Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

Background:Ribosomal protein L22-like 1(RPL22L1)exerts regulatory effects on various malignant tumors such as lung cancer,prostate cancer,and cervical cancer.However,its role in colorectal cancer(CRC)remains unclear.Aims:To investigate the expression of RPL22L1 in CRC and its role in patients' prognosis and glucose metabolism of tumor cells.Methods:A total of 142 newly diagnosed CRC patients admitted to the Taizhou First People's Hospital from February 2022 to June 2024 were enrolled.The expression levels of RPL22L1 mRNA and protein were detected by quantitative real-time PCR and immunohistochemistry,respectively.The correlation between RPL22L1 expression and clinicopathological characteristics was analyzed.Kaplan-Meier survival analysis was used to evaluate the impact of RPL22L1 expression on the prognosis of CRC patients.RPL22L1 siRNA was transfected into SW480 cells to establish a low-expression cell model.Cell proliferation was assessed by CCK-8 assay,cell migration by Transwell chamber assay,and apoptosis by flow cytometry.Gene set enrichment analysis(GSEA)was performed to evaluate the effect of RPL22L1 on glucose metabolism of tumor cells.Results:The expression levels of RPL22L1 mRNA and protein were significantly higher in CRC tissues than in adjacent normal tissues(all P<0.05).The expression level of RPL22L1 mRNA was correlated with the TNM stage and carcinoembryonic antigen level of CRC(all P<0.05).Kaplan-Meier analysis showed that the cumulative survival rate of high RPL22L1 mRNA expression group was significantly lower than that of low-expression group(P=0.027).The expression level of RPL22L1 mRNA was significantly higher in SW480 cells than in normal intestinal epithelial cells(P<0.001).After inhibiting RPL22L1 expression,the proliferation and migration capacities of SW480 cells were significantly decreased(all P<0.05),the apoptosis rate was significantly increased(P=0.005),and the lactate level and relative glucose uptake level were significantly reduced(all P<0.05).GSEA indicated that RPL22L1 gene was associated with glycolysis/gluconeo-genesis(P=0.02).Conclusions:RPL22L1 is highly expressed in CRC and is associated with poor prognosis of patients,suggesting its potential as a molecular target for CRC therapy.Furthermore,RPL22L1 may promote the tumorigenesis and progression of CRC by modulating glucose metabolism.

OBJECTIVE To evaluate the quality of diagnosis and treatment guidelines and expert consensuses on childhood immune thrombocytopenic purpura(ITP)published domestically and internationally,in order to provide reference for clinical practice and future guideline/expert consensus development and improvement.METHODS A systematic search was conducted across multiple databases,including PubMed,Cochrane Library,Embase,CNKI,Wanfang data,VIP,CBM;additionally,supplementary searches were carried out on websites such as Medlive,the Chinese Medical Association's official website,and National Institute for Health and Clinical Excellence in the UK.The retrieval time ranged from the inception to September 2,2024.Researchers who had undergone systematic training independently evaluated the methodology and report quality included in the guideline/consensus using the Appraisal of Guidelines Research and Evaluation Ⅱ(AGREE Ⅱ)and the Reporting Items for Practice Guidelines in Healthcare(RIGHT).RESULTS A total of 11 guidelines/consensuses were included.The average scores for the six domains of AGREE Ⅱ tool respectively were"range and purpose"[(66.67±17.98)%],"participants"[58.33%(13.89%,73.61%)],"rigor"[(41.81±23.85)%],"clarity"[(69.57±19.35)%],"applicability"[(35.98±17.83)%],and"independence"[27.08%(0,75.00%)];out of 11 articles,9 had a recommendation level of B,2 had a recommendation level of C,and there were no A-level articles.The average reporting rates of the 7 areas in the RIGHT tool were"basic information"[(72.35±12.95)%],"background"[(54.55±15.40)%],"evidence"[(36.36±24.81)%],"recommended opinions"[(53.25±19.20)%],"review and quality assurance"[0(0,25.00%)],"funding and conflict of interest statement and management"[12.50%(0,25.00%)],and other aspects[8.33%(0,50.00%)].In addition,there was no statistically significant difference in the AGREE Ⅱ and RIGHT scores between the guidelines and consensuses(P＞0.05).CONCLUSIONS The overall quality of the guidelines and consensuses included in this study is not high,with a recommended level of B or C.It is recommended that clinical decision-making prioritize referring to the relatively high-quality guideline/consensus among them.The quality of evidence in the existing traditional Chinese medicine guidelines for children with ITP needs to be improved,and there is no integrated guideline/consensus for traditional Chinese and Western medicine.It is recommended to revise or write relevant guideline/consensus according to the requirements of AGREE Ⅱ and RIGHT in various fields to guide clinical practice.

