Poloxamer， as a non-ionic surfactant， exhibits a unique triblock [polyethylene oxide-poly （propylene oxide）-polyethylene oxide] structure， which endows it with broad application potential in various fields， including solid dispersion technology， nanotechnology， gel technology， biologics， gene engineering and 3D printing. As a carrier， it enhances the solubility and bioavailability of poorly soluble drugs. In the field of nanotechnology， it serves as a stabilizer etc.， enriching preparation methods. In gel technology， its self-assembly behavior and thermosensitive properties facilitate controlled drug release. In biologics， it improves targeting efficiency and reduces side effects. In gene engineering， it enhances delivery efficiency and expression levels. In 3D printing， it provides novel strategies for precise drug release control and the production of high-quality biological products. As a versatile material， poloxamer holds promising prospects in the pharmaceutical field.

ObjectiveTo investigate the effect of 1，25（OH）₂D₃ on the level of peroxisome proliferator-activated receptor-γ （PPAR-γ） in the liver， the phenotype of hepatic macrophages， and liver inflammation in a rat model of nonalcoholic steatohepatitis （NASH）， as well as the mechanism of 1，25（OH）₂D₃ improving liver inflammation. MethodsAfter 1 week of adaptive feeding， 24 specific pathogen-free Wistar rats were randomly divided into normal group ［choline-supplemented L-amino acid-defined （CSAA） diet］， normal+1，25（OH）₂D₃ group ［CSAA diet+1，25（OH）₂D₃］， model group ［choline-deficient L-amino acid-defined diet （CDAA） diet］， and model+1，25（OH）₂D₃ group ［CDAA diet+1，25（OH）₂D₃］， with 6 rats in each group. The dose of 1，25（OH）₂D₃ was 5 μg/kg for intraperitoneal injection twice a week for 12 weeks. The serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） were measured， liver histopathology was observed， and SAF score was assessed. M1 hepatic macrophages and M2 hepatic macrophages were measured to analyze in the change in the phenotype of hepatic macrophages， and ELISA was used to measure the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in liver tissue， and qPCR was used to measure the mRNA level of PPAR-γ. The two-factor analysis of variance was use for comparison between groups， and the least significant difference t-test was used for further comparison； the Pearson method was used for correlation analysis. ResultsCompared with the normal group， the model rats with CDAA diet-induced NASH had significant increases in the serum levels of AST and ALT （P=0.019 and P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P<0.001）， as well as a significant increase in the level of TNF-α （P<0.001） and a significant reduction in the level of IL-4 in liver tissue （P=0.025）. The 1，25（OH）₂D₃ group had significant reductions in the serum levels of ALT （P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P=0.001）， the level of IL-1β （P<0.001） and a significant increase in the level of M2 hepatic macrophages （P=0.017）， the level of IL-10 （P=0.039）， the level of IL-4 （P<0.001）， the level of PPAR-γ （P=0.016）. There were significant interactions between CDAA diet-induced NASH model and 1，25（OH）₂D₃ in serum the levels of AST and ALT （P=0.007 and P=0.008）， the SAF scores of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， the level of M2 hepatic macrophages （P=0.008）， the ratio of M1 and M2 of hepatic macrophages （P=0.005）， the level of TNF-α （P<0.001）， the level of IL-10 （P=0.038）， the level of IL-4 （P<0.001） and the level of PPAR-γ （P=0.009）. The correlation analysis showed that PPAR-γ was negatively correlated with the ratio of M1 and M2 hepatic macrophages （r=-0.415， P=0.044） and was positively correlated with M2 hepatic macrophages （r=0.435， P=0.033）， IL-10 （r=0.433， P=0.035）， and IL-4 （r=0.532， P=0.007）. ConclusionThis study shows that 1，25（OH）₂D₃ improves liver inflammation in NASH by activating PPAR-γ to regulate the phenotypic transformation of hepatic macrophages.

