ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

Objective:To systematically evaluate the risk prediction models for refeeding syndrome in critically ill patients in China and abroad, with the aim of providing feasible risk assessment tools for clinical healthcare professionals.Methods:A computerized search of PubMed, Embase, Web of Science, Cochrane Library, CINAHL, Proquest, Scopous, China Biomedical Literature Database, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP was conducted for relevant literature from database inception to July 1, 2024. Two researchers independently reviewed the literature and extracted the relevant information. Quality assessment was performed using a risk of bias assessment tool specifically designed for predictive modeling.Results:A total of 8 papers were included, reporting 8 risk prediction models for refeeding syndrome in critically ill patients, with sample sizes ranging from 109 to 806 cases, outcome event rates from 22.5% to 69.8%, and area under the curve values from 0.74 to 0.95. The most frequently reported predictors included albumin (ALB), pre-albumin (PAB), blood potassium, use of diuretics, and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores.Conclusions:The risk prediction models for refeeding syndrome in critically ill patients have good predictive performance but are still in the development stage. A high-quality, low-bias clinically applicable model should be established through multicenter, large-sample, and standardized studies.

Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 10⁷ to 1 × 10¹⁰ colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
Oxidative Stress/physiology* ; Humans ; Diabetes Mellitus/physiopathology* ; Diabetes Complications/metabolism* ; Reactive Oxygen Species/metabolism* ; Glycation End Products, Advanced/metabolism* ; Animals

Bone repair remains an important target in tissue engineering, making the development of bioactive scaffolds for effective bone defect repair a critical objective. In this study, β-tricalcium phosphate (β-TCP) scaffolds incorporated with processed pyritum decoction (PPD) were fabricated using three-dimensional (3D) printing-assisted freeze-casting. The produced composite scaffolds were evaluated for their mechanical strength, physicochemical properties, biocompatibility, in vitro pro-angiogenic activity, and in vivo efficacy in repairing rabbit femoral defects. They not only demonstrated excellent physicochemical properties, enhanced mechanical strength, and good biosafety but also significantly promoted the proliferation, migration, and aggregation of pro-angiogenic human umbilical vein endothelial cells (HUVECs). In vivo studies revealed that all scaffold groups facilitated osteogenesis at the bone defect site, with the β-TCP scaffolds loaded with PPD markedly enhancing the expression of neurogenic locus Notch homolog protein 1 (Notch1), vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and osteopontin (OPN). Overall, the scaffolds developed in this study exhibited strong angiogenic and osteogenic capabilities both in vitro and in vivo. The incorporation of PPD notably promoted the angiogenic-osteogenic coupling, thereby accelerating bone repair, which suggests that PPD is a promising material for bone repair and that the PPD/β-TCP scaffolds hold great potential as a bone graft alternative.
Calcium Phosphates/chemistry* ; Animals ; Bone Regeneration ; Rabbits ; Tissue Scaffolds ; Printing, Three-Dimensional ; Humans ; Human Umbilical Vein Endothelial Cells ; Neovascularization, Physiologic ; Osteogenesis ; Tissue Engineering/methods* ; Biomimetic Materials ; Cell Proliferation ; Angiogenesis

Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly di-agnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time.In this work,we developed a 4-mercaptophenylboronic acid gold nanoparticles(4-MPBA-AuNPs)-functionalized hydrogel microneedle(MPBA-H-MN)for bacteria detection in skin inter-stitial fluid.MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min.Surface enhanced Raman spectroscopy(SERS)detection was then performed and combined with ma-chine learning technology to distinguish and identify a variety of bacteria.Overall,the capture efficiency of this method exceeded 50％.In the concentration range of 1 × 10 7 to 1 × 10 10 colony-forming units/mL(CFU/mL),the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration.Using random forest(RF)-based machine learning,bacteria were effectively distinguished with an accuracy of 97.87％.In addition,the harmless disposal of used MNs by photothermal ablation was convenient,environmentally friendly,and inexpensive.This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

