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.

To evaluate the therapeutic effect of baicalein topical preparation on atopic dermatitis, we first constructed two atopic dermatitis-like mouse models induced by calcipotriol and 1-fluoro-2,4-dinitrobenzene to assess their therapeutic effect with skin tissue staining and other experiments. It was found that topical preparation of baicalein could alleviate epidermal thickening of diseased skin tissues, repair damaged skin barrier proteins, and inhibit T helper 2 cells (Th2) infiltration and mast cell infiltration and activation in lesional sites. Cyberpharmacology was utilized to analyze whether baicalein could treat atopic dermatitis by interfering with multiple pathogenesis-associated pathways. Results indicated that baicalein reduced the mRNA levels of inflammatory factors and inhibited the phosphorylation of NF-κB p65 and STAT1 proteins in keratinocyte cells. Together, the topical preparation of baicalein may be effective in alleviating atopic dermatitis-like symptoms in mice by down-regulating the phosphorylation level of NF-κB in keratinocytes, thereby decreasing the expression of inflammatory factors in keratinocytes, which provides an idea and a theoretical basis for the topical preparation of baicalein for the treatment of inflammatory skin diseases such as atopic dermatitis.

Objective: To analyze the characteristics of alcohol poisoning cases among minors receiving pre hospital 120 emergency services in Zhengzhou, providing evidence for regional management strategies of alcohol poisoning among minors. Methods: A retrospective study was conducted on 1 630 alcohol poisoning cases (aged 0-18 years) from Zhengzhou s 120 emergency system during 2017-2019 and 2023. Data on gender, age, occurrence timeframes were analyzed using t-test and χ 2 test for intergroup comparisons. Results: Annual cases were 291 (2017), 353 (2018), 483 (2019), and 503 (2023). Compared with 2017, male alcohol poisoning cases increased by 66.94% while female cases surged 104.35% by 2023. The peak incidence of alcohol poisoning among minors occurred among 16-18 year olds (85.40%), followed by 13-15 year olds (13.74%). Most cases clustered between 21:01-03:00 (60.43%), with male cases peaking at 22:01-23:00 (12.73%) and female cases peaking at 02:01-03:00 ( 11.25 %). Between 00:01-03:00, male cases progressively decreased while female cases increased. Severity distribution showed 355 mild cases (21.78%), 1 035 moderate cases (63.50%), and 240 severe cases (14.72%). Conclusions Zhengzhou region has experienced sustained growth in underage alcohol poisoning cases, predominantly occurring from evening to early morning with moderate severity, female cases demonstrate faster growth rates. Multifaceted regulatory measures should be implemented to strengthen supervision of underage drinking behaviors.

Diabetic retinopathy(DR)is a kind of microvascular disease caused by the long-term influence of diabetes mellitus(DM),and it is one of the main cause of global visual impairment and blindness.Its typical characteristics include microaneurysms,hard exudates,macular edema(DME)and neovascularization.Its pathogenesis is diverse,and the root cause is oxidative stress and advanced glycosylation end products.The nuclear red blood cell related factor 2(Nrf2)signa-ling pathway plays an important role in preventing various diseases.As one of the characteristics of DM,hyperglycemia will activate the generation of reactive oxygen species(ROS)in mitochondria.These oxidative stress factors activate the nucle-ar transcription factor κB pathway,becoming the main inducement of various complications of DM.This pathway will in-duce increased transcription of proinflammatory cytokines,including tumor necrosis factor-alpha,transforming growth fac-tor-beta and interleukin-1.The active ingredients of traditional Chinese medicine have significant antioxidant,anti-inflam-matory,anti-apoptotic and angiogenesis-promoting effects,and can block the progression of DR through various mecha-nisms.In this article,the research status of traditional Chinese medicine targeting the Nrf2 signaling pathway in the preven-tion and treatment of DR is reviewed to guide clinical and scientific research.

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*

This study investigated the effects and underlying mechanisms of the luteolin-naringenin combination(LN)on liver injury induced by acetaminophen(APAP).Forty-eight Kunming mice were randomly allocated into six groups:a normal control group,an APAP-induced liver injury model group,a positive drug treatment group,and three LN treatment groups with low,medium,and high doses.After the final drug administration,the mice were fasted for 12 hours prior to eu-thanasia for sample collection.Serum transaminase activity,oxidative stress indices,and hematoxy-lin-eosin(HE)staining were assessed to evaluate the effects of LN on APAP-induced hepatic inju-ry.Additionally,Western blot analysis was conducted to examine the expression levels of sphingo-sine kinase 1(SPHK1)and endoplasmic reticulum stress(ERS)-related proteins,thereby elucida-ting the potential mechanisms by which LN mitigates APAP-induced liver injury.The results dem-onstrated that varying concentrations of LN effectively ameliorated serum aminotransferase activi-ty and oxidative stress levels induced by APAP in a dose-dependent manner.Histopathological ex-amination via HE staining revealed significant improvement in APAP-induced liver tissue injury following treatment with different concentrations of LN.Furthermore,Western blot analysis indi-cated that the protein expressions of SPHK1,CHOP,p-IRE1α,ATF6,p-PERK,p-eIF2α,and ATF4 were markedly reduced after administration of various concentrations of LN.The results demonstrate that LN exhibits a significant protective effect against APAP-induced liver injury by inhibiting the SPHK1-mediated aberrant expression of ERS-related molecules.This study high-lights the importance of targeting SPHK1 in the treatment of APAP liver injury and provides a no-vel therapeutic approach through the multi-target and multi-pathway combination of monomers.

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.

Objective To investigate the changes of residual radioactivity at different time points after 131I treatment in the patients with differentiated thyroid cancer(DTC)and influencing factors.Methods A to-tal of 235 patients with DTC receiving 131I treatment in this hospital from January 2021 to June 2023 were se-lected as the study subjects and divided into the high dose group(＞5.55 GBp,n=56)and low dose group(≤5.55 GBp,n=179)according to the treatment dose.The clinical data of the two groups were collected and the changes of residual radioactivity after 131I treatment were compared between the two groups.The binary re-gression was used to analyze its influencing factors.Results The sex,age,BMI,basic metabolic rate(BMR)and serum thyroglobulin antibody(TgAb)had no statistical differences between the two groups(P＞0.05).The proportions of serum thyroglobulin(TG)＜1 ng/mL,131I first time treatment and residual thyroid ratio prompted by the whole body 131I scan after treatment in the low dose group were significantly higher than those in the high dose group(P＜0.05).The residual radioactivity in the two groups was significantly de-creased with time extension.The residual radioactivity at 24,48,72 h after treatment in the low dose group was significantly lower than that in the high dose group(P＜0.05).The binary logistic regression analysis re-sults showed that the T stage and treatment dose were the influencing factors of residual radioactivity after 131I treatment.Conclusion The residual radioactivity after 131I treatment in the patients with DTC shows the significant decreasing trend with time extension,this change trend has an active significance for further opti-mizing and perfecting the isolation and protection scheme.For the patients with high T stage and big treat-ment dose,the isolation time should exceed 72 h.