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 evaluate the clinical efficacy of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus traditional Chinese medicine(TCM)bone-setting manipulations for the treatment of moderate hallux valgus.Methods A retrospective study was conducted.A total of 49 patients(62 feet)with moderate hallux valgus were treated with Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate,and were given TCM bone-setting manipulations before the operation,during the operation,and after the operation.The efficacy was evaluated by using the Visual Analogue Scale(VAS)score and the American Orthopedic Foot and Ankle Society(AOFAS)forefoot score after the operation.Before the operation and 12 months after the operation,the hallux valgus angle(HVA),intermetatarsal angle(IMA)between the first and second metatarsal bone,and the distal metatarsal articular angle(DMAA)showed by X-ray imaging in the weight-bearing position of the foot were recorded.Results(1)All of the 49 patients were followed up for 12 to 24 months,with a mean of(20.6±3.1)months.(2)The X-ray imaging assessment showed that 12 months after the operation,the mean HVA,IMA and DMAA values of the 49 patients(62 feet)were significantly lower than those before the operation,and the differences were all statistically significant(P＜0.01).(3)Twelve months after the operation,the pain VAS score of 49 patients was(3.14±1.21)points,which was significantly lower than the preoperative score points(7.26±2.52),and the difference was statistically significant(P＜0.01).(4)The assessment of joint function showed that 12 months after the operation,the scores of various AOFAS items of pain,function and hallux alignment as well as the overall AOFAS scores of 49 patients were significantly higher than those before the operation,and the differences were statistically significant(P＜0.01).(5)For the 62 feet in 49 patients,the excellent efficacy was achieved in 53 feet,good efficacy was achieved in 7 feet,and fair efficacy was achieved in 2 feet,with the fine rate of 96.77%(60/62).Conclusion For the treatment of moderate hallux valgus,the application of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus TCM bone-setting manipulations is effective on promoting the reset of hallux-metatarsophalangeal joint,restoring the balance of the joint,and maintaining the equilibrium state of the joint through postoperative rehabilitation guidance.The combined therapy exerts certain efficacy,reduces the recurrence rate,and eventually achieves the early rehabilitation after the operation.

Atherosclerosis （AS） is a chronic inflammatory pathological process in which lipid and/or fibrous substances are deposited in the intima of arteries， and it is one of the pathological bases of many cardiovascular and cerebrovascular diseases. Endoplasmic reticulum stress （ERS） is a protective mechanism of cell adaptation. Moderate ERS can reduce abnormal protein aggregation and increase the degradation of misfolded proteins to repair and stabilize the internal environment， while excessive ERS can cause unfolded protein reaction， activate inflammation， oxidative stress， apoptosis， autophagy， and other downstream pathways， and lead to cell damage， or even apoptosis. A large number of studies have shown that ERS mediates a variety of pathological processes related to AS， affects endothelial cells， smooth muscle cells， macrophages， endothelial progenitor cells， and other cell components closely related to its occurrence and development， influences the progress of AS by regulating cell function， and promotes the formation of AS plaque， the transformation of stable plaque to unstable plaque， and the rupture of unstable plaque. Regulation of ERS may be a key target for the prevention and treatment of AS， and it is a research hotspot at present. Traditional Chinese medicine （TCM） believes that the origin of AS is the imbalance of Yin and Yang， the disharmony of Zangfu organs， and the abnormal operation of Qi， blood， and body fluid， which leads to the accumulation of phlegm， blood stasis， and other pathological products in the pulse channels， making the blood flow blocked or misfunction and causing the disease， which belongs to the syndrome of deficiency in origin and excess in superficiality. As the pathogenesis of AS is complex， and the symptoms are diverse， TCM has significant advantages in treating AS because of its multiple targets， multiple pathways， stable efficacy， strong individualization， and high safety. This paper systematically elaborated on the role of ERS in the occurrence and development of AS and summarized the mechanism research on the regulation and control of ERS by Chinese herbal monomer， Chinese herbal extract， Chinese herbal compound， and proprietary medicine， so as to provide a theoretical basis for clinical research and drug development in the prevention and treatment of AS.

