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 effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Objective To analyze the current status and hotspots of surgical transmural ablation of atrial fibrillation using CiteSpace and VOSviewer. Methods The Web of Science Core Collection database was used as the data source. The CiteSpace 5.8.R3 and VOSviewer software were used to analyze the related studies on surgical transmural ablation of atrial fibrillation about the authors, countries/institutions, literature co-citation and keywords. Results A total of 109 articles were enrolled. Damiano RJ was the most prolific researcher, while Cox JL was the author with the highest number of citations. The United States was the leading country in this research field. The University of Washington was an important institution in the study of atrial fibrillation transmural ablation. The main hotpots were the effectiveness of surgical ablation, especially Cox-maze procedure, selection of the energy source of surgical ablation, combination of surgical and catheter ablations, and pulmonary vein isolation. Conclusion This study visualizes the current research status of surgical ablation of atrial fibrillation. How to improve the effectiveness and transmurality of surgical ablation is a hot research topic in the surgical treatment of atrial fibrillation. The combination of electrophysiology mapping and surgical ablation may be the development direction in the surgical treatment of atrial fibrillation.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To study the effect of microRNA-183(miR-183)on the growth and development of ze-brafish inner ear,and its mechanism in the regeneration and growth of inner ear hair cells,otocyst and otolith in-jured by cisplatin.Methods Synthesized miRNAs(agomir)and antisense morpholino oligonucleotides(MOs)were injected into zebrafish embryos by microinjection to construct the model of these miRNAs'levels.The 72-hours post fertilization zebrafish were immersed in 50 μmol/L cisplatin for 24 hours.MiRNA microarray analysis,RT-qPCR and other techniques were used to detect the changes of miR-183 and FOXO1 gene expression.FM1-43FX fluores-cence staining was used to understand the injury and regeneration of inner ear nerve thalamic hair cells.The micro-scope was used to observe the growth and development of otocyst and otoliths.Results ① After the treatment of cisplatin,the inner ear hair cells of zebrafish were damaged and the growth and development of otocyst and otoliths were hindered.After the removal of cisplatin,the inner ear hair cells could be regenerated,and the growth and de-velopment of otocyst and otoliths also recovered gradually.② miR-183 was activated after the removal of cisplatin,which was one of the most differentially expressed members in zebrafish larva miRNA(P＜0.001),and the expres-sion level increased continuously to the peak and then gradually returned to the normal level.③ Compared with the control group,after the removal of cisplatin,the overexpression of miR-183 could promote the recovery of the num-ber of hair cells and the area of otocyst and otoliths,while the recovery was inhibited in the group with low expres-sion of miR-183.④ After the removal of cisplatin,FOXO1 was activated and the expression was up-regulated(P＜0.01).When miR-183 was overexpressed,FOXO1 was inhibited and expression was down-regulated(P＜0.01).Conversely,when miR-183 was low,the expression of FOXO1 increased(P＜0.01).Conclusion The increase of miR-183 expression occurs simultaneously with the regeneration of inner ear hair cells and the recovery of growth and development of the otolith area after cisplatin removal.The overexpression or low expression of miR-183 can promote or inhibit the regeneration of inner ear hair cells and the recovery of growth and development of the otolith area,indicating that there is a positive regulatory relationship between them.The mechanism may be related to the negative regulation of miR-183 on FOXO1.

To sum up integrative nursing experience of a case with chronic refractory wound formation caused by drug extravasation.The essentials of integrative nursing are:structured nursing intervention of"assessment-management-treatment"based on the Triangle of Wound Assessment;determination of the timing for integrative nursing according to the theory of TCM sores and ulcers;implementation of copper board scraping method to promote circulation of qi and blood;use of Huo-long Comprehensive Moxibustion Therapy to promote muscle regeneration.With the help of the cooperation of the multidisciplinary specialist nursing team,the wound was completely healed after 59 days of integrated traditional Chinese and Western medicine nursing interventions.

Objective To evaluate the clinical value of single-pill combination(SPC)of perindopril and amlodipine for the treatment of hypertension and provide reference for the selection and rational use in medical institutions.Methods A comprehensive clinical evaluation index system was established based on literature research and expert demonstration.Therefore,the safety,effectiveness,economy,innovation,suitability and accessibility of drugs were analyzed qualitatively and quantitatively.Results A total of 12 studies reported the outcome of perindopril and amlodipine SPC,including efficacy and safety.Perindopril amlodipine SPC was safe,and there was no significant difference in the incidence of adverse events during treatment compared with monotherapy,monotherapy combination or other antihypertensive SPC.In terms of effectiveness,perindopril and amlodipine SPC had clear antihypertensive effect,which could significantly reduce systolic blood pressure,diastolic blood pressure,pulse pressure difference and heart rate,and the blood pressure compliance rate of perindopril and amlodipine SPC was better than that of amlodipine or perindopril monotherapy group.Compared with other depressurized SPCs,it showed better or non-inferior effect.Perindopril amlodipine SPC,as a patented drug,has good innovation,high patient compliance,and has been included in China's medical insurance catalog,but the current medical institutions have a low supply rate,and drug prices and affordability are still at a relatively high level.Conclusion Perindopril amlodipine SPC has significant advantages in safety,effectiveness,suitability and innovation,but its economy and accessibility still need to be improved.

