BACKGROUND:Bone tissue loss caused by tumors and trauma can have an adverse effect on postoperative rehabilitation.Therefore,scaffold materials are usually implanted during treatment.However,the existing implant materials are relatively simple and lack antibacterial properties.Early implantation may lead to iatrogenic autoinfection and have an adverse effect on osteogenesis.OBJECTIVE:To construct a KR-12-a5 polypeptide-nanohydroxyapatite-small intestinal submucosa composite scaffold and evaluate its feasibility as a material for promoting bone defect repair.METHODS:The small intestinal submucosa scaffold and the small intestinal submucosa scaffold containing 25,50,and 100 mg/mL nanohydroxyapatite(referred to as nHA-SIS scaffold)were prepared by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide cross-linking method.The appropriate scaffold was screened for subsequent experiments by mechanical property testing.The antibacterial properties of KR-12-a5 polypeptide solution against Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum were detected.The nHA-SIS scaffolds were immersed in 250,500,and 1 000 μg/mL KR-12-a5 peptide solutions for 24 hours,and then freeze-dried to obtain peptide-loaded nanohydroxyapatite-porcine small intestinal submucosa composite scaffolds(denoted as P-nHA-SIS scaffolds).The sustained-release properties of the three groups of scaffolds were characterized.The nHA-SIS scaffolds and the three groups of P-nHA-SIS scaffolds were co-cultured with Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum for 24 hours or 48 hours.The scaffolds with strong antibacterial ability were screened by live and dead bacteria staining and scanning electron microscopy for subsequent experiments.The degradation properties and water absorption rates of the uncross-linked small intestinal submucosa scaffolds,cross-linked small intestinal submucosa scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were characterized.The extracts of cross-linked small intestinal submucosal scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were co-cultured with MC3T3-E1 cells.CCK-8 assay and live-dead cell staining were performed.The effects of the extracts of the three scaffolds on the migration of MC3T3-E1 cells were detected by Transwell chamber assay.RESULTS AND CONCLUSION:(1)The elastic modulus and compressive strength of 25,50,and 100 mg/mL nHA-SIS scaffolds were higher than those of small intestinal submucosal scaffolds(P＜0.05),among which the elastic modulus and compressive strength of 25 mg/mL nHA-SIS scaffolds were the highest,and this group of scaffolds were selected for subsequent experiments to load peptides.(2)KR-12-a5 peptide had strong antibacterial activity against common bacteria in bone defects(Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum).The three groups of P-nHA-SIS scaffolds all had sustained release properties.With the increase of peptide mass concentration,the antibacterial property of P-nHA-SIS scaffold was enhanced.Among them,the P-nHA-SIS scaffold loaded with 500 μg/mL peptide had achieved a satisfactory antibacterial effect,and this group of scaffolds would be selected in the future.(3)The degradation rate of the three groups of cross-linked scaffolds was lower than that of the uncross-linked scaffolds,and the water absorption rate was greater than that of the uncross-linked scaffolds.P-nHA-SIS scaffolds could promote the proliferation and migration of MC3T3-E1 cells without affecting the activity of MC3T3-E1 cells.(4)The results show that P-nHA-SIS scaffolds have strong antibacterial properties and the ability to promote the proliferation and migration of MC3T3-E1 cells,and are expected to be used in bone defect repair.

