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 efficacy of minimally invasive osteotomy with preservation of blood supply to the transversely transported bone segment in the treatment of chronic ischemic lower limb diseases using tibial transverse bone transport. METHODS: A retrospective analysis was conducted on the clinical data of 12 patients with chronic ischemic lower limb diseases who met the selection criteria and were treated between June 2016 and December 2023. The cohort included 7 males and 5 females, aged 26-87 years (mean, 61.2 years). Among them, 7 patients had diabetic foot (DF), including 2 cases complicated by arteriosclerosis obliterans (ASO), with a DF duration ranging from 1.7 to 23.0 months (mean, 9.6 months) and ulcer sizes ranging from 3.2 cm×2.4 cm to 10.0 cm×6.6 cm. Three patients had ASO with a disease duration of 1.7-23.0 months (mean, 10.4 months) and ulcer or post-amputation wound sizes ranging from 2.2 cm×2.1 cm to 12.0 cm×7.7 cm. Additionally, 2 patients with thromboangiitis obliterans (TAO) had a disease duration of 7 and 12 months, respectively. Preoperatively, the mean foot skin temperature was (27.63±0.34)℃, and the visual analogue scale (VAS) score was 8.5±0.7. All patients underwent tibial transverse bone transport using minimally invasive osteotomy while preserving the blood supply to the transported bone segment. Postoperative complications and foot ulcer healing were observed. The effectiveness of tibial transverse bone transport was evaluated by comparing preoperative and postoperative foot skin temperature, VAS scores, as well as through CT angiography (CTA). RESULTS: One DF patient with ASO was lost to follow-up, while the remaining 11 patients were followed up 10-29 months (mean, 20.5 months). One DF patient had a displaced fracture at the site of tibial transport due to trauma, which healed after plaster immobilization; 1 DF patient had a small amount of pigmentation in the skin of the donor site, but the blood circulation was good; no complication such as pin tract infection, skin necrosis, or osteomyelitis occurred in the donor site of all patients. At 2-3 weeks postoperatively, the foot skin temperature was (34.21±0.65)℃, and the VAS score was 0.3±0.1, both significantly improved compared to preoperative ones ( t=-31.578, P<0.001; t=49.000, P<0.001). Two TAO patients experienced recurrent, persistent, intolerable pain at 7-10 days postoperatively, with no reduction in ulcer size or necrotic areas; 1 underwent toe amputation, and the other required a mid-leg amputation. The remaining patients achieved complete ulcer healing, with healing time ranging from 5.1 to 9.2 weeks (mean, 6.8 weeks). CTA showed no new vascular occlusions or embolisms. X-ray films at 4 months postoperatively demonstrated proper repositioning and good healing of the transported tibial bone segment. CONCLUSION The application of minimally invasive osteotomy with preserved blood supply to the transversely transported bone segment in tibial transverse bone transport for the treatment of chronic ischemic lower limb diseases effectively minimizes extensive soft tissue dissection, reduces surgical soft tissue damage, and better maintains local blood supply. This approach lowers the risk of postoperative infection and skin necrosis while accelerating postoperative recovery.