Objective: To explore the clinical effects of island posterior femoral composite tissue flaps in the repair of sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter. Methods: The retrospective observational study was conducted. From December 2018 to December 2021, 23 patients with sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter who met the inclusion criteria were admitted to Ganzhou People's Hospital, including 16 males and 7 females, aged 45 to 86 years. The size of pressure ulcers in ischial tuberosity ranged from 1.5 cm×1.0 cm to 8.0 cm×5.0 cm, and the size of pressure ulcers in greater trochanter ranged from 4.0 cm×3.0 cm to 20.0 cm×10.0 cm before debridement. After treatment of underlying diseases, debridement and vacuum sealing drainage for 5 to 14 days were performed. All the wounds were repaired by island posterior femoral composite tissue flaps, with area of 4.5 cm×3.0 cm-24.0 cm×12.0 cm, pedicle width of 3-5 cm, pedicle length of 5-8 cm, and rotation radius of 30-40 cm. Most of the donor site wounds were sutured directly, and only 4 donor site wounds were repaired by intermediate thickness skin graft from the contralateral thigh. The survival of composite tissue flaps, wound healing of the donor and recipient sites and the complications were observed. The recurrence of pressure ulcers, and the appearance and texture of flaps were observed during follow-up. Results: A total of 32 wounds in 23 patients were repaired by island posterior femoral composite tissue flaps (including 3 fascio subcutaneous flaps, 24 fascial flaps+fascio subcutaneous flaps, 2 fascial flaps+fascial dermal flaps, 2 fascial flaps+fascio subcutaneous flaps+femoral biceps flaps, and one fascial flap+fascio subcutaneous flap+gracilis muscle flap). Among them, 31 composite tissue flaps survived well, and a small portion of necrosis occurred in one fascial flap+fascio subcutaneous flap post surgery. The survival rate of composite tissue flap post surgery was 96.9% (31/32). Twenty-nine wounds in the recipient sites were healed, and 2 wounds were torn at the flap pedicle due to improper postural changes, and healed one week after bedside debridement. One wound was partially necrotic due to the flap bruising, and healed 10 days after re-debridement. Thirty-one wounds in the donor sites (including 4 skin graft areas) were healed, and one wound in the donor site was torn due to improper handling at discharge, and healed 15 days after re-debridement and suture. The complication rate was 12.5% (4/32), mainly the incision dehiscence of the flap pedicle and the donor sites (3 wounds), followed by venous congestion at the distal end of flap (one wound). During the follow-up of 3 to 24 months, the pressure ulcers did not recur and the flaps had good appearance and soft texture. Conclusions: The island posterior femoral composite tissue flaps has good blood circulation, large rotation radius, and sufficient tissue volume. It has a high survival rate, good wound healing, low skin grafting rate in the donor site, few postoperative complications, and good long-term effect in the repair of sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter.
Male ; Female ; Humans ; Plastic Surgery Procedures ; Pressure Ulcer/etiology* ; Soft Tissue Injuries/surgery* ; Treatment Outcome ; Skin Transplantation ; Femur/surgery* ; Necrosis/surgery* ; Perforator Flap

OBJECTIVE: To explore the effect and mechanism of schisandrin B (Sch B) in the treatment of cerebral ischemia in rats. METHODS: The cerebral ischemia models were induced by middle cerebral artery occlusion (MCAO) and reperfusion. Sprague-Dawley rats were divided into 6 groups using a random number table, including sham, MCAO, MCAO+Sch B (50 mg/kg), MCAO+Sch B (100 mg/kg), MCAO+Sch B (100 mg/kg)+LY294002, and MCAO+Sch B (100 mg/kg)+wortmannin groups. The effects of Sch B on pathological indicators, including neurological deficit scores, cerebral infarct volume, and brain edema, were subsequently studied. Tissue apoptosis was identified by terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining. The protein expressions involved in apoptosis, inflammation response and oxidative stress were examined by immunofluorescent staining, biochemical analysis and Western blot analysis, respectively. The effect of Sch B on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling was also explored. RESULTS: Sch B treatment decreased neurological deficit scores, cerebral water content, and infarct volume in MCAO rats (P<0.05 or P<0.01). Neuronal nuclei and TUNEL staining indicated that Sch B also reduced apoptosis in brain tissues, as well as the Bax/Bcl-2 ratio and caspase-3 expression (P<0.01). Sch B regulated the production of myeloperoxidase, malondialdehyde, nitric oxide and superoxide dismutase, as well as the release of cytokine interleukin (IL)-1 β and IL-18, in MCAO rats (P<0.05 or P<0.01). Sch B promoted the phosphorylation of PI3K and AKT. Blocking the PI3K/AKT signaling pathway with LY294002 or wortmannin reduced the protective effect of Sch B against cerebral ischemia (P<0.05 or P<0.01). CONCLUSIONS Sch B reduced apoptosis, inflammatory response, and oxidative stress of MCAO rats by modulating the PI3K/AKT pathway. Sch B had a potential for treating cerebral ischemia.