (14[10.07%] vs. 2[1.27%], P < 0.01), transverse grooves (17[12.23%] vs. 1[0.63%], P < 0.001) and leukonychia (10[7.19%] vs. 1[0.63%], P < 0.01) ; compared with the patients with toenail psoriasis, those with fingernail psoriasis more commonly presented with splinter haemorrhages (100[63.29%] vs. 64[46.04%], P < 0.01), oil drop sign (81[51.27%] vs. 45[32.37%], P < 0.01), linear erythema at the margin of the onycholysis (55[34.81%] vs. 22[15.83%], P < 0.001), partial onycholysis (50[31.65%] vs. 19[13.67%], P < 0.001) and red spots in the lunula (36[22.78%] vs. 12[8.63%], P < 0.01) . Conclusion:The dermoscopic features of toenail psoriasis were quite different from those of fingernail psoriasis, and features such as subungual hyperkeratosis, longitudinal streaks, and brown discoloration were more commonly presented in patients with toenail psoriasis.