BACKGROUND:In the initial stage of growth plate injury inflammation,platelet-derived growth factor BB promotes the repair of growth plate injury by promoting mesenchymal progenitor cell infiltration,chondrogenesis,osteogenic response,and regulating bone remodeling. OBJECTIVE:To elucidate the action mechanism of platelet-derived growth factor BB after growth plate injury. METHODS:PubMed,VIP,WanFang,and CNKI databases were used as the literature sources.The search terms were"growth plate injury,bone bridge,platelet-derived growth factor BB,repair"in English and Chinese.Finally,66 articles were screened for this review. RESULTS AND CONCLUSION:Growth plate injury experienced early inflammation,vascular reconstruction,fibroossification,structural remodeling and other pathological processes,accompanied by the crosstalk of chondrocytes,vascular endothelial cells,stem cells,osteoblasts,osteoclasts and other cells.Platelet-derived growth factor BB,as an important factor in the early inflammatory response of injury,regulates the injury repair process by mediating a variety of cellular inflammatory responses.Targeting the inflammatory stimulation mediated by platelet-derived growth factor BB may delay the bone bridge formation process by improving the functional activities of osteoclasts,osteoblasts,and chondrocytes,so as to achieve the injury repair of growth plate.Platelet-derived growth factor BB plays an important role in angiogenesis and bone repair tissue formation at the injured site of growth plate and intrachondral bone lengthening function of uninjured growth plate.Inhibition of the coupling effect between angiogenesis initiated by platelet-derived growth factor BB and intrachondral bone formation may achieve the repair of growth plate injury.

ObjectiveTo observe the effect of Shenshu Fujian decoction on platelet-derived growth factor （PDGF）/naked cuticle homolog 2 （NKD2） /Wnt signaling pathway in rats with chronic renal failure （CRF）. MethodsSixty male SD rats were randomly divided into normal group， model group， Niaoduqing group （5 g·kg^-1）， low-dose Shenshu Fujian decoction group （5.5 g·kg^-1）， medium-dose Shenshu Fujian decoction group （11 g·kg^-1）， and high-dose Shenshu Fujian decoction group （22 g·kg^-1）， with 10 rats in each group. A CRF rat model was established by feeding a 0.5% adenine diet for 21 days. After successful modeling， intragastric administration was given once daily for 28 consecutive days. After treatment， the renal morphology of rats was observed. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected. Hematoxylin-eosin （HE） staining and Masson staining were used to detect renal histopathological changes， and collagen volume fraction （CVF） was calculated. Serum levels of inflammatory markers interleukin （IL）-1β and IL-6 were measured using enzyme-linked immunosorbent assay （ELISA）. The expressions of fibronectin 1 （FN1）， type Ⅰ collagen （ColⅠ）， α-smooth muscle actin （α-SMA）， platelet-derived growth factor receptor-β （PDGFR-β）， NKD2， dishevelled protein 2 （DVL2） and β-catenin in renal tissue were detected by immunohistochemistry and Western blot. ResultsCompared with the normal group， the model group showed significant renal pathological changes， a markedly increased kidney weight/body weight ratio （P<0.01）， significantly elevated CVF （P<0.01）， and notably increased serum levels of SCr， BUN， IL-1β， and IL-6 （P<0.01）. Expression levels of FN1， ColⅠ， α-SMA， PDGFR-β， NKD2， DVL2， and β-catenin in renal tissue were also significantly increased （P<0.01）. Compared with the model group， all treatment groups showed significantly decreased kidney weight/body weight ratios and CVF （P<0.01）， as well as markedly decreased serum SCr， BUN， IL-1β， and IL-6 levels. Protein expression levels of FN1， ColⅠ， α-SMA， PDGFR-β， NKD2， DVL2， and β-catenin in renal tissue were decreased， with more pronounced effects observed in the Niaoduqing， medium-dose， and high-dose Shenshu Fujian decoction groups （P<0.05， P<0.01）. ConclusionShenshu Fujian decoction improves renal function， reduces inflammation， and reverses renal fibrosis in CRF rats， possibly by downregulating the expression of PDGF/NKD2/Wnt signaling pathway-related proteins.