ObjectiveTo characterize the evidence distribution and methodological quality of randomized controlled trials （RCTs） on oral Chinese herbal medicine （CHM） for atopic dermatitis （AD） based on evidence mapping. MethodsSeven databases （CNKI， Wanfang Data， VIP， CBM， Cochrane Library， PubMed， and Embase） and the Chinese Clinical Trial Registry were searched for the RCTs in Chinese and English. Evidence distribution was presented graphically and textually， and methodological quality was assessed via the Cochrane Risk of Bias tool （ROB 1.0）. ResultsA total of 168 RCTs were included. The number of annual publications showing an increasing trend， and 72.6% RCTs had sample sizes of 51-100 participants. The studies evaluated 108 distinct CHM interventions categorized as decoctions， granules， Chinese patent medicines， and extracts. Compound Glycyrrhizin was the most frequently used， followed by Xiaofengsan and Chushi Weiling decoction. Among the RCTs， 57.1% had the treatment courses of 4-8 weeks. Outcome measures predominantly focused on clinical response rate， skin lesion severity scores， and adverse events， with less attention to TCM symptom scores， skin barrier function， and relapse rates. The overall risk of bias was generally high. ConclusionWhile CHM for AD is a research hotspot and demonstrates clinical advantages， the related studies have problems such as unclear clinical positioning， poor research standardization and methodological quality， and insufficient prominence of TCM clinical advantages. Large-sample， methodologically rigorous， and high-quality studies are needed to enhance the evidence base for CHM in treating AD.

ObjectiveTo characterize the evidence distribution and methodological quality of randomized controlled trials （RCTs） on oral Chinese herbal medicine （CHM） for atopic dermatitis （AD） based on evidence mapping. MethodsSeven databases （CNKI， Wanfang Data， VIP， CBM， Cochrane Library， PubMed， and Embase） and the Chinese Clinical Trial Registry were searched for the RCTs in Chinese and English. Evidence distribution was presented graphically and textually， and methodological quality was assessed via the Cochrane Risk of Bias tool （ROB 1.0）. ResultsA total of 168 RCTs were included. The number of annual publications showing an increasing trend， and 72.6% RCTs had sample sizes of 51-100 participants. The studies evaluated 108 distinct CHM interventions categorized as decoctions， granules， Chinese patent medicines， and extracts. Compound Glycyrrhizin was the most frequently used， followed by Xiaofengsan and Chushi Weiling decoction. Among the RCTs， 57.1% had the treatment courses of 4-8 weeks. Outcome measures predominantly focused on clinical response rate， skin lesion severity scores， and adverse events， with less attention to TCM symptom scores， skin barrier function， and relapse rates. The overall risk of bias was generally high. ConclusionWhile CHM for AD is a research hotspot and demonstrates clinical advantages， the related studies have problems such as unclear clinical positioning， poor research standardization and methodological quality， and insufficient prominence of TCM clinical advantages. Large-sample， methodologically rigorous， and high-quality studies are needed to enhance the evidence base for CHM in treating AD.