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

ObjectiveTo explore the effects of different emulsion mixtures and emulsification methods on the inflammation severity in an experimental autoimmune uveitis （EAU） model in rats， and to analyze the characteristics of the current EAU model. MethodEAU was induced in Lewis rats by subcutaneous injection of interphotoreceptor retinoid-binding protein （IRBP） 1177-1191 emulsified with Freund's complete adjuvant （CFA）， with or without intraperitoneal injection of pertussis toxin （PTX）. Slit lamp examination， HE staining， and optical coherence tomography were used to evaluate factors affecting EAU modeling， including different doses of the emulsion mixture （IRBP1177-1191， PTX， and inactivated Mycobacterium tuberculosis） and four different emulsification methods. The classification， characteristics， modeling methods， advantages， and disadvantages of EAU animal models were summarized and analyzed based on the clinical diagnostic criteria and syndrome characteristics of chronic uveitis in both traditional Chinese medicine （TCM） and western medicine， to evaluate the consistency between TCM and western medical syndromes. ResultIncreasing the dose of inactivated M. tuberculosis and antigen peptide in the emulsion mixture exacerbated the anterior segment inflammation in EAU rats. Increasing the injection of PTX also exacerbated anterior segment inflammation and increased retinal thickness in EAU rats. The severity of the EAU model was closely related to the emulsification method used. All four emulsification methods successfully induced EAU in rats. Comparatively， the ultrasonic cell disruptor and T10 basic disperser achieved successful emulsification in a short time. The degree of emulsification of the mixture also influenced the severity of the EAU model in rats. The existing EAU animal model shows a high degree of consistency with western medical diagnoses and the main ocular syndromes in TCM. ConclusionIRBP1177-1191， PTX， inactivated M. tuberculosis， and emulsification methods can affect the severity of the EAU model through different pathways. The existing EAU animal models can simulate the clinical characteristics of western medicine well but lack the etiology， pathogenesis， and syndrome characteristics of TCM. Therefore， it is necessary to construct an EAU animal model that combines disease and syndrome characteristics.

ObjectiveTo explore the possible mechanism of Changweiqing （肠胃清） in the treatment of colorectal cancer. MethodsHCT 116 cancer cells were used to prepare intestinal cancer cells with silenced polypyrimidine region binding protein 3 （PTBP3） gene and stably transfected cells with overexpressed PTBP3 gene. Stably transfected cells with silenced PTBP3， stably transfected cells with overexpressed PTBP3 and untransfected cancer cells were injected into the armpit of 72 nude mice to construct three different subcutaneous transplanted tumor models of colorectal cancer cells， including the silenced model， the overexpressed model and the control model， with 24 mice per model. Mice of each transplanted tumor modelwere randomly divided into Changweiqing （CWQ） group， oxaliplatin （OXA） group and normal saline （NS） group， with 8 mice in each group. The CWQ groups were given intragastric administration of 35.9625 g/kg of Changweiqing oral liquid and were intraperitoneally injected with 0.2ml of normal saline； the NS groups were given 0.5ml of normal saline by gavage， and intraperitoneal injection of 0.2ml of normal saline； the OXA groups were intraperitoneally injected with 5 mg/kg （0.2 ml） of oxaliplatin and given 0.5ml of normal saline by gavage. Each group was given intragastric administration once a day and intraperitoneal injection three times a week. After 31 days， the weight of subcutaneous tumors in each group was measured， and the tumor inhibition rate of the groups in each model were measured. Immunohistochemistry and other methods were used to detect the expression level of cell proliferation cell nuclear antigen Ki67 and apoptosis index. Real-time PCR and Western Blot were used to detect mRNA and protein expressions of PTBP3， signal transducer and activator of transcription 3 （STAT3） splicing isoform α （STAT3α）， STAT3 splicing isoform β （STAT3β）， B-cell lymphoma/leukemia-2 （Bcl-2） splicing isoform α （Bcl-2α）， and Bcl-2 splicing isoform β （Bcl-2β） in subcutaneous tumor cells in each group. ResultsFor all three transplanted tumor models， the weight of the subcutaneous tumors and