Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective To investigate the morphological typing and clinical significance of the distal tibiofibular syndesmosis fibular notch based on CT images. Methods According to the inclusion and exclusion ceiteria‚ the imaging data of patients undergoing ankle joint CT examination were analyzed‚ and the inferior tibiofibular joint fibula notch was classified according to the morphological characteristics. The measurements included 8 distances. There were 123 males and 102 females‚ all of whom were Han nationality‚ aged 18-60 years old. Results Retrospectively analyzed the result of 225 patients from December 2013 to December 2022. The distal tibiofibular syndesmosis fibular notch was divided into four types according to morphological characteristics‚ C-shaped (50. 67%)‚ V-shaped (26. 67%)‚ flat-shaped (15. 11%) and L-shaped (7. 56%). The angle between the anterior and posterior facets of the flat shape (145. 56 ± 9. 25)° was the largest and the angle between the anterior and posterior facets of the L shape (125. 07 ± 13. 54)° was the smallest(P< 0. 05); the depth of the notch in the flat shape (3. 11 ± 0. 83) mm was the smallest and in the L shape (4. 47±1. 11) mm was the largest(P<0. 05);The posterior facet length (13. 06 ± 3. 56) mm and anterior tibiofibular gap (3. 83±1. 49) mm on left were larger than on the right side (P<0. 05); The posterior facet length (13. 36 ± 3. 46) mm‚ fibular notch depth (3. 93 ± 1. 10) mm and vertical distance of tibiofibular overlap (9. 10 ± 2. 55) mm larger in men than in women (P<0. 05). Conclusion In this study‚ the data related to the inferior tibiofibular syndesmosis notch were measured and divided into four types according to the shape. The flat inferior tibiofibular syndesmosis notch is more likely to have chronic ankle instability‚ and the fibula is more likely to move forward during anatomical reduction. The inferior tibiofibular syndesmosis of L-shaped and C-shaped notches is more prone to posterior displacement of fibula or poor rotation reduction during anatomical reduction.

Objective: To explore the intervention effect of 12 week spinal health exercise on adolescents high and low shoulders, in order to provide empirical evidence for exploring simple and feasible measures to intervene. Methods: In February 2023, 60 high and low shoulder students from a vocational high school in a certain county of Luzhou City were randomly selected as the research subjects by convenient sampling method. Paired sampling was used to randomly divide participants into an intervention group and a control group with 30 students each group. The intervention group received spinal health gymnastics intervention during 12 weeks of morning exercises and large break exercises for twice a day, with two groups each time; the control group maintained their previous morning exercises and large break exercises. A follow up study was conducted on the height difference between the left and right shoulder peaks of the intervention group and the control group students before intervention, after 12 weeks intervention, at 4 weeks post intervention. The t-test was used to analyze the changes in shoulder peak height difference between the intervention group and the control group. Results: Before intervention, there was no statistically significant difference in the height of the left and right shoulder peaks between the intervention group [(2.50±1.19)cm] and the control group [(2.49±1.20)cm] adolescents ( t=0.05, P > 0.05). After 12 weeks of intervention, the difference in shoulder height between the left and right sides of adolescents in the intervention group decreased, compared to that before intervention [(1.43±1.15, 2.50±1.19)cm], while the control group increased compared to that before intervention [(2.58±1.19, 2.49±1.20) cm], and the differences were both statistically significant ( t= -78.17 , 20.15, P <0.05). At 4 weeks post intervention, there was no statistically significant difference in the height of the left and right shoulder peaks between the intervention group [(1.44±1.15)cm] and the control group [(2.59±1.18)cm] compared to 12 weeks after the intervention ( t=1.80, 1.05, P >0.05). The intervention group [(2.49±1.26, 2.52±1.16) (1.43±1.21, 1.44±1.13) (1.44±1.21, 1.45±1.14)cm] and the control group [(2.45±1.24, 2.52±1.20) (2.55±1.24, 2.61±1.18) (2.55±1.22, 2.62±1.18)cm] showed no statistically significant difference in the height of the left and right shoulder peaks between males and females before intervention, after 12 weeks of intervention, and after stopping intervention for 4 weeks ( t =-0.08, -0.03, -0.02; -0.15, -0.12, -0.15, P >0.05). Conclusions Spinal health gymnastics has a good effect on correcting high and low shoulders in adolescents. Spinal health gymnastics should be promoted on campus to promote adolescent posture health.