BACKGROUND:Bone tissue loss caused by tumors and trauma can have an adverse effect on postoperative rehabilitation.Therefore,scaffold materials are usually implanted during treatment.However,the existing implant materials are relatively simple and lack antibacterial properties.Early implantation may lead to iatrogenic autoinfection and have an adverse effect on osteogenesis.OBJECTIVE:To construct a KR-12-a5 polypeptide-nanohydroxyapatite-small intestinal submucosa composite scaffold and evaluate its feasibility as a material for promoting bone defect repair.METHODS:The small intestinal submucosa scaffold and the small intestinal submucosa scaffold containing 25,50,and 100 mg/mL nanohydroxyapatite(referred to as nHA-SIS scaffold)were prepared by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide cross-linking method.The appropriate scaffold was screened for subsequent experiments by mechanical property testing.The antibacterial properties of KR-12-a5 polypeptide solution against Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum were detected.The nHA-SIS scaffolds were immersed in 250,500,and 1 000 μg/mL KR-12-a5 peptide solutions for 24 hours,and then freeze-dried to obtain peptide-loaded nanohydroxyapatite-porcine small intestinal submucosa composite scaffolds(denoted as P-nHA-SIS scaffolds).The sustained-release properties of the three groups of scaffolds were characterized.The nHA-SIS scaffolds and the three groups of P-nHA-SIS scaffolds were co-cultured with Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum for 24 hours or 48 hours.The scaffolds with strong antibacterial ability were screened by live and dead bacteria staining and scanning electron microscopy for subsequent experiments.The degradation properties and water absorption rates of the uncross-linked small intestinal submucosa scaffolds,cross-linked small intestinal submucosa scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were characterized.The extracts of cross-linked small intestinal submucosal scaffolds,nHA-SIS scaffolds,and P-nHA-SIS scaffolds were co-cultured with MC3T3-E1 cells.CCK-8 assay and live-dead cell staining were performed.The effects of the extracts of the three scaffolds on the migration of MC3T3-E1 cells were detected by Transwell chamber assay.RESULTS AND CONCLUSION:(1)The elastic modulus and compressive strength of 25,50,and 100 mg/mL nHA-SIS scaffolds were higher than those of small intestinal submucosal scaffolds(P＜0.05),among which the elastic modulus and compressive strength of 25 mg/mL nHA-SIS scaffolds were the highest,and this group of scaffolds were selected for subsequent experiments to load peptides.(2)KR-12-a5 peptide had strong antibacterial activity against common bacteria in bone defects(Staphylococcus aureus,Streptococcus gordonii,and Fusobacterium nucleatum).The three groups of P-nHA-SIS scaffolds all had sustained release properties.With the increase of peptide mass concentration,the antibacterial property of P-nHA-SIS scaffold was enhanced.Among them,the P-nHA-SIS scaffold loaded with 500 μg/mL peptide had achieved a satisfactory antibacterial effect,and this group of scaffolds would be selected in the future.(3)The degradation rate of the three groups of cross-linked scaffolds was lower than that of the uncross-linked scaffolds,and the water absorption rate was greater than that of the uncross-linked scaffolds.P-nHA-SIS scaffolds could promote the proliferation and migration of MC3T3-E1 cells without affecting the activity of MC3T3-E1 cells.(4)The results show that P-nHA-SIS scaffolds have strong antibacterial properties and the ability to promote the proliferation and migration of MC3T3-E1 cells,and are expected to be used in bone defect repair.

