Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.

Guided by the theory of "the kidney storing essence, governing the bones, and producing marrow", this study explored the mechanism of icariin(ICA) in regulating the osteogenic differentiation of rat bone mesenchymal stem cells(BMSCs) through caveolin-1(Cav1) via in vitro and in vivo experiments, aiming to provide a theoretical basis for the prevention and treatment of postmenopausal osteoporosis with traditional Chinese medicine(TCM). Primary cells were obtained from 4-week-old female SD rats using the whole bone marrow adherent method. Flow cytometry was used to detect the expression of surface markers CD29, CD90, CD11b, and CD45. The potential for osteogenic and adipogenic differentiation was assessed. The effect of ICA on cell viability was determined using the CCK-8 assay, and the impact of ICA on the formation of mineralized nodules was verified by alizarin red staining. A stable Cav1-silenced cell line was constructed using lentivirus. The effect of Cav1 silencing on osteogenic differentiation was observed via alizarin red staining. Western blot analysis was conducted to detect the expression of Cav1, Hippo/TAZ, and osteogenic markers such as Runt-related transcription factor 2(RUNX2) and alkaline phosphatase(ALP). The results showed that primary cells were successfully obtained using the whole bone marrow adherent method, positively expressing surface markers of rat BMSCs and possessing the potential for both osteogenic and adipogenic differentiation. The CCK-8 assay and alizarin red staining results indicated that 1×10~(-7) mol·L~(-1) was the optimal concentration of ICA for intervention in this experiment(P<0.05). During osteogenic induction, ICA inhibited Cav1 expression(P<0.05) while promoting TAZ expression(P<0.05). Alizarin red staining demonstrated that Cav1 silencing significantly promoted the osteogenic differentiation of BMSCs. After ICA intervention, TAZ expression was activated, and the expression of osteogenic markers ALP and RUNX2 was increased. In conclusion, Cav1 silencing significantly promotes the osteogenic differentiation of BMSCs, and ICA promotes this differentiation by inhibiting Cav1 and regulating the Hippo/TAZ signaling pathway.
Animals ; Mesenchymal Stem Cells/metabolism* ; Caveolin 1/genetics* ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; Cell Differentiation/drug effects* ; Female ; Signal Transduction/drug effects* ; Flavonoids/administration & dosage* ; Protein Serine-Threonine Kinases/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Cells, Cultured ; Humans

In this study, the reductive amination method was used to label IR783 on Astragalus polysaccharides(APS) for the first time, which was verified by ultraviolet-visible spectroscopy and infrared spectroscopy. Quantitative analysis methods of APS-IR783 in plasma and various tissue were established using a multifunctional microplate reader. The pharmacokinetics and tissue distribution of APS-IR783 in mice were investigated after a single intravenous injection of 30 mg·kg~(-1) APS-IR783, and pharmacokinetic parameters were calculated using DAS 2.0 software. The results showed that the APS used had a mass fraction of 93.69%, a relative molecular weight of 1.55×10~5, and a polydispersity index(PDI, M_w/M_n) of 1.73, close to a homogeneous polysaccharide. The IR783 labeling yield reached 86.50%, and the content of IR783 in APS-IR783 was 0.72%. After a single intravenous injection of 30 mg·kg~(-1), the pharmacokinetic parameters of APS in mouse plasma were as follows: T_(max) was(0.67±0.26) h; C_(max) was(1 599.29±159.30) mg·L~(-1); T_(1/2α) and T_(1/2β) were(2.29±3.06) h and(0.44±0.05) h, respectively; AUC_(0-t) was(23 398.91±2 907.03) mg·h·L~(-1); AUC_(0-∞) was(27 710.55±3 506.55) mg·h·L~(-1); MRT_(0-∞) was(34.38±12.59) h; CL was 0.001 L·h~(-1)·kg~(-1); V_z was(0.042±0.017) L·kg~(-1). The in vivo biodistribution study demonstrated that the in vivo exposure ratios of APS in different tissue were in the following order: spleen > liver > kidney > lung > heart > small intestine > muscle > large intestine > brain > stomach, where the top five tissue accounted for 87.54% of the total area under the curve(AUC). This study successfully labeled APS with a water-soluble near-infrared fluorescent probe of IR783 for the first time and revealed the pharmacokinetics and tissue distribution of APS in mice. The paper provides detailed in vivo behavior of APS after intravenous injection, which lays the foundation for the development and utilization of APS and related natural medicines.
Animals ; Mice ; Polysaccharides/chemistry* ; Tissue Distribution ; Astragalus Plant/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Fluorescent Dyes/pharmacokinetics* ; Female

