Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT₇ receptor protein expression in the cells, indicating potential antidepressant activity.

Objective Evaluation of the effect and mechanism research of Qi-Shen-Yi-Zhi formula on improving learning and memory ability in mice injected with Aβ1-42 in hippocampus.Methods Alzheimer's disease model mice were constructed by injecting β amyloid peptide 1-42 into hippocampus and treated with water extracts of Qi-Shen-Yi-Zhi formula.The cognitive abilities of mice were assessed using Morris water maze and Y maze tests,which measure learning and memory capabilities.HE staining was used to observe the damage and TUNEL method was used to determine apoptosis of hippocampus.Detection of the expression of oxidative factors,inflammatory factors,and related antioxidant proteins and apoptotic proteins in the hippocampal tissue of a mouse model of dementia.Results Both high-dose and low-dose groups of Qi-Shen-Yi-Zhi formula significantly improved cognitive dysfunction in mice injected with Aβ1-42 in hippocampus,and attenuated the damage and apoptosis of the hippocampus.It also inhibited oxidative stress and downregulated the expressions of inflammatory factors IL-6,IL-1β and TNF-a,increased the expression of antioxidant proteins Nrf2 and HO-1,and regulated the expressions of apoptotic proteins Caspase-9,Caspase-3,Bax and Bcl-2.Conclusion Qi-Shen-Yi-Zhi formula improves the learning and memory abilities of mice injected with Aβ1-42 in hippocampus,which might be related to the attenuation of oxidative stress and neuronal inflammation of hippocampus.

Objective To study the effective fraction and mechanism of Lycium barbarum leaves on improving learning and memory ability of subacute aging mice induced by D-galactose injection.Methods The model of subacute aging mice was developed by injection of D-galactose subcutaneously,and different extracts of Lycium barbarum leaves were prepared.The effects of the extracts of Lycium barbarum leaves on the learning and memory ability of model mice were evaluated by Y maze experiment and new object recognition experiment.The pathomorphological changes of hippocampus in mice were observed by hematoxylin-eosin and Nissl staining.The levels of brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),glial cell line-derived neurotrophic factor(GDNF),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)and interleukin-10(IL-10)in hippocampus of mice were detected by enzyme-linked immunosorbent assay.The activities of superoxide dismutase(SOD)and the contents of glutathione(GSH)and malondialdehyde(MDA)in hippocampus of mice were detected by related assay kits.Detection of apoptosis in the hippocampal region of mouse brain tissue using the TUNEL method.Western blotting analysis was used to detect the expressions of antioxidant proteins Nrf2,HO-1 and apoptotic proteins Caspase-3,Caspase-9 in hippocampus of mice.Results The water extraction part and 80%alcohol precipitation supernatant part of Lycium barbarum leaves significantly improved the learning and memory ability of model mice,improved the pathological damage of hippocampus in mice,increased the number of Nissl bodies in hippocampus of mice,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF.Pro-inflammatory factors TNF-α,IL-1β and IFN-γ expression declines while anti-inflammatory factor IL-10 expression rises.The activity of SOD and the expression of GSH were increased,and the expression of MDA was decreased.Increase the expression of Nrf2 and HO-1 antioxidant proteins;reduce the expression of Caspase-3 and Caspase-9 apoptosis pathway proteins.Inhibition of apoptosis in the hippocampal region of mouse brain tissue using a model.Conclusion The water extracts and 80%alcohol precipitation supernatant extracts of Lycium barbarum leaves are the effective fractions of Lycium barbarum leaves to improve the learning and memory ability of D-galactose-induced subacute aging mice,and its mechanism might be related to the inhibition of neuronal apoptosis caused by oxidative stress and inflammation.

