Objective: To prepare the erythrocyte-liposome drug delivery system to enhance the therapeutic effect of drugs on tumors and inhibit tumor metastasis. Methods: This study prepared and characterized paclitaxel (PTX)-plerixafor (AMD3100) liposomes (Lips), developed the erythrocyte-liposome drug delivery system, and evaluated its targeting efficiency and therapeutic efficacy through a series of in vitro cellular and in vivo animal experiments. Results: The particle size of PTX-AMD-Lips was (186.4±0.83) nm. Drug encapsulation efficiency of PTX-AMD-Lips was (75.50±5.27)% for PTX and (88.31±2.45)% for AMD. The Binding efficiency between RBC and liposomes in the drug delivery system was (69.93±2.55)%. Vitro cellular experiments revealed that PTX-AMD-Lips significantly inhibited tumor cell migration. In vivo animal experiments, the erythrocyte-liposome drug delivery system significantly increased drug accumulation in the lungs. At the experimental endpoint, the quantitative fluorescence signal of tumor size measured (4.04±0.44)×10 for the PTX-Lips group, and (5.14±3.40)×10 for the RBC-PTX-AMD-Lips group. Conclusion: The erythrocyte-liposome drug delivery system could enhance the lung-specific targeting capability of liposomes, kill tumor cells and suppress further metastasis effectively.

Objective: To verify the inhibitory effect of a carbon monoxide hemoglobin-based oxygen carrier (CO-HBOC) on the fibrotic process in mice with idiopathic pulmonary fibrosis (IPF), clarify its efficacy difference compared with hemoglobin-based oxygen carriers (HBOCs), and elucidate its mechanism of action via proteomic analysis. Methods: CO-HBOC was prepared using gas loading technology. An IPF mouse model was established and the mice were randomly divided into a normal saline control group, an HBOC treatment group, and a CO-HBOC treatment group. The fibrotic area percentage was analyzed using Micro-CT; the degree of inflammatory infiltration and fibrosis in lung tissue was assessed by pathological section staining (e.g., HE and Masson staining); and differentially expressed proteins in lung tissue of IPF mice after CO-HBOC treatment were screened using proteomic technology. Results: Micro-CT results showed that the mean fibrotic area percentage in the CO-HBOC treatment group on day 21 was (8.89±0.98)%, which was better than that of the HBOC group (16.5±1.732)% and the normal saline group (30.75±6.45)% (P<0.05). HE and Masson staining results showed that the CO-HBOC group had reduced inflammatory cell infiltration and significantly decreased collagen fiber deposition in lung tissue, with a mean pathological score of 3.33±0.58, which was lower than that of the normal saline control group (8.33±1.53)(P<0.05); the mean collagen-positive area percentage was (3.33±1.53)%, significantly lower than that of the normal saline control group (14.00±3.61)% (P<0.05). Proteomic analysis identified 330 differentially expressed proteins, which were mainly enriched in inflammatory response regulatory pathways (such as the complement and coagulation cascades), and the expression changes of complement proteins may be the core target of CO-HBOC's anti-fibrotic effects. Conclusion: CO-HBOC can inhibit inflammatory responses and regulate fibrosis-related signaling pathways, there-by effectively inhibiting the fibrotic process in IPF mice, with superior efficacy to HBOC. Its mechanism of action involves the regulation of complement cascade-related signaling pathways and complement protein expression, providing an experimental and theoretical basis for targeted therapy of IPF.

Objective: To enhance the ability of nanoparticles to target and bind tumor cells by constructing a neutrophil hitchhiking system based on hyaluronic acid (HA)-modified dual-drug loaded lipid nanoparticles. Methods: Lipid nanoparticles (LNPs) were prepared using microfluidic technology, and the nitrogen/phosphate (N/P) ratio, flow rate ratio, and drug-to-lipid ratio were optimized. HA-modified LNPs (HA-LNPs) were prepared and characterized. The interaction between the nanoparticles and tumor cells was evaluated through in vitro cell experiments. Results: The optimal preparation conditions for LNPs are N/P=8, flow rate ratio=5, and drug-to-lipid ratio=1∶30 (w∶w). HA-LNPs has a particle size of (177.28±2.41) nm, a polydispersity index (PDI) of 0.198±0.10, and an siRNA encapsulation efficiency of (91.37±0.47)%. The optimal binding rate with neutrophils was (98.64±2.34)%. Conclusion: An HA-modified dual-drug loaded lipid nanoparticle-neutrophil hitchhiking system was successfully constructed, enhancing the synergistic anti-tumor activity of the nanomedicine and the uptake of nanoparticles by tumor cells, providing a novel delivery strategy for targeted therapy of bone marrow tumors.