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

Near infrared spectroscopy(NIRS)technology combined with chemometrics algorithms has been widely used in quantitative and qualitative analysis of food and medicine.However,traditional chemometrics methods,especially linear classification methods,often yield unsatisfactory results when addressing multi-class classification problems.Convolutional neural network(CNN)is adept at extracting deep-level features from data and suitable for handling non-linear relationships.The modeling performance of CNN depends on the size and diversity of sample,while the collection and preprocessing of NIRS sample data is often time-consuming and labor-intensive.This study proposed a NIRS qualitative analysis method based on data augmentation strategies and CNN.The data augmentation strategy included two steps.Firstly,applying Bootstrap resampling and generative adversarial network(GAN)methods to augment three NIRS datasets(Medicine,coffee and grape).Secondly,combining the original samples(Y)with the Bootstrap augmented samples(B)and GAN augmented samples(G)to obtain three augmented datasets(Y-B,Y-G and Y-B-G).Based on this,a CNN model structure suitable for these datasets was designed,consisting of 2 one-dimensional convolutional layers,1 max-pooling layer,and 1 fully connected layer.The results showed that compared to the optimal models of partial least squares discriminant analysis(PLS-DA),support vector machine(SVM),and back propagation neural network(BP),the CNN model based on Y-B dataset achieved average accuracy improvements of 3.998%,9.364%,and 4.689%for medicine(Binary classification);the CNN model based on the Y-B-G dataset achieved average accuracy improvements of 6.001%,2.004%,and 7.523%for coffee(7-class classification);and the CNN model based on the Y-B dataset achieved average accuracy improvements of 33.408%,51.994%,and 34.378%for grapes(20-class classification).It was evident that the models established based on data augmentation strategies and CNN demonstrated better classification accuracy and generalization performance with different datasets and classification categories.

Background ¹³⁷Cs in atmospheric aerosol is the product of past nuclear weapon tests and nuclear accidents. When ¹³⁷Cs is released into the atmosphere, it will deposit in dry land and marine environment, causing pollution of soil surface, water, agricultural products, and animal byproducts, and affecting public health. Objective To identify the variation pattern of ¹³⁷Cs activity concentration in aerosol and its correlation with dust concentration in Beijing area from 2017 to 2020. Methods A total of 958 aerosol samples were collected from November 1, 2017 to June 30, 2020 in Beijing with a high volume air sampler at a sampling flow rate about 600 m³·h⁻¹ and a collection time for each sample about 24 h. The activity concentration of ¹³⁷Cs in the aerosol samples was determined with a low-background high-purity germanium γ spectrometer. The dust concentration was calculated using the difference in the mass of the aerosol filter before and after sampling. The detection rate of ¹³⁷Cs and dust concentration in different seasons were compared. Spearman rank correlation test was used to analyze the correlation between ¹³⁷Cs activity concentration and dust concentration. Results From 2017 to 2020, the ¹³⁷Cs activity concentrations of 33 from 958 aerosol samples in Beijing were above the minimum detectable activityconcentration, the overall detection rate of ¹³⁷Cs was 3.4%, and the activity concentration ranged from 1.86 to 45.53 μBq·m⁻³, with a median value of 4.85 μBq·m⁻³. The detection rate of ¹³⁷Cs was highest in spring, followed by autumn, and lowest in winter and summer (8.4%, 3.0%, 1.1%, and 0.5%, respectively). The dust concentration ranged from 0.03 to 1.55 mg·m⁻³, with an average value of 0.18 mg·m⁻³. There was a statistically significant difference in the dust concentrations in spring, summer, autumn, and winter (F=45.51, P<0.05), and the highest value was 0.24 mg·m⁻³ in spring (P<0.05). The ¹³⁷Cs activity concentration was positively correlated with the dust concentration (P<0.05). Conclusion The ¹³⁷Cs activity concentration in aerosol in Beijing from 2017 to 2020 fluctuates within the range of background level, and its activity concentration is highest in spring, followed autumn, and lowest in summer and winter.