Ritlecitinib is an inhibitor that acts on Janus kinase 3 and the hepatocellular carcinoma kinase family.In June 2023,the FDA approved Ritlecitinib for the treatment of severe alopecia areata in patients aged 12 years and above.Multiple clinical studies have observed hair regeneration in patients after using Ritlecitinib,which is generally safe and well tolerated during use.This article introduces its pharmacological effects,pharmacokinetics,clinical research,safety,and usage and dosage.

OBJECTIVE To evaluate the effect of Qishen Yizhi formula on improving learning and memory ability in D-galactose subcutaneous injection induced subacute aging mice.METHODS Subacute aging mice model mice were developed by D-galactose subcutaneous injection and then treated with positive drug donepezil(2 mg·kg-1·d-1)and Qishen Yizhi formula water extracts in low(1.33 g·kg-1·d-1)and high dose group(2.67 g·kg-1·d-1).The learning and memory abilities of mice were evaluated using Morris water maze and Y maze tests;HE staining was used to examine hippocampal damage in model mice;TUNEL was used to detect apoptosis of mouse hippocampal tissue;ELISA was used to detect the expression levels of oxidative stress factors and inflammatory fac-tors in the mouse hippocampus tissue;Western blot was used to detect the expression of signaling pathway proteins related to apoptosis,oxidative stress and inflammatory stress in the hippocampus of mice.RESULTS The water extract of Qishen Yizhi formula signifi-cantly shortened the latency and distance of model mice for reaching the platform in the water maze test(P<0.01),and significantly increased the number of crossing the platform(P<0.01);increased the exploration time and number of the Y maze new arm in model mice(P<0.05);inhibited the TUNEL fluorescence expression in the hippocampus of model mice(P<0.01);upregulated the activity of the oxidative stress factor superoxide dismutase(SOD)(P<0.05)and glutathione(GSH)content(P<0.05),and downregulated malondialdehyde(MDA)content(P<0.05);reduced interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF-α)expression levels(P<0.05,P<0.01);decreased the expression of apoptosis signaling pathway proteins Cleaved Caspase-3 and Caspase-3(P<0.05),upregulated the expression of oxidative stress signaling pathway proteins Nrf2 and HO-1(P<0.05),and downregulated the expression of inflammatory stress signaling pathway proteins p-NF-κB and NF-κB(P<0.05).CONCLUSION Qishen Yizhi for-mula can improve the learning and memory ability of subacute aging model mice injected with D-galactose,which may be related to its inhibitory effect on hippocampal oxidative stress and inflammatory stress.

Objective:To evaluate the effect of polyetheretherketone (PEEK) periodontal splints and splints made from other materials under static loading on stress distributions in periodontal tissues, cement layer, and splints themselves.Methods:A finite element model based on cone-beam CT imaging data of a 25-year-old male patient (treated at the Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University in October 2021 for a cracked maxillary molar) with a healthy and intact mandibular dentition and periodontal health was constructed. The finite element model included anterior mandible dentition, mandibular bone model without bone resorption (WBR group), a periodontally compromised mandible model (control group), and three types of periodontal splints: a PEEK periodontal splint (0.7 mm thick, Young′s modulus: 4.1 MPa), a fiber-reinforced resin (FRC) splint (1.0 mm thick, Young′s modulus: 37.0 MPa), and a titanium splint (1.2 mm thick, Young′s modulus: 110.0 MPa). The bone resorption models fixed with different periodontal splints constituted the experimental groups (PEEK group, FRC group and titanium group). Loading of 100 N was applied on the midpoint of the incisal edge of tooth 41. The direction was set at 0°, which was parallel to the long axis of the tooth and downward. The buccal to lingual and downward angles were 30°and 60°, respectively, perpendicular to the long axis of the tooth and 90° to the lingual side. The finite element analysis software was utilized to analyze the stress distribution characteristics of the periodontal tissues, adhesive layer, and the splint itself in the anterior mandibular teeth among the different group.Results:Under the different loading simulation, in the control group, the maximal von Mises stresses of periodontal ligament and bone were 15.7-50.2 MPa and 38.8-130.3 MPa, respectively, and in the WBR group, the maximal von Mises stresses of periodontal ligament and bone were 3.6-6.4 MPa and 16.5-42.7 MPa, respectively. Under the same loading conditions, the magnitude of maximal von Mises stresses in periodontal tissues in the PEEK group was 4.6-6.2 MPa, and the magnitude of stresses in the periodontal ligament of 41 teeth in the WBR group was similar to that in the PEEK group, but higher than that in the FRC and titanium groups. The maximal von Mises stresses of each group is primarily distributed in the periodontal ligament and alveolar bone at the cervical area of the tooth. The higher the elastic modulus of the splint, the higher its own maximal von Mises stresses, and the smaller the maximal principal stresses transmitted to the adhesive layer. In the PEEK group and titanium group, the stress distribution area in the adhesive layer and the splint was near the splint connection adjacent to tooth 41.Conclusions:Periodontal splints fabricated from three types of materials, are effective in distributing stress within the periodontal tissues of the abutment teeth. Compared to FRC and titanium group, the higher PEEK splint stress value was obtained, and the smaller the stress value was transmitted to its adhesive layer.