ObjectiveTo observe the effects of Hirudo， Notoginseng Radix et Rhizoma， and drug pair on renal pathological morphology and protein phosphatase 2A （PP2A）/adenylate activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signal pathway in rats with chronic renal failure （CRF）. MethodThe 55 male SD rats were randomly divided into a normal group （n=11） and a modeling group （n=44）. The normal group was fed conventionally， and the modeling group was given 0.25 g·kg^-1·d^-1 adenine by gavage for 28 days to replicate the CRF model. After successful modeling， rats were randomly divided into model group， Hirudo group （3 g·kg^-1·d^-1）， Notoginseng Radix et Rhizoma group （3 g·kg^-1·d^-1）， and Hirudo + Notoginseng Radix et Rhizoma group （3 g·kg^-1·d^-1）， with 9 rats in each group. The normal group and model group were given a constant volume of normal saline by intragastric administration for 30 days. At the end of the experiment， the levels of serum creatinine （SCr） and urea nitrogen （BUN） in all groups were measured. The renal pathological morphology changes were observed by hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy. The mRNA expressions of PP2A， AMPK， and mTOR were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of PP2A， AMPK， phosphorylation（p）-AMPK， mTOR， and p-mTOR in renal tissue were detected by Western blot. ResultCompared with the normal group， the renal pathological structure changes were obvious， and the levels of SCr and BUN were significantly increased. The mRNA expression of PP2A， protein expression of PP2A， and p-mTOR/mTOR expression were significantly increased， and the p-AMPK/AMPK was significantly decreased in the model group （P<0.05）. Compared with the model group， the renal pathological morphology changes were significantly improved， and the levels of SCr and BUN were significantly decreased. The mRNA expression of PP2A， protein expression of PP2A， and p-mTOR/mTOR expression in the renal tissue were significantly decreased， and the p-AMPK/AMPK was significantly increased （P<0.05） in all groups after drug intervention. In addition， the effect in the Hirudo+Notoginseng Radix et Rhizoma group was better. The mRNA expression levels of AMPK and mTOR in the renal tissue were not significantly different among the normal group， model group， and other groups. ConclusionThe efficacy of Hirudo and Notoginseng Radix et Rhizoma pairs in improving renal fibrosis in rats with CRF is significantly better than that of the single drug， and its improvement on renal fibrosis in rats with CRF may be related to the regulation of PP2A/AMPK/mTOR signaling pathway.

Objective To assess inter-observer variations(IOV)in the delineation of target volumes and organs-at-risk(OAR)for intensity-modulated radiotherapy(IMRT)of nasopharyngeal carcinoma(NPC)among physicians from different levels of cancer centers,thereby providing a reference for quality control in multi-center clinical trials.Methods Twelve patients with NPC of different TMN stages were randomly selected.Three physicians from the same municipal cancer center manually delineated the target volume(GTVnx)and OAR for each patient.The manually modified and confirmed target volume(GTVnx)and OAR delineation structures by radiotherapy experts from the regional cancer center were used as the standard delineation.The absolute volume difference ratio(△V_diff),maximum/minimum volume ratio(MMR),coefficient of variation(CV),and Dice similarity coefficient(DSC)were used to compare the differences in organ delineation among physicians from different levels of cancer centers and among the 3 physicians from the same municipal cancer center.Furthermore,the IOV of GTVnx and OAR among physicians from different levels cancer centers were compared across different TMN stages.Results Significant differences in the delineation of GTVnx were observed among physicians from different levels of cancer centers.Among the 3 physicians,the maximum values of △V_diff,MMR,and CV were 97.23%±83.45%,2.19±0.75,and 0.31±0.14,respectively,with an average DSC of less than 0.7.Additionally,there were considerable differences in the delineation of small-volume OAR such as the left and right optic nerves,chiasm,and pituitary,with average MMR>2.8,CV>0.37,and DSC<0.51.However,relatively smaller differences were observed in the delineation of large-volume OAR such as the brainstem,spinal cord,left and right eyeballs,and left and right mandible,with average△V_diff<42%,MMR<1.55,and DSC>0.7.Compared with the differences among physicians from different levels cancer centers,the differences among the 3 physicians from the municipal cancer center were slightly reduced.Furthermore,there were also differences in the delineation of target volumes for NPC among physicians from different levels cancer centers,depending on the staging of the disease.Compared with the delineation of target volumes for earlier stage patients(stages I or II),the differences among physicians in the delineation of target volumes for advanced stage patients(stages III or IV)were smaller,with average △V_diff and DSC of 98.31%±67.36%vs 69.38%±72.61%(P<0.05)and 0.55±0.08 vs 0.72±0.12(P<0.05),respectively.Conclusion There are differences in the delineation of GTVnx and OAR in radiation therapy for NPC among physicians from different levels of cancer centers,especially in the delineation of target volume(GTVnx)and small-volume OAR for early-stage patients.To ensure the accuracy of multicenter clinical trials,it is recommended to provide unified training to physicians from different levels of cancer centers and review their delineation results to reduce the effect of differences on treatment outcomes.