Ki67 expression level of subcutaneous tumor tissue in all CWQ groups and OXA groups were lower than those of the corresponding NS groups， while the apoptosis level were higher （P＜0.05 or P＜0.01）. The mRNA and protein expressions of PTBP3， STAT3α， and Bcl-2α in the subcutaneous tumor tissues of the silenced model CWQ group and the overexpressed model CWQ group were lower than those of the corresponding NS groups， while the mRNA and protein expression levels of STAT3β and Bcl-2β were higher （P＜0.05 or P＜0.01）. All there groups of silenced model had lower subcutaneous tumor weight， Ki67 expression level， and mRNA and protein expression levels of PTBP3， STAT3α， and Bcl-2α in subcutaneous tumor tissue， as well as higher apoptosis level and mRNA and protein expression levels of STAT3β and Bcl-2β than those in all groups of control model； all groups of overexpressed model had higher subcutaneous tumor weight， Ki67 expression level， and mRNA and protein expression levels of PTBP3， STAT3α， and Bcl-2α ， while lower apoptosis level and mRNA and protein expression levels of STAT3β and Bcl-2β than those in all control model groups （P＜0.05 or P＜0.01）. In the control model， compared with the NS group， The tumor inhibition rate of all OXA groups was higher than that of corresponding CWQ groups， respectively. Compared to that of each control model group， the tumor inhibition rate was positive value of each silenced model group， and negative value of each overexpressed model group. ConclusionPTBP3 can promote the proliferation and inhibit apoptosis of intestinal cancer cells， upregulate the expression of STAT3α and Bcl-2α， and downregulate the expression of STAT3β and Bcl-2β in intestinal cancer cells. The meachnism of action of Changweiqing in the treatment of colorectal cancer maybe related to the inhibition of PTBP3， and regulation of the expression of STAT3α， STAT3β， Bcl-2α， and Bcl-2β.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the effect of exosomes loaded with Lycium barbarum miRNA(Lb-miR2911)on spermato-genic function recovery in non-obstructive azoospermia(NOA)rats through cross-regulation of the Wnt/β-catenin signaling pathways.Methods:We established an NOA model in 30 four-week-old male SD rats by intraperitoneal injection of busulfan.At 5 weeks after modeling,we equally randomized the rats into a model control group(MC,untreated),an Lb-miR2911EXO group(Lb-miR2911EXO,treated by intratesticular injection of Lb-miR2911-loaded exosomes),and a sham group(Shame,treated by intratesticular injection of exosomes-empty drug),with another 10 male SD rats taken as normal controls(NC).We observed the uptake and metabolic changes of Lb-miR2911 in the testis tissue of the rats by RNA FISH at 2 and 6 weeks after treatment,detected cell proliferation,spermatogenesis and gene expressions of the Wnt/β-catenin signaling pathways in the testis tissue by Transcriptome sequencing analysis combined with Western blot and RT-PCR at 12 weeks,evaluated the recovery of the spermatogenic function based on the testis tissue morphology and sperm quality,and assessed the organ toxicity of Lb-miR2911 in the tissue and organs of the rats based on histomorphological analysis and the levels of serum TNF-α,IL-1β,Aspartate aminotransferase(AST),Alanine aminotransferase(ALT)and other relevant indi-cators.Results:After 12 weeks of treatment,histomorphological analysis showed regular arrangement of spermatogenic cells at all levels in the testis tissue,with a large number of mature sperm in the tubular lumen,and with significantly higher Johnsen scores,tes-tis weight,testicular index,sperm concentration and sperm motility in the Lb-miR2911EXO than in the sham group(all P<0.05).Compared with the model controls,the Lb-miR2911EXO group exhibited remarkably down-regulated gene expression of DACT3(P<0.05),up-regulated expressions of DVL2 and β-catenin(P<0.05),elevated levels of p-DVL2 and β-catenin(nucleus)proteins(P<0.05),increased expressions of cell proliferation-related genes CCND1,CCNE1 and CCNE2(P<0.05)and spermatogenesis-related genes DMC1,CCR6,JAM2 and KLC3(P<0.05).No pathological changes were observed in the lung,liver and kidney tis-sues of the rats,or in the levels of serum TNF-α,IL-1β,AST,ALT,creatinine and urea nitrogen in the rats treated with Lb-miR2911EXO compared with the normal controls(P>0.05).Conclusion:Lb-miR2911-loaded exosomes promote spermatogenic function recovery in NOA rats through cross-regulation of the DACT3,Wnt and β-catenin signaling pathways.