Humans ; Osteotomy/methods* ; Middle Aged ; Male ; Female ; Aged ; Tibia/surgery* ; Minimally Invasive Surgical Procedures/methods* ; Retrospective Studies ; Adult ; Bone Transplantation/methods* ; Aged, 80 and over ; Diabetic Foot/surgery* ; Treatment Outcome ; Arteriosclerosis Obliterans/surgery* ; Ischemia/surgery* ; Lower Extremity/blood supply*

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 investigate the impact of osteotomy mode on the callus morphology in the ex-tension area of tibial bone transfer and its efficacy.Methods The information of the patients with bone defect treated in 910 Hospital of Joint Logistics and Security Force of Chinese People's Liberation Army from May 2016 to June 2022 was collected.By comparing the general data of the patients with different osteotomy meth-ods(minimally invasive osteotomy group,subperiosteal osteotomy group and extraperiosteal osteotomy group),callus morphology in the extension area(sunken type,uniform type and protruding type),healing in-dex,Ilizarov Method Research and Application Society(ASAMI)bone healing and functional evaluation and other information,the curative effect differences of different osteotomy methods on tibial bone transfer were investigated.Results The incidence rate of sunken type of callus in the extension area was 15.8%in the mini-mally invasive osteotomy group,18.9%in the subperiosteal osteotomy group,and 14.3%in the extraperioste-al osteotomy group,with statistically significant differences among the three groups(P<0.05);in which,the incidence of sunken type of callus in the minimally invasive osteotomy group was lower than that in the subpe-riosteal osteotomy group(χ2=10.178,P=0.005),but there was no statistically significant difference when compared to the extraperiosteal osteotomy group(χ2=0.102,P=0.814),the difference betrrween the extra-periosteal osteotomy group and subperiosteal osteotomy group also had no statistical difference(χ2=0.084,P=0.772).The incidence rate of uniform type of callus in the minimally invasive osteotomy group was lower than that in the subperiosteal osteotomy group(χ2=6.579,P=0.013),but there was no statistically signifi-cant difference when compared to the extraperiosteal osteotomy group(χ2=0.443,P=0.506).The difference in the subperiosteal osteotomy group and extraperiosteal osteotomy group also had no statistically significant(χ2=2.602,P=0.107).The incidence rate of protruding type of callus in the minimally invasive osteotomy group was higher than that in the subperiosteal osteotomy group(χ2=9.795,P=0.002),and the incidence rate of protruding type of callus in the extraperiosteal osteotomy group was higher than that in the subperios-teal osteotomy group(χ2=5.170,P=0.023),however,there was no statistically significant difference be-tween the minimally invasive osteotomy group and the extraperiosteal osteotomy group(χ2=0.308,P=0.579).There were no statistically significant differences in healing index,ASAMI scores,contact point non-union,pin tract infection and refracture incidence rate rates among the three groups(P>0.05).Conclusion Sub-periosteal osteotomy in the single plane tibial bone moving does not show the expected results in favor of the extension area mineralization,on the contrary,extraperiosteal osteotomy has the similar clinical efficacy to minimally invasive osteotomy.

Objective To investigate the changes in the gut microflora(GM)composition and metabo-lites in children with allergic rhinitis(AR)based on high-throughput sequencing technology.Methods From December 2023 to May 2024,11 preschool children with allergic rhinitis(AR)who visited the pediatric outpa-tient department of Shantou University Medical College Longgang Maternal and Child Health Hospital Clini-cal College(Longgang District Maternal and Child Health Hospital)were selected as the AR group,and 21 healthy children of the same age who underwent physical examinations in the child health care department during the same period were selected as the control group.Fecal samples were collected from both groups,and DNA was extracted and amplified.High-throughput sequencing technology was used to analyze the composi-tion of gut microbial genes,and the differences in gut microbiota composition and metabolites between the two groups were compared.Results Compared with the control group,the AR group had a higher Shannon index,with a significant increase in the abundance of Proteobacteria and Saccharibacteria.The relative abundance of Veillonella,Enterococcus,Escherichia coli/Shigella,Haemophilus,and Streptococcus was significantly high-er,while the relative abundance of Lachnospira,Anaerostipes,Enterobacteriaceae,Anaerobacterium,and Eu-bacterium was significantly lower(P＜0.05).There were statistically significant differences in the principal components of GM metabolites between the two groups(P＜0.05).A total of 2 540 different metabolites were identified,of which 1 185 metabolites were significantly increased,20 metabolites were significantly de-creased,and 1 335 metabolites showed no significant changes.Variable importance in projection(VIP)analy-sis revealed 30 significantly different metabolites.Compared with the control group,2 fecal metabolites were significantly downregulated in the AR group,specifically 3-furanmethanol glucoside and membrane heptosyl A.Conclusion The gut microbiota of preschool children with AR has undergone significant changes,which are related to inflammation and immune function.