Objective To investigate the effect of dapagliflozin on myocardial work and energy metabolism in patients with heart failure with reduced ejection fraction(HFrEF)without type 2 diabetes mellitus(T2DM).Methods Patients with HFrEF without T2DM who visited Wuzhou People's Hospital from January 2021 to January 2022 were randomly divided into conventional group and dapagliflozin group(conventional treatment+dapagliflozin).After treatment(12 months),myocardial work[global work index(GWI),global constructed work(GCW),global wasted work(GW),and global work efficiency(GWE)],energy metabolism[(free fatty acids(FFA)and β-hydroxybutyric acid(β-HB)],traditional cardiac function[left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and left ventricular ejection fraction(LVEF)],clinical efficacy,prognosis[mortality,rehospitalization,and incidence of major adverse cardiovascular events(MACE)]and adverse reactions were compared between the two groups.Results A total of 128 patients with HFrEF without T2DM were enrolled,including 63 patients in the dapagliflozin group and 65 patients in the conventional group.After treatment,the LVEDD,LVESD,GWW,NT-pro BNP in the dapagliflozin group was significantly lower than that in the conventional group(P＜0.05),while the LVEF,GWI,GCW,GWE,β-HB acid and FFA were significantly higher than those in the conventional group(P＜0.05).The total effective rate and hypoglycemia rates in the dapagliflozin group were significantly higher than those in the conventional group(P＜0.05),and the rehospitalization rate and MACE rate were significantly lower than those in the conventional group(P＜0.05).There were no significant differences in mortality,renal adverse events,urinary tract infections and gastrointestinal symptoms between the two groups(P＞0.05).Conclusion Dapagliflozin has significant clinical efficacy in patients with HFrEF without T2DM,which can increase the serum levels of FFA and ketones,improve effective work,and reduce ineffective work,but it is necessary to be vigilant against hypoglycemia.

Objective To evaluate the quality of treatment planning(TP)and re-optimization planning(RP)of radiotherapy for rectal cancer using PlanIQ software,thereby providing methods and tools for the screening and optimization of radiotherapy plans.Methods Twenty patients with rectal cancer who received radiotherapy were selected retrospectively,with 10 cases of intensity-modulated radiotherapy(IMRT)and 10 of volumetric modulated arc therapy(VMAT).(1)TP:IMRT plan involved 5-field irradiation,and VMAT plan involved two 360°arcs.The prescription doses were 50 Gy/25 f for PTV1 and 45 Gy/25 f for PTV2.All plans underwent direct machine parameter optimization and required 95%isodose lines to cover 100%of the target volume.Organs-at-risk(OAR)were limited by reference to tolerated dose standards.After the planning was completed,the plans were reviewed and confirmed by a physician,and the treatment was implemented after dose verification.(2)RP:a physicist with 10 years of experience re-optimized the 20 TP plans,with the irradiation technique and field setting unchanged.The re-optimization involved adjusting planning conditions and parameters based on individual experience until the dose to OAR was minimized while without affecting PTV coverage.The quality of TP plans and RP plans were quantitatively evaluated using PlanIQ software.Non-parametric Wilcoxon signed rank test was performed for dose-volume histogram parameters and plan quality index between two groups.Results The dose-volume histogram parameters in RP plans were superior to those in TP plans,and the differences in the Dmax of PTV1,the V45 Gy and Dmax of small intestine,and the V45 Gy of colon were statistically significant(P<0.05).The quality scores of RP plans for IMRT group,VMAT group and all patients were significantly higher than those of TP plans(P<0.05),with plan quality index of 88.55±3.35 vs 86.61±4.63(P=0.005),89.72±3.15 vs 87.21±3.04(P=0.028),and 89.14±3.22 vs 86.91±3.22(P=0.001),respectively.Conclusion RP can further improve the quality of radiotherapy plan for rectal cancer.PlanIQ software serves as an effective tool for quality control and screening of radiotherapy planning.

