This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

OBJECTIVE: To investigate the Wnt signaling pathway and miRNAs mechanism of extracts of Plastrum Testudinis (PT) in the treatment of osteoporosis (OP). METHODS: Thirty female Sprague Dawley rats were randomly divided into 5 groups by random number table method, including sham group, ovariectomized group (OVX), ovariectomized groups treated with high-, medium-, and low-dose PT (160, 80, 40 mg/kg per day, respectively), with 6 rats in each group. Except for the sham group, the other rats underwent bilateral ovariectomy to simulate OP and received PT by oral gavage for 10 consecutive weeks. After treatment, bone mineral density was measured by dual-energy X-ray absorptiometry; bone microstructure was analyzed by micro-computed tomography and hematoxylin and eosin staining; and the expressions of osteogenic differentiation-related factors were detected by immunochemistry, Western blot, and quantitative polymerase chain reaction. In addition, Dickkopf-1 (Dkk-1) was used to inhibit the Wnt signaling pathway in bone marrow mesenchymal stem cells (BMSCs) and miRNA overexpression was used to evaluate the effect of miR-214 on the osteogenic differentiation of BMSCs. Subsequently, PT extract was used to rescue the effects of Dkk-1 and miR-214, and its impacts on the osteogenic differentiation-related factors of BMSCs were evaluated. RESULTS: PT-M and PT-L significantly reduced the weight gain in OVX rats (P<0.05). PT also regulated the bone mass and bone microarchitecture of the femur in OVX rats, and increased the expressions of bone formation-related factors including alkaline phosphatase, bone morphogenetic protein type 2, collagen type I alpha 1, and runt-related transcription factor 2 when compared with the OVX group (P<0.05 or P<0.01). Meanwhile, different doses of PT significantly rescued the inhibition of Wnt signaling pathway-related factors in OVX rats, and increased the mRNA or protein expressions of Wnt3a, β-catenin, glycogen synthase kinase-3β, and low-density lipoprotein receptor-related protein 5 (P<0.05 or P<0.01). PT stimulated the osteogenic differentiation of BMSCs inhibited by Dkk-1 and activated the Wnt signaling pathway. In addition, the expression of miR-214 was decreased in OVX rats (P<0.01), and it was negatively correlated with the osteogenic differentiation of BMSCs (P<0.01). MiR-214 mimic inhibited Wnt signaling pathway in BMSCs (P<0.05 or P<0.01). Conversely, PT effectively counteracted the effect of miR-214 mimic, thereby activating the Wnt signaling pathway and stimulating osteogenic differentiation in BMSCs (P<0.05 or P<0.01). CONCLUSION PT stimulates bone formation in OVX rats through β-catenin-mediated Wnt signaling pathway, which may be related to inhibiting miR-214 in BMSCs.
Animals ; MicroRNAs/genetics* ; Female ; Rats, Sprague-Dawley ; Wnt Signaling Pathway/genetics* ; Osteogenesis/genetics* ; Mesenchymal Stem Cells/cytology* ; Cell Differentiation/drug effects* ; Bone Density/drug effects* ; Ovariectomy ; Osteoporosis/drug therapy* ; beta Catenin/metabolism* ; Rats ; Intercellular Signaling Peptides and Proteins/metabolism* ; Drugs, Chinese Herbal/pharmacology*

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Objective To observe the clinical effect of acupuncture at the core muscle group combined with rehabilitation training in the treatment of chronic non-specific low back pain.Methods A total of 96 patients with chronic non-specific low back pain were randomly divided into observation group and control group,48 cases in each group.The control group was given rehabilitation training,and the observation group was given acupuncture at core muscle group training on the basis of the control group.Patients in both groups were treated continuously for two weeks.After two weeks of treatment,the clinical efficacy of the two groups was evaluated.The changes of root mean square(RMS)values of transverse abdominal muscle and multifidus muscle were observed before and after treatment,as well as the scores of Oswestry Dysfunction Index,Roland-Morris Dysfunction Questionnaire and Quebec Low Back Pain Scale.The changes of serum β-endorphin,serum substance P and serum prostaglandin E2 levels were compared before and after treatment between the two groups.The patients were followed up for five months after treatment,and the recurrence of the two groups was evaluated.Results(1)The total effective rate was 93.75%(45/48)in the observation group and 81.25%(39/48)in the control group.The curative effect of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the Oswestry Dysfunction Index score,Roland-Morris Dysfunction Questionnaire score and Quebec Low Back Pain Disorder Scale score of the two groups were significantly improved(P＜0.05),and the improvement of Oswestry Dysfunction Index score,Roland-Morris Dysfunction Questionnaire score and Quebec Low Back Pain Disorder Scale score in the observation group was significantly superior to that in the control group,the difference was statistically significant(P＜0.05).(3)After treatment,the RMS values of transverse abdominal muscle and multifidus muscle in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the RMS values of transverse abdominal muscle and multifidus muscle,the difference being significant(P＜0.05).(4)After treatment,the levels of β-endorphin,substance P and prostaglandin E2 in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the levels of β-endorphin,substance P and prostaglandin E2,the differences were statistically significant(P＜0.05).(5)After treatment,the recurrence rate of the observation group was 6.25%(3/48),and that of the control group was 20.83%(10/48).The recurrence rate of the observation group was significantly lower than that of the control group,and the difference was statistically significant(P＜0.05).Conclusion Acupuncture at the core muscle group combined with rehabilitation training in the treatment of chronic non-specific low back pain can significantly improve the clinical symptoms of patients,improve the levels of β-endorphin,substance P and prostaglandin E2,and the clinical effect is significant.

