ObjectiveThis study focused on the marketed Chinese patent medicines for the treatment of Functional Diarrhea （FDr） in China and their prescription characteristics， in order to provide support for the clinical application and research and development of anti-FDr Chinese patent medicines. MethodsCollect the information of Chinese patent medicines that have been marketed to treat FDr， use Microsoft Excel 2021 software to conduct preliminary data collation and statistical analysis， and use the ancient and modern medical record cloud platform （V2.3.9） to analyze the standardized Chinese patent medicine prescriptions from the aspects of drug nature and taste， medication characteristics and prescription rules. Results147 kinds of FDr Chinese patent medicines were included in this study. There are a total of 40 varieties of FDr Chinese patent medicines suitable for children； The distribution of dosage forms is mainly pills， tablets， and capsules. 110 prescriptions were screened， among which the proportion of Chinese patent medicines for the treatment of spleen deficiency syndrome was the highest； The top three drug use frequency were licorice， Atractylodes macrocephala， and Poria cocos； The medicinal properties are mainly warm and flat， and the medicinal taste is mostly pungent， sweet and bitter， and most of them belong to the two meridians of the spleen and stomach； The association rules analysis obtains 20 strong association pairing sets； Three drug combinations were obtained by cluster analysis. ConclusionFDr Chinese patent medicine shows unique value in clinical application， especially in the field of children. However， there are still problems such as strong professionalism in the indication expression of drug instructions， limited coverage of the medical insurance catalog， and lack of high-level evidence-based medicine and pharmacoeconomic evidence. To this end， in the future， efforts should be made to build a multi-level evidence-based evidence system， improve medication compliance， and deepen research on syndrome-based medication laws， so as to enhance the clinical application value and scientific connotation of FDr Chinese patent medicines.

BACKGROUND:Pure titanium and titanium alloy implants are widely used in the field of implant restoration due to their excellent biocompatibility and elastic modulus.However,the biological inertness of the surface of titanium-based implants leads to poor integration with surrounding bone tissues,and surface modification is required to improve the bone integration ability of titanium-based implants.OBJECTIVE:To fabricate hydroxyapatite/graphene oxide/interleukin-4 composite coatings on pure titanium substrates,and to investigate their physicochemical properties and biocompatibility of the coating materials.METHODS:Hydroxyapatite/graphene oxide/interleukin-4 composite coatings were prepared on pure titanium substrates by electrochemical deposition and freeze-drying.Titanium sheets loaded with interleukin-4 and titanium sheets loaded with hydroxyapatite/graphene oxide coatings were prepared at the same time,and the physicochemical properties of pure titanium sheets and the above three titanium sheets were characterized.MC3T3-E1 cells were inoculated on the surfaces of pure titanium sheets and the above three titanium sheets,respectively.Cell proliferation was detected by CCK-8 assay and DAPI staining.Cell activity was detected by Calcein-AM/PI staining.Cell morphology and adhesion were observed by scanning electron microscopy.RESULTS AND CONCLUSION:(1)Scanning electron microscopy,energy-dispersive X-ray spectroscopy,X-ray photoelectron spectroscopy,X-ray diffraction,and Raman spectroscopy confirmed the successful fabrication of the hydroxyapatite/graphene oxide/interleukin-4 composite coating on the titanium surface.The water contact angle of hydroxyapatite/graphene oxide/interleukin-4 group was larger than that of pure titanium group and hydroxyapatite/graphene oxide group,and smaller than that of interleukin-4 group.(2)CCK-8 assay and DAPI staining results showed that hydroxyapatite/graphene oxide/interleukin-4 coating could promote the proliferation of MC3T3-E1 cells.Calcein-AM/PI staining results showed that MC3T3-E1 cells in hydroxyapatite/graphene oxide/interleukin-4 coating group had higher activity and fewer dead cells.Scanning electron microscopy showed that MC3T3-E1 cells adhered to the surfaces of the four groups of materials with good cell morphology.Compared with the pure titanium group,the MC3T3-E1 cells in the interleukin-4 group extended more pseudopodia,the cell-cell connections were closer,and the adhesion area was larger;compared with the hydroxyapatite/graphene oxide group,the MC3T3-E1 cells in the hydroxyapatite/graphene oxide/interleukin-4 group extended more pseudopodia,the cell-cell connections were closer,and the adhesion area was larger.(3)These findings indicate that the hydroxyapatite/graphene oxide/interleukin-4 composite coating possesses favorable physicochemical and biological properties.

