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.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

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*

ObjectiveTo investigate the feasibility and safety of endoscopic retrograde cholangiopancreatography （ERCP） combined with oral cholangiopancreatography in the treatment of major duodenal papilla gallbladder polyps. MethodsA retrospective analysis was performed for the clinical data of eight patients with choledocholithiasis and gallbladder polyps who underwent ERCP and combined with oral cholangiopancreatography for major duodenal papilla cholecystectomy in Center of Digestive Endoscopy， Jilin People’s Hospital， from May 2022 to June 2024， and related data were collected， including the success rate of surgery， the technical success rate of gallbladder polyp removal， the superselective method of cystic duct， the time of operation， the time of gallbladder polyp removal， and surgical complications. ResultsBoth the success rate of surgery and the technical success rate of gallbladder polyp removal reached 100%， and of all eight patients， three patients used guide wire to enter the gallbladder under direct view， while five patients received oral cholangiopancreatography to directly enter the gallbladder. The time of operation was 51.88±12.34 minutes， and the time of gallbladder polyp removal was 23.13±10.94 minutes. The diameter of gallbladder polyp was 2‍ ‍—‍ ‍8 mm， and pathological examination showed inflammatory polyps in three patients， adenomatous polyps in one patient， and cholesterol polyps in four patients. There were no complications during or after surgery. The patients were followed up for 2‍ ‍—‍ ‍27 months after surgery， and no recurrence of gallbladder polyp was observed. ConclusionOral cholangiopancreatography is technically safe and feasible in endoscopic major duodenal papilla cholecystectomy.

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.

Objective This study aims to explore the effects of Minimally Invasive Extracorporeal Circulation(MECC)on systemic inflammatory response and transfusion requirements following Coronary Artery Bypass Grafting(CABG).Methods A total of 126 patients who underwent CABG from January 2023 to January 2024 were selected and randomly divided into an observation group and a control group,with 63 patients in each group.The observation group received MECC,while the control group was treated with Conventional Extracorporeal Circulation(CECC).Inflammatory response indicators,immune system function,coagulation function,renal function,cardiac function,and clinical symptoms were monitored preoperatively and at 24,48,and 72 hours postoperatively for comparison and analysis.Results At 24 hours postoperatively,CRP,IL-6 and TNF-α levels in the observation group were(18.5±3.7)mg/L,(15.2±3.4)pg/mL and(25.3±5.6)pg/mL,respectively,which were significantly lower than those in the control group(P＜0.05).At 48 hours postoperatively,the CD4+/CD8+ratio in the observation group was 1.6±0.3,which was higher than that in the control group(P＜0.05).At 72 hours postoperatively,the PT and APTT in the observation group were(12.1±1.2)seconds and(30.4±3.2)seconds,respectively,which were significantly lower than those in the control group(P＜0.05).Additionally,72 hours after surgery,SCr and BUN in the observation group were(1.1±0.2)mg/dL and 14.6±3.1 mg/dL,respectively,which were significantly lower than those in the control group(P＜0.05).In terms of cardiac function indexes,at 24 hours postoperatively,CI,LVEF,cTnⅠ and BNP in the observation group were(2.6±0.5)L/min/m2,(55.6±4.0)％,(0.14±0.03)ng/mL,and(280±30)pg/mL,respectively,which were significantly better than those in the control group(P＜0.05).At all postoperative time points,the VAS score,complication rate,length of hospital stay and ICU stay were significantly better in the observation group than in the control group(P＜0.05),with the VAS score at 24 hours postoperatively being(4.8±1.2)compared to(5.5±1.3)in the control group(P＜0.05).Conclusions MECC demonstrates significant advantages in attenuating systemic inflammatory response after CABG,protecting multi-system function,reducing postoperative blood transfusion requirements,and improving postoperative recovery.Compared with traditional extracorporeal circulation,MECC effectively reduce postoperative inflammatory reactions and complications,enhancing the quality of life for patients post-surgery,and shows broad clinical application prospects.

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.

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.

Objective:To evaluate the safety and efficacy of enhanced recovery after surgery(ERAS) in the perioperative period of congenital choledochal cysts in children.Methods:This is a multicenter prospective randomized controlled study. The clinical data of 273 pediatric congenital choledochal cysts(CCC) patients who underwent surgery at 14 medical centers with complete follow-up data were collected through the medical data analysis platform. Among them, 123 cases in ERAS group were managed perioperatively in strict accordance with ERAS mode, and 150 cases in conventional group were managed according to traditional mode. The length of hospital stay,time to first farting, time to complete feeding, the incidence of complications, cost and readmission rate within 30 days,stress indexes and liver function were compared between the two groups.Results:Compared with the conventional group, median time to start farting (2.0 d vs. 3.0 d, P<0.001), median time to complete feeding (5.0 d vs. 7.0 d, P<0.001), median postoperative hospitalization time (6.0 d vs. 9.0 d, P<0.001),the median total length of stay(13.0 d vs. 15.0 d, P<0.001) were shorter,the median hospitalization cost (37,000 yuan vs.43,000 yuan P<0.001) was lower, and stress indexes recovered quickly. The incidence of postoperative hospital stay and readimission rate within 30 d were not statistically different between the two groups. Conclusion:It is safe and feasible to implement ERAS for children with CCC in the perioperative period, which can reduce stress response, speed up recovery,and save medical costs.