ObjectiveTo compare the Children's Hepatic tumors International Collaboration （CHIC） and the new Chinese Children's Cancer Group （CCCG） hepatoblastoma （HB） risk stratification systems in terms of their prognostic prediction efficacy and chemotherapy guidance value for Chinese children with HB， aiming to identify the risk stratification system more suitable for Chinese HB patients. MethodsThis retrospective study analyzed the clinical data of 403 pediatric patients with HB aged ＜ 18 years who were initially diagnosed at The First Affiliated Hospital of Sun Yat-sen University between February 2010 and September 2023. The prognostic predictive efficacy and chemotherapy-guided value of the CHIC and CCCG risk stratification systems was compared. Statistical analysis was performed using SPSS 27.0. Results①Using the new CCCG risk stratification， the 5-year event-free survival （EFS） rates for children who received versus did not receive risk-stratified chemotherapy according to the CCCG-HB-2016 protocol were 82.5% and 67.7% （P=0.002）， respectively， and the 5-year overall survival （OS） rates were 91.5% and 85.1% （P=0.038）. Using CHIC risk stratification， the corresponding 5-year EFS rates for children who received versus did not receive risk-stratified chemotherapy according to the CCCG-HB-2016 protocol were 80.3% and 68.5% （P=0.030）， and the 5-year OS rates were 90.9% and 85.8% （P=0.151）. ②Among children treated with the CCCG-HB-2016 protocol stratified by the new CCCG system， the 5-year EFS rates for the very low-risk （6 cases）， low-risk （20 cases）， intermediate-risk （61 cases）， and high-risk （69 cases） groups were 100%， 94.1%， 94.7%， and 66.2% （P＜0.001）， respectively， and the 5-year OS rates were 100%， 100%， 96.5%， and 82.0% （P=0.017）. Among children treated with the CCCG-HB-2016 protocol stratified by the CHIC system， the 5-year EFS rates for the very low-risk （32 cases）， low-risk （22 cases）， intermediate-risk （37 cases）， and high-risk （54 cases） groups were 93.8%， 95.2%， 76.1%， and 66.8% （P=0.003）， respectively， and the 5-year OS rates were 93.1%， 100%， 89.5%， and 85.6% （P=0.190）. ③For patients receiving CCCG-HB-2016 risk-stratified chemotherapy， the P-values for EFS comparisons between the CHIC and new CCCG systems within the very low-risk， low-risk， intermediate-risk， and high-risk groups were 0.537， 0.879， 0.023， and 0.934， respectively. Among patients who received stratified chemotherapy according to the CCCG-HB-2016 regimen， the intermediate-risk group in the new CCCG risk stratification system exhibited a significant advantage in 5-year event-free survival （EFS） compared with the intermediate-risk group in the CHIC risk stratification system （94.7% vs. 76.1%）. ConclusionCompared to the CHIC risk stratification， the new CCCG stratification may offer better prognostic prediction and guidance value for chemotherapy in Chinese HB patients， with the intermediate-risk group showing superior outcomes.

Objective To explore the diagnostic value of ultrasound imaging parameters combined with ser-um progranulin(PGRN)and programmed cell death ligand 1(PD-L1)for lymph node metastasis of non-small cell lung cancer(NSCLC).Methods A total of 135 NSCLC patients admitted to Hengshui Cardiovascu-lar Hospital from February 2022 to May 2024 were selected as the NSCLC group.According to whether lymph node metastasis occurred,the NSCLC patients were divided into the metastasis group(52 cases)and the non-metastasis group(83 cases).Another 135 patients with benign lung diseases who were admitted to the hospi-tal during the same period were selected as the control group.The levels of serum PGRN and PD-L1 were de-tected by enzyme-linked immunosorbent assay.Multivariate Logistic regression analysis was conducted to ana-lyze the factors influencing lymph node metastasis of NSCLC.The receiver operating characteristic curve was used to analyze the diagnostic value of ultrasound imaging parameters[end-diastolic velocity(EDV),peak systolic velocity(PSV),and minimum axial diameter(MAD)]combined with serum levels of PGRN and PD-L1 for lymph node metastasis of NSCLC.Results Compared with the control group,the levels of serum PGRN and PD-L1 in the NSCLC group were significantly increased,and the difference was statistically signifi-cant(P<0.05).Compared with the non-metastasis group,the levels of serum PGRN and PD-L1 in the metas-tasis group were significantly increased,and the difference was statistically significant(P<0.05).Compared with the non-metastasis group,the ultrasound imaging parameters EDV,PSV and MAD in the metastasis group were significantly increased,and the difference was statistically significant(P<0.05).The results of multivariate Logistic regression analysis showed that PGRN,PD-L1,EDV,PSV,and MAD were all independ-ent risk factors affecting lymph node metastasis of NSCLC(P<0.05).The area under the curve(AUC)of serum PGRN,PD-L1 and ultrasound imaging parameters EDV,PSV and MAD for the diagnosis of lymph node metastasis of NSCLC separately was 0.805,0.792,0.745,0.738 and 0.737,respectively.The AUC of com-bined diagnosis for lymph node metastasis of NSCLC was 0.938,which was superior to that of single diagnosis(ZPGRN-combination=3.424,ZPD-L1-combination=4.076,ZEDV-combination=3.891,ZPSV-combination=4.755,ZMAD-combination=4.400,P<0.05).Conclusion Ultrasound imaging parameters combined with serum PGRN and PD-L1 have certain diagnostic value for lymph node metastasis of NSCLC.