Cognitive dysfunction is the impairment of higher brain functions.Cognitive impairment caused by neuropsychiatric diseases has caused serious impact on patients'quality of life and the outcome of the disease.The transcranial alternating current stimulation(tACS)improves cognitive function by modulating neural oscillations of specific frequencies,affecting the release of neurotransmitters such as serotonin and dopamine,and enhancing local and distal synchronization of brain networks.Specific frequencies of tACS can improve the cognitive impairment caused by Alzheimer disease(AD),schizophrenia,and depression,among which the gamma and theta frequencies of tACS have the most significant effects on cognitive function.tACS has high safety and low operational difficulty,and has great potential to improve cognitive function.

Objective To investigate the effects of emodin on the healing of infected wound and the regulation of Toll-likereceptor 4(TLR4)/nuclear factor kappa-B(NF-κB)signaling pathway in rats.Methods The model of infectious wounds rats were constructed by the full-thickness skin defect method.The successful model rats were randomly divided into model group,control group and experimental-L,-M,-H groups with 12 rats per group;another 12 normal rats were taken as the normal group.Experimental-L,-M,-H groups was applied with emodin 150,300 and 600 μg·d-1 and 200 mg·kg-1 emodin by gavage,respectively.Control group was applied with mopirolacin cream 0.1 g·d-1 on rat wounds,once a day.Normal and model groups were treated with 0.9％NaCl.Six groups were treated for 21 days.The wound healing rates and dynamic blood flow were measured.The levels of tumor necrosis factor(TNF)-α and interleukin(IL)-1β in serum and the hydroxyproline(HYP)and catalase(CAT)in wound tissue were measured by enzyme linked immunosorbent assay.The protein levels of TLR4 and NF-κB in wound were determined by Western blot.Results The wound healing rates of experimental-M,-H groups,control group and model group were(50.70±1.26)％,(75.51±0.50)％,(69.44±1.65)％and(28.58±5.09)％,respectively.The dynamic blood flow values of experimental-M,-H groups,control group,model group and blank group were(123.71±3.71),(155.61±2.47),(146.29±2.04),(79.47±4.76)and(158.00±1.93)mL·min-1;the levels of TNF-α were(81.05±2.32),(56.69±1.59),(69.53±2.39),(139.46±2.46)and(46.49±5.71)ng·L-1;the levels of IL-1β were(59.87±0.83),(42.66±1.30),(48.37±3.34),(88.79±1.84)and(33.93±2.19)ng·L-1;the levels of HYP were(24.79±0.82),(31.12±1.16),(25.83±1.12),(16.88±2.20)and(32.95±1.18)pg·mg-1;the levels of CAT were(24.99±1.47),(34.52±1.26),(31.00±1.15),(13.70±2.09)and(34.23±0.70)U·mg-1;the relative expression levels of TLR4 protein were 0.74±0.05,0.53±0.05,0.55±0.04,1.09±0.07 and 0.23±0.05;the relative expression levels of NF-κB protein were 0.69±0.06,0.44±0.04,0.52±0.03,1.10±0.04 and 0.22±0.10,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups were statistically significant(all P＜0.05).Conclusion Emodin can improve the infectious wound healing and dynamic blood flow in rats,and inhibit the inflammatory levels and oxidative stress response in wound tissue,and the mechanism may be related to the regulation of TLR4/NF-κB pathway.