OBJECTIVE To optimize the stir-frying process of Platycodon grandiflorum,compare the protective effect of P.grandiflorum on lung injury in mice before and after stir-frying,and preliminarily explore the characteristics of"enhanced efficacy through processing"of stir-frying P.grandiflorum.METHODS On the basis of single-factor experiment,the stir-frying time,temperature and frequency were taken as factors,and the comprehensive scores of appearance traits,platycodin D content and alcohol extract content were taken as indexes.Box-Behnken response surface experiment was designed to optimize the stir-frying process of P.grandiflorum and verify it.The mice were divided into blank control group,model group,dexamethasone group(positive control drug,5 mg/kg),P.grandiflorum low-dose and high-dose groups(0.6,1.2 g/kg),fried P.grandiflorum low and high dose groups(0.6,1.2 g/kg),with 8 mice in each group.The treatment was given once a day for 10 consecutive days.After the last administration,acute lung injury model was established by intratracheal instillation of lipopolysaccharide.The levels of interleukin-6(IL-6),IL-1β,tumor necrosis factor-α(TNF-α)in serum and superoxide dismutase(SOD),myeloperoxidase(MPO)and malondialdehyde(MDA)in lung tissue were detected,lung wet/dry weight ratio and thymus index were calculated,and the pathological changes of lung tissue were observed.RESULTS The optimum processing conditions were as follows:stir-frying temperature of 120℃,stir-frying time of 12 min,stir-frying frequency of 19 r/min;the comprehensive scores of the three batches of process verification were all greater than 97 points,RSD＜3%(n=3).The results of pharmacodynamic experiments showed that compared with blank control group,the lung dry-wet weight ratio as well as the levels of IL-6,IL-1β,TNF-α,MPO and MDA in the model group were significantly increased(P＜0.01),the thymus index and SOD level were significantly decreased(P＜0.01),and the lung tissue was significantly damaged.Compared with model group,above indexes of the mice in each administration group were significantly improved(P＜0.01),and the lung tissue injury was significantly reduced.At the same dose,except for the lung dry-wet weight ratio,the above indexes of the mice in the stir-fried P.grandiflorum groups were significantly improved compared with P.grandiflorum groups(P＜0.05),and the lung tissue damage was further reduced.CONCLUSIONS The optimized stir-frying process is stable and feasible.The protective effect of stir-fried P.grandiflorum on acute lung injury in mice is better than that of raw products at the same dosage.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To investigate the anti-fatigue effect of Dendrobium and Panax Quinquefolius Granules(DPQG)on the overtrained mice,and to clarify its possible mechanism.Methods:A total of 48 mice were randomly divided into control group(equal volume of distilled water),low dose of DPQG group(400 mg·kg-1 DPQG),medium dose of DPQG group(800 mg·kg-1 DPQG),and high dose of DPQG group(1 600 mg·kg-1 DPQG).The DPQG were administered by gavage for 35 d,and the rotarod test and swimming endurance test were performed 30 min after last administration.Serum,liver tissue,and muscle tissue were collected from the mice in various groups.ELISA method was used to detect the serum lacticacid(LAC)levels and lactate dehydrogenase(LDH)activities,and the malondialdehyde(MDA)levels,superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)activities,and the liver glycogen and muscle glycogen levels in muscle tissue of the mice in various groups;HE staining was used to observe the pathomorphology of muscle tissue of the mice.Transcriptomics and metabolomics technologies were used to identify the key genes and metabolites in muscle tissue of the mice in control group and high dose of DPQG group and to analyze the correlations