Objective To analyze the effects of tactile vibration feedback training combined with 1 Hz repetitive tran-scranial magnetic stimulation on limb balance and walking ability of stroke patients with hemiplegia.Methods From August 2021 to August 2023,98 patients with stroke and hemiplegia who were diagnosed and treated in Daxing District People's Hospital were selected and divided into training group and stimulation group according to different treatment schemes with 49 in each.The training group was given tactile vibration feedback training,and the stimula-tion group was given tactile vibration feedback training combined with 1 Hz repetitive trans-cranial magnetic stimula-tion.The clinical symptoms,ability of keeping balance and walk,life situation and curative effect of the two groups were analyzed.Results After 8 weeks of treatment,the scores of mouth and drooling points,language impairment points,and hemiparalysis points in the two groups were all lower than those before treatment(P<0.05),and the above indexes in the stimulation group were even lower than those in the training group(P<0.05).After 8 weeks of treatment,the scores of Lindmark Balance Reaction,Berg Balance scale(BBS),stride length,10-meters maximum walking speed(10 mMWS),Barthel index(BI)and Functional Independence Measure(FIM)in both groups were higher than those before treatment(P<0.05),and the above indexes in the stimulation group were higher than those in the training group(P<0.05).After 8 weeks of treatment,the total effective rate in the stimulation group(91.84％)was higher than that in the training group(69.39％)(P<0.05).Conclusions Tactile vibration feedback training plus 1 Hz repetitive trans-cranial magnetic stimulation can significantly alleviate the clinical symptoms of stroke patients with hemiplegia and can improve their ability of keeping balance,walking and management of daily life.

Objective To address the challenges of constructing large language models for traditional Chinese medicine(TCM)classics,which are complex and expensive to fine-tune,this study explores a lightweight fine-tuning method for such models,aiming to develop a question-answering model centered on TCM classics,particularly various editions of Shang Han Lun through the ages.Methods Dataset construction involved designing prompts to guide GPT-4 in generating Q&A pairs based on Shang Han Lun and integrating them with the ShenNong_TCM_Dataset and cMedQA2 datasets.Five general-purpose large models were selected for Lora fine-tuning.The best model was chosen through evaluation,and the performance of multiple quantized versions was validated.Results After fine-tuning,the BLEU,ROUGE-1,ROUGE-2,and ROUGE-L metrics for the Qwen-7B-Chat model improved by 17.61,19.63,14.3,and 21.4,respectively,compared to the base model.Conclusion The selected model in this study is capable of effectively understanding and utilizing professional terms and concepts from TCM classics,such as Shang Han Lun,to provide accurate answers to user queries.Compared to similar models,it requires lower fine-tuning costs and computational power,contributing to the dissemination of TCM knowledge and the development of intelligent systems.