ObjectiveTo compare the contents and relative molecular weight distributions of proteins and polypeptides in Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules of Hirudo single medicinal preparations， to evaluate the in vitro anticoagulant， antiplatelet and fibrinolytic activities of the three preparations， and to investigate the effects of temperature， pH and digestive enzymes on the anticoagulant activities of the three preparations. MethodsThe contents of soluble proteins and polypeptides in the three preparations were determined by bicinchoninic acid assay（BCA） and Bradford method， and the relative molecular weight distributions of the three preparations were determined by electrophoresis combined with gel chromatography. The antithrombin activity of the three preparations was evaluated by fibrinogen-thrombin time（Fibg-TT） method， and their anticoagulant activities were further assessed by the elongations of activated partial thromboplastin time（APTT）， prothrombin time（PT） and thrombin time（TT）. The antiplatelet aggregation activities of the three preparations were measured by turbidimetry and the fibrinolytic activities were measured by fibrin plate method. Relative TT was used as index to investigate the effects of temperature， pH and digestive enzyme buffer on anticoagulant activities of the three preparations. ResultsAt the lowest single dosage， the contents of proteins and polypeptides were in the order of Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. Both Huoxue Tongmai capsules and Maixuekang capsules had 11 electrophoretic bands between 4.0 kDa and 90 kDa， the bands of Maixuekang capsules were more clear in the range of >25 kDa， and there was 1 obvious band at 14 kDa for the two capsules. Huoxue Tongmai capsules had one specific band at 9.0 kDa and Maixuekang capsules had one specific band at 48.0 kDa. Naoxuekang dropping pills only had 2 electrophoretic bands at 6.5 kDa and 8.5 kDa， primarily containing peptides below 2 kDa， most of which were oligopeptides. The anticoagulant activity concentrations of the three preparations exhibited a certain dose-dependent effect. At the lowest single dosage， The anticoagulant activity concentrations were ranked as Naoxuekang dropping pills>Huoxue Tongmai capsules>Maixuekang capsules. The prolongation effect of the three preparations on coagulation time was dose-dependent. At the same concentration， the prolongation effect of Naoxuekang dropping pills and Huoxue Tongmai capsules was APTT prolongation rate>TT prolongation rate>PT prolongation rate， whereas for Maixuekang capsules， the sequence was TT prolongation rate>APTT prolongation rate>PT lengthening rate. At the single minimum dosage， the order of APTT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules≈Naoxuekang dropping pills， the order of PT prolongation rate was Naoxuekang dropping pills≈Maixuekang capsules>Huoxue Tongmai capsules， and the order of TT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. The three preparations showed dose-dependent effects on platelet aggregation induced by adenosine diphosphate（ADP） and arachidonic acid（AA）， and the effect induced by ADP was stronger than that induced by AA. The anti-platelet aggregation effect of Naoxuekang dropping pills was significantly stronger than that of Maixuekang capsules（P<0.01）， whereas Huoxue Tongmai capsules had the effect of promoting platelet aggregation. None of the three preparations had the ability to dissolve fibrin. The anticoagulant activity of Naoxuekang dropping pills was least affected by heating， while the activities of the two capsules decreased significantly within 5 min above 80 ℃， and continued to decrease within 2 h. Compared with pure water， the anticoagulant activities of the three preparations could be increased by 1-3 times under strong acidity（pH 1-3）. In the pepsin buffer， the anticoagulant activity of Naoxuekang dropping pills could be increased by 1-3 times， while the anticoagulant activities of Huoxue Tongmai capsules and Maxuekang capsules were significantly decreased， the lowest levels were about 60% and 20%， respectively. In trypsin buffer， the anticoagulant activities of Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules decreased significantly， and the lowest levels decreased to about 41%， 41% and 35%， respectively. ConclusionThe contents of proteins and polypeptides and relative molecular weights of the preparations derived from lyophilized fresh Hirudo powder， dried Hirudo powder and reflux extract of Hirudo decrease sequentially， and the anticoagulant activity decrease gradually， but the anticoagulant pathway is different. And the anti-platelet aggregation activity of the reflux extract is significantly enhanced. The heat resistance and gastrointestinal stability of the three preparations increase successively， and the first two are suitable for enteric-soluble preparations， while the latter is suitable for routine oral administration. The above results can provide data reference for the rationality of different preparation methods， active substances， pharmacodynamics and mechanism of Hirudo preparations.

Objective To investigate the feasibility of magnetic tracer technique for locating pulmonary nodules.Methods A tracer magnet and a matching puncture instrument were designed by ourselves for locating pulmonary nodules.After preliminarily verifying the feasibility of the operation in the isolated lung,four beagle dogs were used as animal models to perform puncture localization of the assumed lesions in the upper lobe of the right lung under the guidance of X-ray by using self-designed tracer magnets and puncture instruments,and the positioning effect was observed and evaluated after thorax opening.The operation time required for the tracer magnet implantation,whether there is bleeding at the puncture site,whether the tracer magnet is displaced,and the positioning time of pulmonary nodules after thorax opening were recorded.Results Two tracer magnets were successfully inserted into the upper lobe of the right lung under X-ray guidance in four beagle dogs,and the magnets were successfully attracted and fixed.The median insertion time of the tracer magnet was 5 minutes(4 to 7 minutes),and the insertion process was smooth without bleeding at the puncture site.After thorax opening,oval forceps were used to conveniently locate the location of the tracer magnet,achieving accurate positioning of pulmonary nodules with a median positioning time of 13 seconds(10 to 17 seconds),and the tracer magnet did not shift during the whole process.Conclusion The magnetic tracer technique is simple to operate and pricise for localization of pulmonary nodules.With further optimization of the operation process,this technique is expected to be applied in clinic.