Objective To investigate the relationship between kinase insert domain receptor(KDR)rs2305948 polymorphism and clopidogrel resistance(CR)in patients with acute coronary syndrome after receiving percutaneous coronary intervention(PCI).Methods A total of 468 patients with acute coronary syndrome,who were admitted to the Zhangjiakou Municipal First Hospital of China from September 2022 to September 2023,were selected as the subjects of study.All patients received PCI treatment and took medication of clopidogrel after the treatment.The occurrence of CR was recorded.The factors influencing the occurrence of CR were analyzed.The clinical significance of KDR rs2305948 polymorphism in predicting CR in patients with acute coronary syndrome after receiving PCI was evaluated.Results Of 468 patients with acute coronary syndrome,116(24.79％)developed CR.Logistic multivariate regression analysis indicated that low-density lipoprotein cholesterol(LDL-C,95％CI=1.420-8.390,OR=3.452),type 2 vascular endothelial growth factor receptor(VEGFR-2,95％CI=1.374-8.118,OR=3.340),KDR rs2305948 T/T genotype(95％CI=1.677-9.905,OR=4.076),and T allele(95％CI=1.390-8.207,OR=3.377)were the independent factors influencing the occurrence of CR inpatients with acute coronary syndrome after receiving PCI(all P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the sensitivity,specificity,and area under ROC curve(AUC)of the T/T genotype of KDR rs2305948 in predicting CR in patients with acute coronary syndrome after receiving PCI were 75.86％,70.45％,and 0.773(95％CI=0.666-0.880)respectively.Conclusion In patients with acute coronary syndrome after receiving PCI,the risk of developing CR is higher.The KDR rs2305948 polymorphism is correlated with CR in patients with acute coronary syndrome after receiving PCI,and it has a certain predictive value for CR.

Objective To observe the therapeutic effects of Tongluo Baoshen Prescription on IgA nephropathy rats;To explore its mechanism.Methods Totally 130 SD rats were randomly divided into a normal group(20 rats)and a modeling group(110 rats).After establishing the IgA nephropathy model,the modeling group was further randomly divided into the model group,losartan potassium group and Tongluo Baoshen Prescription low-,medium-and high-dosage groups,with 20 rats in each group.Tongluo Baoshen Prescription low-,medium-and high-dosage groups were administered at dosages of 5.3,10.6 and 21.2 g/kg respectively,the losartan potassium group was given with the dosage of 5 mg/kg,the normal group and model group were given an equivalent amount of distilled water by gavage once daily.Blood,urine and kidney tissue samples were collected after 4 and 8 weeks of administration.The hemoglobin content was detected,urinary IL-1β,integrin α3β1 and serum albumin contents were detected by ELISA,and the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue were detected by RT-qPCR and Western blot,the apoptosis of renal tissue at 8 weeks of administration was detected by TUNEL staining,the expression of C3c in renal tissue was detected by immunofluorescence,the co-expression of Gprc5b,Caspase-1,NLRP3 and Nephrin were detected by immunofluorescence double labeling,the expression of Gprc5b and Nephrin in renal tissue were detected by immunohistochemistry.Results Compared with the normal group,the model group rats showed significantly increased contents of urinary IL-1β and integrin α3β1(P<0.01),with further increases in urinary integrin α3β1 over time(P<0.05);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue significantly increased(P<0.01),and the proportion of apoptosis-positive cells in renal tissue significantly increased(P<0.01),immunofluorescence results revealed that C3c exhibited granular and clumpy high-intensity deposition in the mesangial area and capillary loops of the glomeruli(P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue increased(P<0.01),while Nephrin expression significantly decreased(P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue significantly increased(P<0.01),while Nephrin significantly decreased(P<0.01).Compared with the model group,the urinary IL-1β and integrin α3β1 contents in the losartan potassium group and Tongluo Baoshen Prescription groups reduced after 4 and 8 weeks of treatment(P<0.05,P<0.01);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue decreased(P<0.05,P<0.01),and the proportion of apoptosis-positive cells in renal tissue decreased(P<0.05),the C3c deposition in renal tissue was diminished(P<0.05,P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue were decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01).Conclusion Tongluo Baoshen Prescription has a protective effect on the kidney of IgA nephropathy rats,and it can improve podocyte injury.The mechanism may be related to the inhibition of the Gprc5b/NF-κB/NLRP3 pathway.