Background and aim:Hepatic ischemia-reperfusion injury(IRI)is a significant challenge in liver trans-plantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors. Materials and methods:This study analyzed human liver and serum samples from five patients under-going the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results:Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating thera-peutic potential. Conclusions:Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

Objective:To investigate the role of long non-coding RNA LINC00261 in regulating E26 transcription factor 1(EST1)by interfering with the expression of miR-324-3p in promoting the development of gastric cancer(GC).Methods:Cancer tis-sues and corresponding adjacent normal tissues of GC patients(n=80)who underwent surgical treatment in 363 Hospital from June 2018 to October 2020 were collected as research samples,and the expression levels of LINC00261 and miR-324-3p were detected by qRT-PCR.The correlation between LINC00261 and clinicopathological parameters were analyzed.siRNA(si-LINC00261),miRNA mimic(miR-324-3p),miRNA inhibitor(miR-324-3p in)and their corresponding controls were transfected into MGC-803 and SGC-7901 cells.Clonogenesis assay was used to evaluate cell proliferation.The Transwell assay assessed cell migration and invasion.The protein expression levels of E-cadherin,N-cadherin and ETS1 were detected by Western blot.Tumor xenotransplantation assay was used to detect the tumorigenesis of LINC00261 in vivo.Luciferase report and RNA precipitation were used to analyze the interaction between LINC00261,miR-324-3p and EST1.Results:Compared with adjacent tissues,the expression of LINC00261 in GC tissues was significantly up-regulated with statistical significance(P<0.05).The expression of LINC00261 was correlated with TNM stage,tissue differentiation degree,lymph node metastasis and microvascular invasion(P<0.05).The database prediction,firefly luciferase assay and RNA immunoprecipitation results showed that LINC00261 had a targeted relationship with miR-324-3p.The level of miR-324-3p in GC tissues was significantly lower than that in paracellular normal tissues(P<0.05).There was a negative correlation between miR-324-3p level and LINC00261 expression(P<0.05).Compared with in NC+si-NC group,the cell proliferation,migration and invasion ability and the expression of N-cadherin in in NC+si-LINC00261 group were significantly inhibited(P<0.05),while the expression of E-cadherin was significantly increased(P<0.05).Compared with in NC+si-LINC00261 group,cell proliferation,migra-tion and invasion ability and expression of N-cadherin in si-LINC00261+miR-324-3p in group were significantly increased(P<0.05),while the expression of E-cadherin was significantly decreased(P<0.05).Targetscan prediction and firefly luciferase assay showed that ETS1 was the downstream binding site of miR-324-3p.After transfection with miR-324-3p,ETS1 protein level was significantly down-regulated(P<0.05),but after transfection with miR-324-3p in,ETS1 protein level was significantly up-regulated(P<0.05).The expression of ETS1 in GC tissue was significantly higher than that in adjacent normal tissue(P<0.05).The miR-324-3p level was negatively correlated with ETS1(P<0.05).The tumor weight of MGC-803 cells transfected with si-LINC00261 was lower than that of MGC-803 cells transfected with si-NC(P<0.05),and the protein level of ETS1 in si-LINC00261-derived tumors was lower than that of si-NC tumors(P<0.05).Conclusion:LINC00261 is highly expressed in GC tissue,which may affect EST1 expression and promote GC progress by regulating miR-324-3p.