AIM To study the flavonoids from the leaves of Cinnamomum camphora(L.)Presl.and their antioxidant activities.METHODS The 95％ethanol extraction from the leaves of C.camphora was isolated and purified by liquid-liquid extraction,macroporous adsorption resin chromatography,HW-40C gel column chromatography,molecular exclusion chromatography and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activity was determined by DPPH method.RESULT Ten flavonoids were isolated and identified as(2R,3S)-7-methoxy-5-O-β-D-glucopyranosyl-afzelechin(1),quercetin-3-O-sambubioside(2),quercetin-3-O-β-D-apiosyl-(1→2)-β-D-glucoside(3),quercetin-3-O-robibioside(4),kaempferol-3-O-β-D-rutinoside-7-O-β-D-glucoside(5),kaempferol-3-O-α-L-rhamnoside-7-O-β-D-glucoside(6),5,3'-di-O-methyl-epicatechin(7)、cinchonain Ⅱb(8)、quercetin-3,4'-di-O-β-D-glucoside(9)、(-)-epicatechin(10).The IC50 value of compound 8 scavenging DPPH free radical was 4.8 μg/mL.CONCLUSION Compound 1 is a new compound,and compound 2-6 are obtained from Cinnamomum genus for the first time,compound 7-9 are first isolated from this plant.Compound 8 shows good antioxidant activities..

Sesquiterpenes are natural terpenoids with 15 carbon atoms in the basic skeleton, which mainly exist in plant volatile oil and have important physiological and medicinal value. Cytochrome P450 (CYP450) is a kind of monooxygenase encoded by supergene family, which is one of the largest gene families in plants. It is involved in the synthesis and metabolism of terpenoids, alkaloids and other secondary metabolites. In the process of terpene biosynthesis, CYP450 participates in the post-modification stage of terpenes by introducing functional groups such as hydroxyl, carboxyl and carbonyl, which plays an important role in enriching the diversity of terpenes. The CYP450 enzymes involved in sesquiterpene synthesis and their substrate catalytic specificity mechanisms have been partially investigated. In this paper, the biosynthetic pathway of plant sesquiterpenes, the structure and classification of CYP450 enzymes were briefly introduced, and the CYP450 enzymes involved in sesquiterpene biosynthesis were summarized, in order to provide a reference for intensive study of the role of CYP450 enzymes in the synthesis of sesquiterpenoids.

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC₅₀) and selectivity index (SI) values of 2.36 μmol·L^-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (K_D) value of 1.36 μmol·L^-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

Objective To observe the efficacy of dapagliflozin tablets combination with sacubitril/valsartan sodium tablets in the treatment of patients with heart failure(HF)after acute myocardial infarction(AMI)intervention.Methods Patients with HF after AMI intervention were randomly divided into control group and treatment group.The control group was given conventional anti-heart failure therapy+sacubitril/valsartan sodium tablets(50 mg for the first time,then gradually increased to 200 mg each time,twice a day),and the treatment group was additionally treated with dapagliflozin(10 mg every time,once a day)on the basis of the control group,and the course of treatment was 6 months.The two groups were compared in terms of clinical efficacy,cardiac function[left ventricular ejection fraction(LVEF),left ventricular remodeling index(LVRI),6-minute walking distance(6MWD)],heart failure markers[brain natriuretic peptide(BNP),N-terminal pro-brain natriuretic peptide(NT-proBNP),troponin(Tn)],and serum related biochemical indicators[soluble human stromelysin-2(ST2),angiotensin 2(AT-Ⅱ),soluble intercellular adhesion molecule-1(sICAM-1)],incidence rates of major adverse cardiovascular events(MACE)during follow-up and adverse drug reactions during treatment.Results Six cases dropped out during treatment,and finally 46 cases were included in control group and treatment group,respectively.After treatment,the effective rates of treatment in treatment group(91.30％)was significantly higher than that in control group(76.09％,P＜0.05).After treatment,the LVEF values in control group and treatment group were(51.38±4.82)％and(54.43±4.63)％;LVRI values were(1.47±0.15)and(1.35±0.17)g·mL-1;6MWD values were(390.53±40.32)and(362.61±38.51)m;the BNP levels were(28.34±2.47)and(26.51±2.16)pmol·L-1;NT-proBNP levels were(262.61±53.18)and(227.68±46.73)ng·L-1;sICAM-1 levels were(84.61±7.14)μg·L-1 and(74.68±7.08)μg·L1,and there were statistical differences between both groups(all P＜0.05).During follow-up,the incidence rate of MACE in treatment group(6.52％)was significantly lower than that in control group(21.74％,P＜0.05).The main adverse drug reactions in the two groups were renal dysfunction,hypotension,urogenital infection and hyperkalemia,but there was no significant difference in the incidence of adverse reactions between treatment group(13.04％)and control group(10.87％,P＞0.05).Conclusion Dapagliflozin tablets combined with sacubitril/valsartan sodium tablets can significantly improve cardiac function and related indicators and reduce the incidence of MACE in patients with HF after AMI intervention.