Objective:To explore the diagnosis and treatment of acquired hemophilia A (AHA ) based on the analysis of clinical data.Methods:A retrospective analysis was conducted on the clinical manifestations,laboratory characteristics,treatment,and outcomes of 25 patients diagnosed with AHA who were admitted to the Second Hospital of Hebei Medical University. Results:Among all patients,11 cases had secondary factors,including 5 cases of autoimmune diseases,3 cases of pregnancy-related disease,1 case of pemphigoid,1 case of Graves'disease,and 1 case of monoclonal gammaglobulinemia of unknown significance (MGUS ).The bleeding sites include the skin,mucous membrane,muscle,joint cavity and brain tissue.Twenty-three patients were treated with prednisone combined with cyclophosphamide (CP regimen),one patient with rituximab combined with cyclophosphamide because of femoral head necrosis,and one case with rituximab monotherapy because of gastrointestinal bleeding after prednisone treatment. Among them,23 cases achieved complete remission (CR),2 cases were partial remission (PR),and 8 cases relapsed after CR.All of 10 patients including 2 cases with PR and 8 relapsed cases after CR were treated with rituximab.At last,8 patients achieved CR,and 2 patients (both were patients with recurrence after first CR)achieved PR.These two patients achieving PR were treated with low-dose rituximab combined with bortezomib (RB regimen ).One patient reached CR after 4 cycles and the other reached CR after 6 cycles of RB regimen.After CR,4 of the 10 patients treated with rituximab received maintenance therapy with rituximab monotherapy for 1.5 to 2 years,in which,none of them relapsed.Among the 6 patients who did not receive maintenance therapy,4 patients relapsed after CR,and the median time to relapse was 15 months.Eight patients treated with CP regimen developed common infections,and two patients treated with rituximab developed severe pneumonia.All 25 patients survived until the end of follow-up.Conclusion:Skin ecchymosis,mucous hemorrhage and muscle hematoma are the most common hemorrhagic manifestations in AHA,and joint hemorrhage and cerebral hemorrhage can also occur.CP regimen is the preferred option of first-line therapy for AHA.Rituximab can be used for patients with steroid contraindication or who failed to respond to the above therapy or relapsed after effective treatment,and maintenance therapy is recommended to reduce the risk of recurrence.Meanwhile,close attention should be paid to the occurrence of infection events during rituximab treatment.Rituximab in combination with bortezomib can also be used in patients with refractory or relapsing AHA.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

OBJECTIVES: To investigate the mechanism of luteolin for inhibiting proliferation of lung cancer A549 cells. METHODS: A549 cells treated with different concentrations of luteolin for 48 h were evaluated for changes in cell viability, proliferation, reactive oxygen species (ROS) production and apoptosis using MTT assay, plate cloning assay, EdU staining, DCFH-DA assay and Hoechst33258 staining. The changes in cell autophagy were examined with MDC staining, and the expressions of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-9), autophagy-related proteins (LC3B, Beclin 1, and P62), AKT/mTOR pathway proteins, and HO-1 protein were detected using Western blotting. RESULTS: Treatment with luteolin dose-dependently inhibited the viability and proliferation of A549 cells, increased intracellular ROS levels, up-regulated the expressions of Bax, cleaved caspase-9, and Beclin 1, increased the LC3B-II/LC3B-I ratio, down-regulated the expressions of Bcl-2 and P62, and induced cell apoptosis and autophagy. Luteolin also significantly inhibited the phosphorylation of AKT and mTOR and down-regulated the expression of HO-1 protein in the cells. CONCLUSIONS Luteolin induces apoptosis and autophagy to inhibit proliferation of A549 cells by increasing ROS production, inhibiting the AKT/mTOR pathway and down-regulating HO-1 protein expression.
Humans ; TOR Serine-Threonine Kinases/metabolism* ; A549 Cells ; Reactive Oxygen Species/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Lung Neoplasms/pathology* ; Apoptosis/drug effects* ; Luteolin/pharmacology* ; Autophagy/drug effects* ; Heme Oxygenase-1/metabolism* ; Cell Survival/drug effects*

Humans ; Biopsy, Fine-Needle ; Carcinoma/pathology* ; Esophagogastric Junction/pathology* ; Cytodiagnosis ; DNA Helicases ; Nuclear Proteins ; Transcription Factors