Thyroid cancer is the common malignant tumor in the neck, and surgery is the important treatment measure for it. Some patients suffer from hypoparathyroidism and hypocalcemia after thyroidectomy, which will seriously affect the patient’s life quality and prognosis. This article reported a case of 42 years old female patient with hypocalcemia for 6 years after total thyroidectomy due to thyroid cancer, who still had frequent hypocalcemia with high dose of oral calcium and active vitamin D supplementation. Long-term and frequent facial and limb numbness, convulsions, epileptic-like seizures and sudden unconsciousness afflicted her due to hypocalcemia. After admission, her symptoms were obviously relieved after one week of adequate calcium supplementation through oral administration or intravenous infusion under close monitoring. Upon discharge she was able to maintain the normal level of blood calcium by decreased dose of oral calcium supplementation alone. Long-term limb numbness, convulsions, low back pain, shoulder pain, walking instability and other symptoms disappeared basically. The epileptic-like seizures did not recur. During six months of follow-up, her blood calcium was still well controlled in normal level.

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 investigate the expression of N6-methyladenosine(m6A) modification-related genes and their possible roles in peripheral blood mononuclear cells (PBMCs) of patients with primary gouty arthritis (GA).Methods:Forty-five patients each with acute gout (AG), intermittent gout (IG), and age-and gender-matched healthy controls (HC) were collected from the outpatient clinic of the Department of Rheumatology and Immunology of the Affiliated Hospital of Chuanbei Medical College between October and December of 2023. The expression levels of m6A modification-related genes (METTL3、METTL14、WTAP、FTO、ALKBH5、IGF2BP2、IGF2BP3、YTHDF1、YTHDC2) in PBMCs among the 3 groups were detected by RT-qPCR and correlation analysis with clinical indicators was performed. Measurements conforming to normal distribution were analyzed using ANOVA or t-tests, and data were analyzed using the Kruskal-Wallis H-test and Mann-Whitney U-test for data that is not-normaly distributed. The value of m6A modification-related genes for the diagnosis of GA was evaluated using subject characterization curve ROC. Results:①There were statistically significant differences in the expression of IGF2BP2 ( Z=-3.59, P<0.001)、WTAP ( Z=-5.25, P<0.001)、METTL14 ( Z=-3.62, P<0.001)、YTHDF1 ( Z=-2.12, P=0.034)and YTHDC2 ( Z=-2.00, P=0.045) in the disease group and the normal control group. Among them, the expression of IGF2BP2 in the GA group [28.08 (17.99, 47.06)×10 -4] was significantly higher than that in the HC group [19.23 (12.90, 25.78)×10 -4], and the expressions of WTAP、METTL14、YTHDF1 and YTHDC2 in the GA group [298.61 (213.61, 377.80)×10 -4, 9.94 (6.43, 13.46)×10 -4, 52.63 (28.22, 72.77)×10 -4, 40.24 (20.74, 73.32)×10 -4] were significantly lower than those in the HC group [398.45(339.88, 454.89)×10 -4, 13.27(11.07, 15.85)×10 -4, 64.43(43.61, 87.10)×10 -4, 53.11(36.37, 79.28)×10 -4]. Further subgroup analysis revealed statistically significant differences in the expression of IGF2BP2、WTAP、METTL14、YTHDF1 and YTHDC2 among the 3 groups ( H=19.62、31.73、13.14、16.64、28.90, all P≤0.001). The expressions of WTAP and METTL14 in the AG group [311.13(234.96, 426.67)×10 -4, Z=-3.27, P=0.001; 9.64 (5.21, 15.21)×10 -4, Z=-2.71, P=0.008] and IG group [272.27 (203.29, 347.95)×10 -4, Z=-5.78, P<0.001; 10.40(6.88, 12.88)×10 -4, Z=-3.54, P=0.003] were lower