between differentially expressed genes(DEGs)and differentially expressed metabolites.Results:Compared with control group,the rod turning exhaustion time of the mice in different doses of DPQG groups were significantly increased(P＜0.05),and the swimming exhaution time of the mice in high dose of DPQG group was increased(P＜0.05).Compared with control group,the LDH,SOD,and GSH-Px activities of the mice in medium and high doses of DPQG groups were increased(P＜0.01).Compared with control group,the levels of MDA and liver glycogen of the mice in medium and high doses of DPQG groups were decreased(P＜0.05 or P＜0.01).The transcriptomics sequencing results showed that DPQG mainly acted on DEGs such as Trib3 and Olfr495;the Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis results showed that the DEGs were mainly enriched in olfactory-related processes and signaling pathways;the metabolomics KEGG analysis results showed that the differential metabolites were mainly enriched in the regulation pathway of inflammatory mediators on tryptophan(TRP);the combined analysis of transcriptomics and metabolomics results showed that the piezo1 gene had high correlations with the differential metabolites β1-solamarine(r=-1,P＜0.05)and tilidine(r=1,P＜0.05).Conclusion:DPQG can exert an anti-fatigue effect on the overtrained mice by modulating LAC metabolism and glycogen homeostasis,as well as maintaining the oxidative/antioxidant balance in the body;its anti-fatigue mechanism is related to the Olfr495 and piezo1 genes and the regulation pathway of inflammatory mediators on TRP channels.

Background:Ribosomal protein L22-like 1(RPL22L1)exerts regulatory effects on various malignant tumors such as lung cancer,prostate cancer,and cervical cancer.However,its role in colorectal cancer(CRC)remains unclear.Aims:To investigate the expression of RPL22L1 in CRC and its role in patients' prognosis and glucose metabolism of tumor cells.Methods:A total of 142 newly diagnosed CRC patients admitted to the Taizhou First People's Hospital from February 2022 to June 2024 were enrolled.The expression levels of RPL22L1 mRNA and protein were detected by quantitative real-time PCR and immunohistochemistry,respectively.The correlation between RPL22L1 expression and clinicopathological characteristics was analyzed.Kaplan-Meier survival analysis was used to evaluate the impact of RPL22L1 expression on the prognosis of CRC patients.RPL22L1 siRNA was transfected into SW480 cells to establish a low-expression cell model.Cell proliferation was assessed by CCK-8 assay,cell migration by Transwell chamber assay,and apoptosis by flow cytometry.Gene set enrichment analysis(GSEA)was performed to evaluate the effect of RPL22L1 on glucose metabolism of tumor cells.Results:The expression levels of RPL22L1 mRNA and protein were significantly higher in CRC tissues than in adjacent normal tissues(all P<0.05).The expression level of RPL22L1 mRNA was correlated with the TNM stage and carcinoembryonic antigen level of CRC(all P<0.05).Kaplan-Meier analysis showed that the cumulative survival rate of high RPL22L1 mRNA expression group was significantly lower than that of low-expression group(P=0.027).The expression level of RPL22L1 mRNA was significantly higher in SW480 cells than in normal intestinal epithelial cells(P<0.001).After inhibiting RPL22L1 expression,the proliferation and migration capacities of SW480 cells were significantly decreased(all P<0.05),the apoptosis rate was significantly increased(P=0.005),and the lactate level and relative glucose uptake level were significantly reduced(all P<0.05).GSEA indicated that RPL22L1 gene was associated with glycolysis/gluconeo-genesis(P=0.02).Conclusions:RPL22L1 is highly expressed in CRC and is associated with poor prognosis of patients,suggesting its potential as a molecular target for CRC therapy.Furthermore,RPL22L1 may promote the tumorigenesis and progression of CRC by modulating glucose metabolism.