Objective The aim of this study was to demonstrate a novel jaw position adjustment technique derived from digital twins and evaluate the application ef-fect of digital technology-assisted optimization in the pro-cess of adjusting jaw position on patients with temporo-mandibular disorders(TMD).Methods A total of 74 patients with TMD who attended the Department of Temporomandibular Joint,West China Hospital of Stomatology,Si-chuan University,between June 2022 and May 2023 were selected.The patient's initial computed tomography(CT)and bilateral temporomandibular joint data obtained by magnetic resonance imaging(MRI)were collected.The 148 joints were divided into the normal disc-condyle relationship(N)group,disc displacement with reduction(DDWR)group,and disc displacement without reduction(DDWoR)group.Assisted by digital technology,the patient's CT data were recon-structed,and a personalized reference plane was established to adjust the jaw position.A three-point bite guiding splint was designed by the adjusted occlusal space and then fabricated by 3D printing technology.It was worn by the patients and then reviewed by MRI.Before and after the adjustment of jaw position,the amount and direction of condyle and disc displacement and the angle between condyle and disc were measured as the evaluation indexes of the effect of the adjust-ment.The correlation with condylar displacement was evaluated.Results In the N group,the disc moved backward and downward along the X and Z axes by(-0.60±0.62)and(0.51±0.71)mm,respectively.In the DDWR group,the disc moved backward and upward along the X and Z axes by(-1.33±1.38)and(-0.09±1.31)mm,respectively.In the DDWoR group,the disc moved forward and downward along the X and Z axes by(0.49±1.76)and(1.35±1.76)mm,re-spectively.The angle between the condyle and the disc decreased after adjustment of the jaw position in all three groups.All patients showed improvement in symptoms after adjustment.Conclusion Digital technology-assisted jaw position adjustment can simplify the process,reduce the sensitivity of the technique,and improve patients'disc-condyle structure and symptoms.Therefore,its application in the treatment of patients with TMD is of great clinical significance.

Objective:To investigate the clinical efficacy of modified Ligustrum lucidum and oyster decoction combined with tomoxetine hydrochloride in the treatment of attention deficit hyperactivity disorder in children.Methods:A total of 152 children with attention deficit hyperactivity disorder who were treated at Jinhua Maternal & Child Health Care Hospital from February 2020 to June 2022 were included in this study. Using a prospective study approach, the patients were divided into two groups based on the propensity score matching method: 76 patients in the control group and 76 patients in the observation group. The control group was treated with tomoxetine hydrochloride, while the observation group received modified Ligustrum lucidum and oyster decoction combined with tomoxetine hydrochloride. Clinical treatment effects on the children were evaluated using the Swanson, Nolan, and Pelham Rating Scale-version Ⅳ (SNAP-Ⅳ). Six months after treatment, the clinical efficacy of both groups was observed and compared. In addition, changes in relevant indicators from before treatment to 6 months post-treatment were compared.Results:At 2 months of treatment, the SNAP-Ⅳ scores for the control and observation groups were (24.21 ± 4.19) points and (20.75 ± 4.74) points, respectively, which were significantly lower than those measured at 1 month of treatment [(32.45 ± 3.23) points, (31.56 ± 4.90) points, t = 13.57, 13.82, both P < 0.05]. At 3 months of treatment, the SNAP-Ⅳ scores for the control and observation groups were (20.56 ± 3.03) points and (17.28 ± 3.06) points, respectively, which were significantly lower than those measured at 1 and 2 months of treatment ( t = 23.40, 21.54, 6.15, 5.36, all P < 0.05). At 6 months of treatment, the SNAP-Ⅳ scores for the control and observation groups were (18.34 ± 4.28) points and (13.87 ± 2.89) points, respectively, which were significantly lower than those measured at 1, 2 and 3 months of treatment ( t = 22.94, 27.10, 8.54, 10.80, 3.69, 7.06, all P < 0.05). At 2, 3, and 6 months of treatment, the SNAP-Ⅳ scores for the observation group were significantly lower than those in the control group at the respective time points ( t = 4.76, 6.64, 7.54, all P < 0.001). The total response rate in the observation group was 81.58% (62/76), which was significantly higher than that in the control group [60.53% (46/76), χ2 = 8.18, P < 0.05]. There was no significance in incidence of adverse reactions between the observation and control groups [5.26% (4/76) vs. 9.21% (7/76), P > 0.05]. Conclusion:Modified Ligustrum lucidum and oyster decoction, when combined with atomoxetine hydrochloride, exhibits better efficacy in the treatment of attention deficit hyperactivity disorder in children compared with atomoxetine hydrochloride alone. The combined therapy has no obvious adverse reactions.