Oroxylin A (OA) is a natural flavonoid primarily derived from the plants Oroxylum indicum and Scutellaria baicalensis. Currently, OA is obtainable through chemical synthesis and exhibits polypharmacological properties, including anti-cancer, anti-inflammatory, anti-microbial, and multi-organ protective effects. The first-in-class drug OA tablets are presently undergoing phase Ib/IIa clinical trials for hepatocellular carcinoma (HCC) treatment. Substantial evidence suggests that OA demonstrates therapeutic potential against various hepatic and gastrointestinal (GI) disorders, including HCC, hepatic fibrosis, fatty liver disease, hepatitis, liver injury, colitis, and colorectal cancer (CRC). OA exerts its therapeutic effects primarily by modulating several crucial signaling pathways, including those associated with apoptosis, oxidative stress, inflammation, glucolipid metabolism, and fibrosis activation. The oral pharmacokinetics of OA is characterized by phase II metabolism, hydrolysis, and enterohepatic recycling. This review provides a comprehensive overview of the critical stages involved in the development of OA tablets, presenting a holistic perspective on the progression of this first-in-class drug from preclinical to clinical phases. It encompasses the synthesis of active pharmaceutical ingredients, pharmacokinetics, pharmacological efficacy, toxicology, drug delivery, and recent advancements in clinical trials. Importantly, this review examines the potential mechanisms by which OA may influence the gut-liver axis, hypothesizing that these interactions may confer health benefits associated with OA that transcend the limitations posed by its poor bioavailability.
Humans ; Flavonoids/pharmacokinetics* ; Tablets ; Animals ; Gastrointestinal Diseases/drug therapy* ; Liver Diseases/drug therapy* ; Drug Development ; Clinical Trials as Topic ; Scutellaria baicalensis/chemistry*

Under the context of the research-oriented hospital construction strategy and national medical talent cultivation policies,postdoctoral research stations have emerged as vital platforms for assembling high-level innovative talents.Based on the construction practices of the postdoctoral research station at Zhejiang Cancer Hospital,this paper focuses on its development trajectory from humble beginnings to being recognized as the only"Excellent medical institution-affiliated post-doctoral work station"in Zhejiang Province.It analyzes the achievements in constructing high-standard organizational management systems,high-caliber mentor teams,and high-investment talent support systems.Addressing existing challenges,the study proposes development strategies in-cluding broadening recruitment channels,exploring diversified training models,striving for inde-pendent recruitment authority,and promoting synergistic development with research-oriented hos-pital initiatives.The aim is to provide replicable experience and insights for postdoctoral platforms in tumor specialty hospitals to empower the construction of research-oriented hospitals.

Objective To systematically review and analyze the characteristics and current status of registered clinical trials on Traditional Chinese Medicine(TCM)for the prevention and treatment of overweight/obesity.Methods We conducted a comprehensive search of two primary clinical trial registration platforms,the Chinese Clinical Trial Registry and ClinicalTrials.gov,to extract registered information on TCM interventions for overweight/obesity.The search period spanned from the establishment of each registry to December 31,2024.Statistical analysis was performed on the extracted registration data.Results A total of 226 clinical studies were included,with a cumulative sample size of 25165 participants.The annual registration volume exhibited a significant upward trend.The majority of studies were interventional in design,with primary outcome measures focusing on anthropometric and metabolic indicators.Notably,only two trials fully met the international standards for clinical trial registration as outlined by the World Health Organization(WHO).Conclusion A quality assessment of the overall registration data revealed that the quality of trial registrations remains suboptimal.Issues such as inadequate standardization,transparency,and comprehensiveness were identified.Additionally,the geographical distribution of registered trials was uneven,and there is an urgent need to refine outcome measures related to TCM syndrome differentiation.

With the development of society,the incidence of obesity has increased year by year in recent years,which has seriously jeopardized public health and safety,and has been a hot spot in the field of endocrine research.At the same time,obesity is also an important cause of a variety of metabolic diseases,such as metabolic syndrome,pre-diabetes,hypertension and polycystic ovary syndrome and other diseases,but the etiology and mechanism of obesity have not been completely clear,and basic research on obesity of traditional Chinese and western medicine still needs to be widely carried out.In this paper,animal models of obesity and its complications will be comprehensively summarized,and the model principles will be elaborated in combination with TCM syndromes and western medicine mechanisms,and evaluate their merits and demerits,so as to provide references for the selection of reasonable animal models for relevant experimental studies of obesity.