Objective To investigate the feasibility of magnetic tracer technique for locating pulmonary nodules.Methods A tracer magnet and a matching puncture instrument were designed by ourselves for locating pulmonary nodules.After preliminarily verifying the feasibility of the operation in the isolated lung,four beagle dogs were used as animal models to perform puncture localization of the assumed lesions in the upper lobe of the right lung under the guidance of X-ray by using self-designed tracer magnets and puncture instruments,and the positioning effect was observed and evaluated after thorax opening.The operation time required for the tracer magnet implantation,whether there is bleeding at the puncture site,whether the tracer magnet is displaced,and the positioning time of pulmonary nodules after thorax opening were recorded.Results Two tracer magnets were successfully inserted into the upper lobe of the right lung under X-ray guidance in four beagle dogs,and the magnets were successfully attracted and fixed.The median insertion time of the tracer magnet was 5 minutes(4 to 7 minutes),and the insertion process was smooth without bleeding at the puncture site.After thorax opening,oval forceps were used to conveniently locate the location of the tracer magnet,achieving accurate positioning of pulmonary nodules with a median positioning time of 13 seconds(10 to 17 seconds),and the tracer magnet did not shift during the whole process.Conclusion The magnetic tracer technique is simple to operate and pricise for localization of pulmonary nodules.With further optimization of the operation process,this technique is expected to be applied in clinic.

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*

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

Osteoporotic fractures(OPF) refer to the fractures caused by minor violence in the state of osteoporosis, seriously threatening the life and health of elderly patients. Drug and surgical therapies have limitations such as single targets, diverse adverse reactions, and poor prognosis. Kidney-tonifying traditional Chinese medicine(TCM) has good potential in the treatment of OPF. TCM can promote the healing of OPF by promoting angiogenesis in the early stage of bone healing, promoting osteogenic differentiation of bone marrow mesenchymal stem cells in the stage of bone repair, maintaining the balance of osteogenic and osteoclastic system in the stage of bone remodeling, and regulating the oxidative stress responses throughout the process of OPF healing. TCM can alleviate the pathological state of osteoporosis and promote fracture healing in OPF patients via multiple pathways and targets, demonstrating the advantages and potential of biphasic regulation.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Osteoporotic Fractures/metabolism* ; Animals ; Fracture Healing/drug effects* ; Medicine, Chinese Traditional ; Kidney/metabolism* ; Osteogenesis/drug effects*

[Objective] To investigate the effect of Shenmai injection on the preservation quality of suspended red blood cells of high hemoglobin population in Xizang plateau. [Methods] Whole blood (400 mL, n=8) collected by the Xizang Autonomous Region Blood Center was centrifuged at 3 000 g for 10 minutes to remove most of the plasma, followed by the addition of 100 mL of MAP preservation solution to obtain plateau suspended red blood cells, which were then divided into three equal portions. One portion was the control group, and another part had 15 mL of MAP preservation solution added, which was the dosage group. The third portion involved diluting Shenmai injection with MAP, followed by addition of 15 mL of MAP preservation solution containing Shenmai to the red blood cells, resulting in a final concentration of Shenmai injection of 1%, which was the Shenmai group. Blood routine, pH value, electrolytes, glucose, lactate, free Hb, adenosine triphosphate (ATP), P50, phosphatidylserine (PS) and other indicators were detected at day 1, 21 and 35, respectively. [Results] The Hb concentration and Hct of the dosage group and the Shenmai group were significantly lower than those of the control group, with values of (179.3±17.8) vs (181.0±17.1) vs (199.1±19.5) g/L for Hb concentration and (53.2±2.6)% vs (53.3±2.5)% vs (58.4±3.1)% for Hct. The three groups maintained this pattern until the end of storage. In the middle and late stages of preservation, the glucose and Na⁺ contents in the dosage group and the Shenmai group were higher than those in the control group, while the lactate and K⁺ contents were lower than those in the control group. At the end of storage, the glucose and Na⁺ content of the Shenmai group was higher than that of the dosage group, while the lactate and K⁺ content were lower than that of the dosage group. From day 1 to day 35 of storage, the hemolysis rate of the Shenmai group was significantly lower than that of the control group and the dosage group. On day 21 and 35 of storage, the PS expression rate in the Shenmai group was significantly lower than that in the control group and the dosage group, which were (6.52±0.40)% vs (7.24±0.91)% vs (8.27±0.93)% and (7.29±0.53)% vs (9.37±0.82)% vs (8.39±0.76)%, respectively. [Conclusion] The hemolysis rate and PS of suspended red blood cells of Xizang high altitude prepared by adding Shenmai injection were significantly lower than those in the control group and the dosage group, which was conducive to reducing hemolysis and slowing down the aging of red blood cells, and had a certain improvement on the preservation quality of suspended red blood cells in Xizang plateau people.