Objective To construct a recombinant poxvirus vector vaccine, rVTTδTK-RBD, and to evaluate its safety and immunogenicity. Methods The receptor-binding domain (RBD) gene was synthesized with reference to the gene sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was inserted into the polyclonal site of the self-constructed recombinant plasmid pSTKE, to construct the recombinant poxvirus shuttle vector pSTKE-RBD. This was then transfected into BHK-21 cells pre-infected with the vaccinia virus Tiantan strain (VTT). The recombinant poxvirus rVTTδTK-RBD was successfully obtained after several rounds of fluorescence phage screening. The effect of rVTTδTK-RBD on the body mass of BALB/c mice was detected after immunizing mice by intra-nasal vaccination. The levels of specific and neutralizing antibodies produced by rVTTδTK-RBD on BALB/c mice were analyzed after immunizing mice intramuscularly. The effect of rVTTδTK-RBD on T cell subsets in BALB/c mice was detected by flow cytometry. Results Through homologous recombination, enhanced green fluorescent protein (EGFP) screening marker, and multiple rounds of fluorescent phosphorescence phage screening, a recombinant poxvirus rVTTδTK-RBD, expressing RBD with deletions in the thymidine kinase (TK) gene, was successfully obtained, which was validated by PCR. The in vivo experiments on BALB/c mice showed that rVTTδTK-RBD was highly immunogenic against SARS-CoV-2 and significantly reduced toxicity to the body compared to the parental strain VTT. Conclusion The recombinant poxvirus vaccine rVTTδTK-RBD against SARS-CoV-2 is successfully constructed and obtained, with its safety and immunogenicity confirmed through various experiments.
Animals ; Mice ; SARS-CoV-2/genetics* ; COVID-19 ; Vaccines, Synthetic/genetics* ; Genes, Reporter ; Bacteriophages ; Mice, Inbred BALB C

Objective To preliminarily verify the effectiveness and safety of bloodletting combined with drug bamboo cups in intervention of degenerative lumbar spinal stenosis,and to explore the prognostic factors that affect the efficacy of TCM regimens in the treatment of DLSS.Methods 64 consecutive patients with degenerative lumbar spinal stenosis were enrolled.Bloodletting combined with drug bamboo cup intervention was used.Acupoints were selected and treated with the same length of the governor channel of the lumbar spine,the first and second side lines of the bladder meridian and Ashi point,weekly 2 times,8 times per course,2 consecutive courses of treatment.Before treatment,after treatment,and 1 month follow-up,the changes of the patient's lumbar spinal stenosis specific scale(SSM),modified Oswestry dysfunction index(ODI),and 12 health survey summary scores(SF-12)were observed.Using SSM symptom or function score≥0.5,the criteria for grouping were first single-factor analysis,and then logistic regression was used to analyze the prognostic factors of the treatment.Results After 2 courses of treatment,the patient's SSM symptom score(2.25±0.56),SSM function score(2.06±0.67),ODI index(15.49±8.72),and SF-12 physiological score(36.31±7.35)were more significant than before treatment Improved,the difference was statistically significant(P<0.05),the SF-12 psychological score(49.70±9.47),the difference was not statistically significant compared with before treatment(P>0.05);the patient's SSM symptom score(2.22±0.54)was followed up for one month,SSM function score(2.09±0.66),ODI index(15.53±8.23),SF-12 physiological score(36.55±7.25),SF-12 psychological score(50.62±9.17),which are significantly better than before treatment,and the difference is statistically significant(P<0.05),the difference was not statistically significant(P>0.05)after 2 courses of treatment.The univariate logistic regression analysis of each influencing factor showed that:BMI,baseline symptom dimension,baseline functional dimension,foraminal stenosis,lateral recess stenosis,and two-stage stenosis had statistically significant differences between the effective and ineffective groups(P<0.05).Conclusion Bloodletting combined with drug bamboo cups has a certain clinical effect on degenerative lumbar spinal stenosis.

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.