Objective: To explore the mechanism by which icariin alleviates viral myocarditis. Methods: CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability, inflammation, and apoptosis. Moreover, the effects of icariin on ferroptosis and TLR4 signaling were assessed. After AC16 cells were transfected with TLR4 overexpression plasmids, the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated. Results: Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α, IL-1β, IL-6, and IL-18. Flow cytometry revealed that icariin decreased apoptosis rate, and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes. Additionally, it suppressed ferroptosis including lipid peroxidation and ferrous ion, as well as the TLR4 signaling. However, TLR4 overexpression abrogated the modulatory effects of icariin. Conclusions: Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis. Further animal study is needed to verify its efficacy.

Objective:To investigate the genetic and evolutionary characteristics of hemagglutinin (HA) and neuraminidase (NA) genes of influenza B/Victoria (BV) virus in Xi′an city from 2019 to 2023.Methods:Twenty-five BV strains isolated from the Xi′an influenza surveillance network laboratory between 2019 and 2023 were collected. The HA and NA genes were sequenced using MiniSeq high-throughput sequencing platform. An evolutionary tree was constructed using bioinformatics software to analyze homology and mutation sites, and to predict N-glycosylation sites online. The antigenicity of the strains was analyzed through hemagglutination inhibition tests.Results:The BV influenza in Xi′an exhibited a distinct seasonal transmission pattern from 2019 to 2023, with peak prevalence occurring during the winter and spring seasons. The evolutionary analysis of the HA genes shows that the strains from Xi′an in 2019 belong to the V1A.3 branch, and the strains from 2021 to 2023 belong to the V1A.3a.2 branch. Analysis of antigenic sites showed that there were variations in 6 sites of 3 antigenic determinants in the HA proteins of the BV strains from 2021-2022 compared to 2019, and 2 sites of 1 antigenic determinant changed in the HA proteins in 2023 compared to 2021-2022. The evolutionary analysis of the NA genes indicates that the BV strains from Xi′an in 2019 belong to the A. 1.1 branch. By 2021 and 2022, it had evolved into the A. 1.2 clade, and by 2023, it had further evolved into the B clade and its derivatives, with no strains showing mutations associated with resistance to NA inhibitors. Antigenic analysis indicated that the majority of BV strains in Xi′an were similar to the strains included in the vaccine composition. Furthermore, glycosylation analysis showed that the potential N-glycosylation sites in the HA proteins of BV strains from 2021-2023 were reduced by one compared to those from 2019, and only a few strains from 2023 displayed alterations in the potential N-glycosylation sites of the NA proteins.Conclusions:The HA and NA genes of the BV strains from 2019 to 2023 are continuously mutating and evolving into new branches. Since 2021, V1A.3a.2 has become the dominant evolutionary branch of the HA genes, while the evolutionary branches of the NA genes from 2019 to 2023 have been continuously changing.

Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary site.However,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune microenvironment.This study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma. Methods:Anoikis-related genes(ANRGs)were obtained from GeneCards.Clinical information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)databases.ANRGs highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)algorithm.Machine learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO cohort.Finally,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor microenvironment. Results:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic model.Significant differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling pathway. Conclusion:The prognostic model based on ANRGs and tumor microenvironment demonstrate good predictive power and provide more personalized treatment options for patients with osteosarcoma.

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.