Cognitive dysfunction refers to dysfunction of individual perception,memory,understanding,learning,creation and other dysfunctions caused by abnormal brain function and structure.Based on the fact that the spleen can't regulate transportation and transformation,govern blood and send up essential substance,combined with the microbiota-gut-brain axis,this article discussed the etiology and pathogenesis of intestinal flora imbalance affecting cognitive dysfunction in TCM.It was proposed that the spleen in TCM and intestinal flora are connected in physiology and pathology:the spleen regulates spirit and governs cognition,when the spleen fails to function normally that it can't dominate transportation and transformation,govern blood and send up essential substance will cause that the brain spirit can not be nourished;intestinal flora is closely related to the spleen in TCM,and affects brain function through the nervous system,endocrine,immune and metabolic mechanisms.This article can provide explore new ideas for the clinical research and treatment of cognitive dysfunction of traditional Chinese and Western medicine.

Immune Checkpoint Inhibitors ; Transcriptome ; Immunotherapy ; Biomarkers, Tumor

The study aimed to examine the effects of virtual reality (VR) technology-based phase I cardiac rehabilitation (CR) program in elderly coronary heart disease (CHD) patients after percutaneous coronary intervention (PCI). Thirty-six cases of elderly CHD patients who underwent PCI in the First Affiliated Hospital of Chongqing Medical University from June 2022 to April 2023 were recruited by convenience sampling method. The patients were randomly assigned by means of random digital table method to two study groups: control group (n = 18), which received conventional nursing intervention after PCI, and experimental group (n = 18), which received a combined program of conventional nursing intervention together with CR program based on VR technology. The 6 min walk test (6MWT), Simple Physical Performance Battery (SPPB), SF-36 scale, Hospital Anxiety and Depression Scale (HADS) and Impact of Events Scale-Revised (IES-R) were tested before and after rehabilitation. Moreover, the incidence of major adverse cardiovascular events (MACE) was recorded at 3 months after PCI. After VR-based CR, the 6MWT distance and SPPB scores of patients in the experimental group were higher than those in control group (P < 0.05). The HADS scores and IES-R scores of the patients in the experimental group were lower than those in control group (P < 0.01), and the difference in SF-36 scale scores was not statistically significant between two groups (P > 0.05). The incidence of MACE was not significantly different at 3 months after PCI (P > 0.05). These results suggest that VR-based phase I CR program mitigates the degree of PCI postoperative stress, anxiety, and depression in elderly CHD patients, however, enhances the resistance to fatigue and does not increase the risk of adverse cardiac events, suggesting it is a safe intervention.
Aged ; Humans ; Anxiety ; Cardiac Rehabilitation/methods* ; Coronary Disease/surgery* ; Percutaneous Coronary Intervention/adverse effects* ; Virtual Reality