Objective To observe the effect of Ginkgo biloba extract(GBE)on depression like behavior in post stroke depression(PSD)model rats,and explore the mechanism of regulating Toll like receptor 4/nuclear factor-κ B(TLR4/NF-κB)pathway to inhibit neuroinflammation.Methods Rats were randomly divided into 6 groups,sham,cerebral ischemia,PSD,paroxetine,low-dose Ginkgo biloba extract(GBE-L)and high-dose Ginkgo biloba extract(GBE-H)groups,10 rats in each group.Except for the sham group,middle cerebral artery occlusion(MCAO)was performed to prepare a left focal cerebral ischemia model.Except for the sham group and cerebral ischemia group,other groups were subjected to chronic unpredictable mild stress(CUMS)to establish PSD rat model for 8 weeks.After 4 weeks of CUMS,the paroxetine group,GBE-L,and GBE-H were treated with paroxetine 5 mg·kg-1,GBE 50 mg·kg-1,and GBE 100 mg·kg-1,respectively.The sham group,cerebral ischemia group,and PSD group were treated with the same volume of 0.9％NaCl and continuously administered by gavage for 28 d.After 4 weeks and 8 weeks of CUMS,the body weight and sugar preference test were measured.Levels of serum tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β)and levels of norepinephrine(NE),serotonin(5-HT),and dopamine(DA)in the cerebral cortex were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of Tlr4,Nfkb1,and nuclear factor κ B-kinase subunit β inhibitory factor(Ikbkb)in the hippocampus of rats were detected by polymerase chain reaction.The protein levels of NF-κB,nuclear factor κB inhibitory protein α(IKBα)and phosphorylation nuclear factor κB inhibitory protein α(p-IKB)in hippocampal tissue were detected by Western blot.Results The body weights of rats in the sham group,cerebral ischemia group,PSD group,paroxetine group,GBE-L group and GBE-H group were(427.10±6.36),(403.10±7.37),(310.10±9.71),(355.00±4.03),(347.90±9.88)and(391.90±5.07)g;sugar preference rate were(93.93±1.78)％,(91.57±1.03)％,(54.72±7.34)％,(88.35±4.36)％,(63.55±12.73)％and(81.04±4.31)％;the levels of NE in the cerebral cortex were(1 951.14±52.86),(1 827.27±23.63),(1 662.12±35.92),(2 033.58±72.28),(1 887.31±33.07)and(2 175.00±42.54)pg·mL-1;the levels of 5-HT in the cerebral cortex were(237.07±8.86),(226.15±10.27),(214.51±3.46),(297.13±5.79),(274.14±7.63)and(285.34±8.72)ng·mL-1;the levels of DA in the cerebral cortex were(1 531.11±47.26),(1 209.89±58.09),(1 143.15±36.31),(1 812.67±51.28),(1 651.56±31.82)and(1 853.33±20.42)pg·mL-1.Compared with the PSD group,GBE significantly increased the body weight of rats(P＜0.01)and increased the preference rate of sugar water in rats,showing the antidepressant like behavioral.GBE significantly reduced the levels of serum TNF-α,IL-1 β(all P＜0.01),increased the levels of NE,5-HT,and DA in the cerebral cortex(all P＜0.01),down regulate the mRNA levels of Tlr4,Nfkb1 and Ikbkb(P＜0.05,P＜0.01),reduced the expression of NF-κB(P＜0.01),and reduced the phosphorylation of IKBα(P＜0.01).Conclusion Ginkgo biloba extract can improve depression-like behavior in PSD model rats,and has antidepressant effect.Its mechanism is related to the inhibition of TLR4/NF-κB pathway,thus reducing neuroinflammation.

Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.

Orodispersible films (oral dispersible films), a novel form of oral solid dosage forms, are widely used for patients with dysphagia and those with uncontrollable autonomic behavior. In this study, suvorexant orodispersible film was prepared by hot melt extrusion technology, and the disintegration time, mechanical properties, in vitro dissolution and pharmacokinetics were evaluated, compared with other orodispersible films and commercially available tablets Belsomra. All experiments were approved by the Committee on the Management and Use of Laboratory Animals of Academy of Military Medical Sciences (IACUC-DWZX-2024-504). The results showed that the dissolution rate of suvorexant orodispersible film was faster and the mechanical strength was better than that of other commercially available orodispersible film, which could meet the needs of storage and transportation. Differential scanning calorimetry and X-ray diffraction results showed that suvorexant was dispersed within the orodispersible film in an amorphous state. The in vitro dissolution of the film was observed to be four times faster than that of the commercial tablets, achieving complete dissolution within five minutes. Pharmacokinetic evaluations in Beagle dogs revealed that the self-formulated orodispersible film exhibited no significant differences in the area under the blood concentration-time curve when compared with Belsomra. However, the film showed a faster onset of action, with a peak time that was twice as rapid, and a maximum blood concentration that was twice as high as that of Belsomra. Leveraging hot melt extrusion technology, the suvorexant orodispersible film offers a straightforward, continuous production process with consistent quality. It serves as an excellent platform for the development of solvent-free film preparations tailored for patients with special needs.

The rheological properties of drug and carrier materials have a wide range of guiding significance for the formulation and process development of solid dispersions. In this study, the rheological properties of materials with different drug carrier ratios were systematically studied with suvorexant as the model drug and copovidone as the carrier material, which provided a sufficient basis for determining the formulation and process of solid dispersions. The optimal suvorexant-copovidone ratio obtained by oscillating temperature scanning was 1∶4. If the ratio is greater than 1∶ 4, the glass transformation temperature of the material will increase significantly, and the solubilization effect of the solid dispersion will show a downward trend. The results of oscillation temperature scanning and oscillation temperature sweep can show that when the extrusion temperature is greater than 150 ℃, the viscosity of the material is less than 10 000 Pa·s, and the melt can be extruded smoothly, and the best extrusion temperature of 160-180 ℃ can be obtained by combining the dissolution results. Finally, the dissolution of suvorexant tablets guided by rheological property studies in multiple media is similar to that of the commercially available tablets Belsomra. Therefore, rheological studies can screen and optimize the formulation and process of suvorexant solid dispersions at the mechanism level, which is of great significance to improve the success rate of R&D and shorten the R&D cycle of solid dispersions prepared by hot melt extrusion.