than those in the HC group [398.45 (339.88, 454.89)×10 -4, 13.27(11.07, 15.85)×10 -4]. However, there was no significant difference between AG and IG group ( P>0.05). Both YTHDF1 and YTHDC2 were significantly lower in the AG group [38.10(16.19, 56.78)×10 -4, 24.31 (14.35, 42.77)×10 -4] than those in the IG group [64.13 (48.28, 74.40)×10 -4(Z=-3.54, P<0.001, 65.49 (39.89, 91.23)×10 -4(Z=-4.96, P<0.001)] and HC group [64.43 (43.61, 86.92)×10 -4(Z=-3.51, P<0.001), 53.11 (36.37, 79.28)×10 -4(Z=-4.25, P<0.001)]. But there was no statistically significant difference between IG and HC groups ( P>0.05); IGF2BP2 was significantly lower in the AG group [25.32(16.40, 40.43)×10 -4, Z=-2.46, P=0.014] and HC group [19.23 (12.90, 25.78)×10 -4, Z=-4.54, P<0.001] than in the IG group [31.10(22.60, 49.58)×10 -4], but the comparison between AG and HC showed no statistically significant difference( P>0.05). ②Spearman correlation analysis showed that in GA patients, the expression of IGF2BP2、METTL14 and YTHDF1 was positively correlated with plasma glucose、blood uric acid(sUA) and total cholesterol level respectively ( r=0.22, P=0.037; r=0.38, P=0.003; r=0.23, P=0.034), and WTAP was negatively correlated with GLU ( r=-0.25, P=0.020). ③The ROC curve for the joint prediction of the five differential genes showed that the 95% CI for area under the curve in GA was 0.90 (0.84, 0.95). Conclusion:The m6A modification-related genes are abnormally expressed in GA and are correlated with clinical indicators such as GLU and UA, which are hypothesized to be involved in the pathogenesis of GA and have a certain reference value for the evaluation of metabolism in GA patients.

Objective To establish and validate a method for simultaneous determination of 9 sedative-hypnotics in human plasma,and to explore the preliminary clinical application.Methods Plasma samples were precipitated with acetonitrile and determined by high performance liquid chromatography tandem mass spectrometry.The column was Agilent Poroshell 120 EC-C18(2.1 mm × 50.0 mm,2.7μm)and eluted with acetonitrile water containing 0.1％formic acid in an equal degree program at a flow rate of 0.3 mL·min-1.The column temperature was 20 ℃ and injection volume was 5 μL.The deprotonated ions of analytes were ionized by positive ion,electron spray ionization and multiple reaction monitoring mode.The specificity,standard curve and lower limit of quantification,precision and recovery,matrix effect,stability and dilution effect of the method were investigated.Results Excellent linear relationship with correlation coefficient of r2 ≥ 0.997 7 was obtained.The linear of esazolam,alprazolam,oxazepam,clonazepam,lorazepam,triazolam,midazolam,diazepam and zolpidem were 18-1 800,4.5-450,25-2 500,3.5-350,25-2 500,1.5-150,5.5-550,35-3 500,4-400 ng·mL-1,respectively.The lower limit of quantification were 18,4.5,25,3.5,25,1.5,5.5,35,4 ng·mL-1.The method was accurate and precise with acceptable intra-day and inter-day precisions(relative standard deviations were less than 20％for a lower limit of quantification and less than 15％for other quality control samples)and an accuracy of 86.21％-112.38％.The extraction recovery rate were 93.07％-110.50％.The matrix factors normalized by internal standard were 86.61％-108.41％,relative standard deviations were less than 15％.Plasma samples remained stable under various storage conditions.The precision and accuracy of plasma samples were acceptable after dilution.Conclusion The method is simple,rapid,sensitive and specific,and it can be used for simultaneous detection of the 9 sedative-hypnotics in human plasma.