BACKGROUND:Pure titanium and titanium alloy implants are widely used in the field of implant restoration due to their excellent biocompatibility and elastic modulus.However,the biological inertness of the surface of titanium-based implants leads to poor integration with surrounding bone tissues,and surface modification is required to improve the bone integration ability of titanium-based implants.OBJECTIVE:To fabricate hydroxyapatite/graphene oxide/interleukin-4 composite coatings on pure titanium substrates,and to investigate their physicochemical properties and biocompatibility of the coating materials.METHODS:Hydroxyapatite/graphene oxide/interleukin-4 composite coatings were prepared on pure titanium substrates by electrochemical deposition and freeze-drying.Titanium sheets loaded with interleukin-4 and titanium sheets loaded with hydroxyapatite/graphene oxide coatings were prepared at the same time,and the physicochemical properties of pure titanium sheets and the above three titanium sheets were characterized.MC3T3-E1 cells were inoculated on the surfaces of pure titanium sheets and the above three titanium sheets,respectively.Cell proliferation was detected by CCK-8 assay and DAPI staining.Cell activity was detected by Calcein-AM/PI staining.Cell morphology and adhesion were observed by scanning electron microscopy.RESULTS AND CONCLUSION:(1)Scanning electron microscopy,energy-dispersive X-ray spectroscopy,X-ray photoelectron spectroscopy,X-ray diffraction,and Raman spectroscopy confirmed the successful fabrication of the hydroxyapatite/graphene oxide/interleukin-4 composite coating on the titanium surface.The water contact angle of hydroxyapatite/graphene oxide/interleukin-4 group was larger than that of pure titanium group and hydroxyapatite/graphene oxide group,and smaller than that of interleukin-4 group.(2)CCK-8 assay and DAPI staining results showed that hydroxyapatite/graphene oxide/interleukin-4 coating could promote the proliferation of MC3T3-E1 cells.Calcein-AM/PI staining results showed that MC3T3-E1 cells in hydroxyapatite/graphene oxide/interleukin-4 coating group had higher activity and fewer dead cells.Scanning electron microscopy showed that MC3T3-E1 cells adhered to the surfaces of the four groups of materials with good cell morphology.Compared with the pure titanium group,the MC3T3-E1 cells in the interleukin-4 group extended more pseudopodia,the cell-cell connections were closer,and the adhesion area was larger;compared with the hydroxyapatite/graphene oxide group,the MC3T3-E1 cells in the hydroxyapatite/graphene oxide/interleukin-4 group extended more pseudopodia,the cell-cell connections were closer,and the adhesion area was larger.(3)These findings indicate that the hydroxyapatite/graphene oxide/interleukin-4 composite coating possesses favorable physicochemical and biological properties.

Over the past three decades， China has made significant progress in the prevention and control of viral hepatitis， and the incidence rates of new-onset pediatric hepatitis B virus infections and acute viral hepatitis in the population have reduced to a relatively low level； however， there is still a heavy disease burden of chronic viral hepatitis in China， which severely affects the health status of the population. This study systematically summarizes the achievements of viral hepatitis prevention and control in China， analyzes existing problems and challenges， and proposes comprehensive prevention and control strategies and measures to eliminate viral hepatitis as a public health threat based on the national conditions of China， in order to provide a reference for related departments in China on how to achieve the action targets for eliminating viral hepatitis as a public health threat by 2030.

Aromatic Chinese medicinal essential oils are volatile oils extracted from aromatic Chinese herbs， which can prevent and treat respiratory infectious diseases through multiple synergistic mechanisms including pathogen inhibition， immune regulation， and inflammatory response regulation. Essential oils are primarily used externally on the body to prevent infections and alleviate symptoms through methods like inhalation， smearing， topical application， bathing， gargling or as a suppository. They can also be utilized in the environment for disinfection and air purification， through methods like diffusion， vaporization， or spraying. The external application of essential oils extracted from Chinese aromatic herbs has the advantages of convenience， quick absorption， and simultaneous influence on both the body and mind. However， there are still challenges and deficiencies in aspects such as the positioning of functions， indications， safety， and the research on the mechanism of action. It has been proposed to combine the theory of aromatic Chinese medicinals with the characteristics of essential oils， and formulate prescriptions of Chinese medicinal essential oils under the principles of traditional Chinese medicine syndrome differentiation， and prevent and treat respiratory infectious diseases efficiently， accurately， and safely， thereby expanding the clinical application of aromatic Chinese medicinals and the preventive theory of traditional Chinese medicine.