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To investigate whether Lycium barbarum polysaccharides(LBP)can inhibit ferroptosis through the solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4)pathway and thus alleviate cerebral ischemia-reperfusion(I/R)injury.Methods:The mouse model of cerebral I/R injury was established by mid-dle cerebral artery occlusion(MCAO)and treated with Lycium barbarum polysaccharides(LBP).The mice were ran-domly divided into three groups:sham group,I/R group,and I/R+LBP group.2,3,5triphenyltetrazolium chloride(TTC)staining was used to observe the volume of cerebral infarcts;Neurological function was assessed by neurological deficit score;The superoxide dismutase(SOD),glutathione(GSH),malondialdehyde(MDA),and Fe2+detection kit to detect the changing levels of SOD,GSH,MDA,and Fe2+;Western Blot detects the expression of ferroptosis-related keys GPX4,SLC7A11,and Nrf2.Results:LBP can reduce the cerebral infarction volume and improve the neurological function.LBP increases the content of SOD and GSH and reduces the content of MDA in I/R injured mice.Western Blot results show that the expression levels of ferroptosis-related proteins GPX4,SLC7A11,and Nrf2 in the brain tissue of the I/R group were significantly lower than those of the Sham group.After LBP treatment,the levels of GPX4,SLC7A11,and Nrf2 in the LBP+I/R group were significantly higher than those of the I/R group.Conclusion:LBP at-tenuates cerebral I/R injury by inhibiting ferroptosis through the SLC7A11/GPX4 pathway.LBP has a neuroprotective effect on cerebral I/R injury and is a potential neuroprotective agent.

Objective To explore the value of Chinese thyroid imaging reporting and data system(C-TIRADS)combined with intranodular and perinodular stiffness for distinguishing benign and malignant thyroid nodules.Methods Data of routine ultrasound and ultrasonic shear wave elastography(SWE)in 117 patients with thyroid nodules confirmed by fine needle aspiration cytology(FNAC)and/or surgical pathology were retrospectively analyzed.The nodules were classified according to C-TIRADS and SWE parameters of nodules and surrounding 2 mm glands measured with SWE technique,including Young's modulus of thyroid nodules(E)and perinodular glandular(Eshell)(the maximum[Emax/Eshellmax],the mean[Emean/Eshellmean]and the minimum[Emin/Eshellmin]as well as standard deviation[ESD/EshellSD]values).Then receiver operating characteristic(ROC)curve was drawn,and area under the curve(AUC)was calculated to assess the efficacy of C-TIRADS,SWE and the combination for differentiating benign and malignant thyroid nodules.Results Totally 117 thyroid nodules of 117 patients were enrolled,including 50 benign and 67 malignant ones.SWE parameters of malignant thyroid nodules were higher than those of benign ones(all P＜0.001).AUC of C-TIRADS for differentiating benign and malignant thyroid nodules was 0.736,with sensitivity of 79.10％,specificity of 68.00％and accuracy of 74.36％.AUC of Emax,Emean,Emin and ESD was 0.816,0.752,0.664 and 0.705,respectively,of Emax was the highest.AUC of Eshellmax,Eshellmean,Eshellmin and EshellSD was 0.834,0.804,0.693 and 0.697,respectively,of Eshellmax was the highest,which was not statistically difference with that of Emax(Z=1.044,P=0.297).AUC of C-TIRADS+Emax and C-TIRADS+Eshellmax was 0.835 and 0.843,respectively,being not significantly different(Z=0.574,P=0.566)but higher than that of C-TIRADS(AUC=0.736,Z=2.510,2.230,both P＜0.05),with diagnostic specificity and accuracy both higher than those of C-TIRADS(all P＜0.05).Conclusion C-TIRADS combined with intranodular and perinodular stiffness could be used to effectively distinguish benign and malignant thyroid nodules,which might improve diagnostic efficiency of C-TIRDAS.