Objective:To systematically evaluate the risk prediction models for refeeding syndrome in critically ill patients in China and abroad, with the aim of providing feasible risk assessment tools for clinical healthcare professionals.Methods:A computerized search of PubMed, Embase, Web of Science, Cochrane Library, CINAHL, Proquest, Scopous, China Biomedical Literature Database, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP was conducted for relevant literature from database inception to July 1, 2024. Two researchers independently reviewed the literature and extracted the relevant information. Quality assessment was performed using a risk of bias assessment tool specifically designed for predictive modeling.Results:A total of 8 papers were included, reporting 8 risk prediction models for refeeding syndrome in critically ill patients, with sample sizes ranging from 109 to 806 cases, outcome event rates from 22.5% to 69.8%, and area under the curve values from 0.74 to 0.95. The most frequently reported predictors included albumin (ALB), pre-albumin (PAB), blood potassium, use of diuretics, and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores.Conclusions:The risk prediction models for refeeding syndrome in critically ill patients have good predictive performance but are still in the development stage. A high-quality, low-bias clinically applicable model should be established through multicenter, large-sample, and standardized studies.

Objective To observe the therapeutic effects of Tongluo Baoshen Prescription on IgA nephropathy rats;To explore its mechanism.Methods Totally 130 SD rats were randomly divided into a normal group(20 rats)and a modeling group(110 rats).After establishing the IgA nephropathy model,the modeling group was further randomly divided into the model group,losartan potassium group and Tongluo Baoshen Prescription low-,medium-and high-dosage groups,with 20 rats in each group.Tongluo Baoshen Prescription low-,medium-and high-dosage groups were administered at dosages of 5.3,10.6 and 21.2 g/kg respectively,the losartan potassium group was given with the dosage of 5 mg/kg,the normal group and model group were given an equivalent amount of distilled water by gavage once daily.Blood,urine and kidney tissue samples were collected after 4 and 8 weeks of administration.The hemoglobin content was detected,urinary IL-1β,integrin α3β1 and serum albumin contents were detected by ELISA,and the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue were detected by RT-qPCR and Western blot,the apoptosis of renal tissue at 8 weeks of administration was detected by TUNEL staining,the expression of C3c in renal tissue was detected by immunofluorescence,the co-expression of Gprc5b,Caspase-1,NLRP3 and Nephrin were detected by immunofluorescence double labeling,the expression of Gprc5b and Nephrin in renal tissue were detected by immunohistochemistry.Results Compared with the normal group,the model group rats showed significantly increased contents of urinary IL-1β and integrin α3β1(P<0.01),with further increases in urinary integrin α3β1 over time(P<0.05);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue significantly increased(P<0.01),and the proportion of apoptosis-positive cells in renal tissue significantly increased(P<0.01),immunofluorescence results revealed that C3c exhibited granular and clumpy high-intensity deposition in the mesangial area and capillary loops of the glomeruli(P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue increased(P<0.01),while Nephrin expression significantly decreased(P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue significantly increased(P<0.01),while Nephrin significantly decreased(P<0.01).Compared with the model group,the urinary IL-1β and integrin α3β1 contents in the losartan potassium group and Tongluo Baoshen Prescription groups reduced after 4 and 8 weeks of treatment(P<0.05,P<0.01);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue decreased(P<0.05,P<0.01),and the proportion of apoptosis-positive cells in renal tissue decreased(P<0.05),the C3c deposition in renal tissue was diminished(P<0.05,P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue were decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01).Conclusion Tongluo Baoshen Prescription has a protective effect on the kidney of IgA nephropathy rats,and it can improve podocyte injury.The mechanism may be related to the inhibition of the Gprc5b/NF-κB/NLRP3 pathway.