Objective: Traumatic brain injury (TBI) patients often experience massive bleeding and require blood transfusion. However, the storage duration of the transfused blood may affect the prognosis of these patients. This study explored the influence of exosomes derived from fresh and aged blood on the prognosis of rats with TBI, so as to provide theoretical support for the blood transfusion management of TBI patients. Methods: Exosomes were isolated from red blood cell (RBC) suspensions stored for 1 week and 5 weeks using ultracentrifugation method. The size, morphology and surface markers of the exosomes were identified by nanoparticle flow cytometry, transmission electron microscopy and Western blotting, respectively. A rat model of TBI was constructed using a mechanical impactor for brain injury. After the successful establishment of the model, exosomes from RBC suspensions stored for 1 week and 5 weeks were injected into the extracellular space of rat brain cells using a stereotactic syringe. Cerebral edema at day 1, 3, 7 and 14 were recorded through cranial magnetic resonance imaging (MRI) scans. Magnetic tracing technology (the tracer was Gd-DTPA solution) was used to evaluate the drug metabolism level in the extracellular space of brain cells of TBI rats. The cranial magnetic resonance imaging was scanned every 15 or 30 minutes, and the recording lasted for a total of 240 minutes. The magnetic images were imported into the 3D-Slicer software in Dicom data format for analysis. Mass spectrometry technology was used to analyze the differential proteins of exosomes from RBC suspensions stored for 1 week and 5 weeks, and functional prediction was carried out to explore the possible mechanisms by which exosomes affect the prognosis of TBI. Results: After injection of exosomes into TBI rats, the areas of cerebral edema on the day 1, 3, 7, and 14 were all significantly higher in the rats treated with exosomes from 5-week-stored RBC suspensions, with peak cerebral edema occurring at day 3. The diffusion volume of the tracer was significantly higher in TBI rats than in normal rats, which implied there was a disorder in the structure of the traumatic brain tissue in TBI rats. Compared with the rats injected with exosomes from 1-week-stored RBC suspensions, those treated with exosomes from 5-week-stored RBC suspensions showed increased tracer diffusion volume within 120 minutes. Mass spectrometry analysis identified 81 differentially expressed proteins between exosomes from RBC suspensions stored for 5 weeks vs 1 week. Among them, 93.83% (76/81) proteins had increased expression levels. The neurodegeneration-related pathways were among the most enriched pathways for upregulated proteins. Conclusion: The exosomes from aged RBC suspensions can lead to exacerbated cerebral edema, disrupted extracellular space, and suppressed metabolic rate in TBI rats, suggesting that transfusion of aged RBC suspensions may have adverse effects on TBI patients.

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Traditional Chinese medicine (TCM) serves as a treasure trove of ancient knowledge, holding a crucial position in the medical field. However, the exploration of TCM's extensive information has been hindered by challenges related to data standardization, completeness, and accuracy, primarily due to the decentralized distribution of TCM resources. To address these issues, we developed a platform for TCM knowledge discovery (TCMKD, https://cbcb.cdutcm.edu.cn/TCMKD/). Seven types of data, including syndromes, formulas, Chinese patent drugs (CPDs), Chinese medicinal materials (CMMs), ingredients, targets, and diseases, were manually proofread and consolidated within TCMKD. To strengthen the integration of TCM with modern medicine, TCMKD employs analytical methods such as TCM data mining, enrichment analysis, and network localization and separation. These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights. In addition to its analytical capabilities, a quick question and answer (Q&A) system is also embedded within TCMKD to query the database efficiently, thereby improving the interactivity of the platform. The platform also provides a TCM text annotation tool, offering a simple and efficient method for TCM text mining. Overall, TCMKD not only has the potential to become a pivotal repository for TCM, delving into the pharmacological foundations of TCM treatments, but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems, extending beyond just TCM.