OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Risks of food safety induced by small molecule drug residues in animal food and environment have become an increasing public concern,so it is necessary to develop highly sensitive and easy-to-operate techniques to detect small molecules.Herein,a metasurface plasma resonance(MetaSPR)sensor chip coupled with gold nanoparticles(AuNPs)was developed for detection of enrofloxacin(ENR)based on competitive immunoassay.The detection range of the sensor for ENR was 0.025-3.2 ng/mL,and the detection limit(3σ)was 20 pg/mL.The biosensor showed excellent performance including high selectivity,good stability,ease to operate and high throughput,etc.The developed method was applied to detection of ENR residues in real samples,with recoveies of 96.0% -105.0%.The proposed sensing strategy provided new technique reference for detection of other small molecules in the field of residue analysis in food safety and environment monitoring.

Objective:To establish venetoclax-resistant acute myeloid leukemia(AML)cell lines,assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family,and investigate their resistance mechanisms.Methods:CCK-8 method was used to screen AML cell lines(MV4-11,MOLM13,OCI-AML2)that were relatively sensitive to venetoclax.Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines.Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry.BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients.Results:Venetoclax-resistant cell lines of MV4-11,MOLM13,and OCI-AML2 were successfully established,with IC50 values exceeding 10-fold.Under the same concentration of venetoclax,the apoptosis rate of resistant cells decreased significantly(P＜0.05).BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins(such as BIM,BID and NOXA).RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines.Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results.Conclusion:The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax.The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM,BID,and NOXA,which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.

Objective:To explore the application strategies and clinical effects of superior gluteal artery perforator tissue flaps in repairing stage Ⅳ pressure ulcers in the sacrococcygeal region.Methods:This study was a retrospective observational study. From July 2019 to April 2024, 89 patients with stage Ⅳ pressure ulcers in the sacrococcygeal region who met the inclusion criteria were admitted to the First Affiliated Hospital of Nanchang University, including 59 males and 30 females, aged 21 to 84 years. There were 89 sacrococcygeal pressure ulcers, with an area of 5.0 cm×4.0 cm-21.0 cm×21.0 cm after debridement. According to the shape, size, and depth of the wounds after debridement, combined with the elasticity and texture of the skin around the wounds, and the principle of minimizing damage to the donor area, the appropriate forms of superior gluteal artery perforator tissue flaps were cut for wound repair in the following three conditions. (1) For wounds with a round shape, an area of 5.0 cm×5.0 cm-21.0 cm×21.0 cm, and a depth of 1.0-3.5 cm, the superior gluteal artery perforator propeller flap or myocutaneous flap, bilobed superior gluteal artery perforator relay flap, and bilateral superior gluteal artery perforator rotational flap were used. (2) For wounds with an oval shape, an area of 5.0 cm×4.0 cm-18.5 cm×10.5 cm, and a depth of 1.0-3.0 cm, the superior gluteal artery perforator propeller flap or myocutaneous flap, unilateral superior gluteal artery perforator propeller flap combined with contralateral superior gluteal artery perforator V-Y advanced flap or keystone flap were used. (3) For wounds with a fusiformis shape, an area of 7.0 cm×4.0 cm-17.5 cm×6.0 cm, and a depth of 1.5-5.0 cm, the unilateral or bilateral superior gluteal artery perforator V-Y advanced flap, superior gluteal artery perforator keystone flap, or superior gluteal artery perforator keystone flap combined with gluteus maximus muscle flap were used. In this group of patients, a total of 40 superior gluteal artery perforator propeller flaps (with an resection area of 11.0 cm×6.0 cm-17.0 cm×11.0 cm), 22 superior gluteal artery perforator propeller myocutaneous flaps (with an resection area of 10.0 cm×5.0 cm-14.0 cm×8.0 cm), 7 bilobed superior gluteal artery perforator relay flaps (with a main flap resection area of 5.5 cm×5.5 cm-18.0 cm×11.5 cm and a side flap resection area of 4.5 cm×3.0 cm-11.0 cm×6.5 cm), 5 bilateral superior gluteal artery perforator rotational flaps (with a total resection area of 20.0 cm×16.0 cm-26.0 cm×21.0 cm on both sides), 14 superior gluteal artery perforator V-Y advanced flaps (with an resection area of 12.0 cm×10.0 cm-18.0 cm×18.0 cm), 13 superior gluteal artery perforator keystone flaps (with an resection area of 13.0 cm×6.5 cm-19.0 cm×18.0 cm), and 3 gluteus maximus muscle flaps (with an resection area of 8.0 cm×3.0 cm-15.0 cm×4.5 cm). The donor area wounds were all directly sutured. The survival of tissue flaps was observed and the incidence rate of delayed wound healing in the reception area was calculated, and wound healing in the donor area was observed. The appearance and texture of tissue flaps and recurrence of pressure ulcers were followed up.Results:After surgery, all bilateral superior gluteal artery perforator rotational flaps, superior gluteal artery perforator V-Y advanced flaps, superior gluteal artery perforator keystone flaps, and gluteus maximus muscle flaps survived well. There were 6 cases of delayed wound healing in the reception area after surgery, with an incidence rate of 6.7% (6/89). Two patients had incision dehiscence in the donor area wounds due to postoperative bleeding, the wounds healed after debridement, vacuum sealing drainage, and dressing change. The wounds in the donor area of the remaining patients healed well. Six patients were lost to follow-up. Eighty-three patients were followed up for 3-48 months, of whom 4 patients died. Among the remaining 79 patients, 3 cases had pressure ulcers recur due to improper nursing, while the rest of the patients had tissue flaps with good appearance and soft texture and no recurrence of pressure ulcers.Conclusions:Based on the characteristics of wound shape, size, and depth after debridement of stage Ⅳ pressure ulcers in the sacrococcygeal region, individualized selection of flap, myocutaneous flap, or a combination of flap and gluteus maximus muscle flap based on the perforating branch of the superior gluteal artery perforator can achieve good clinical repair results. The postoperative tissue flap survived well, with a good appearance, soft texture, and less recurrence of pressure ulcers.

Objective:To explore the application strategies and clinical effects of superior gluteal artery perforator tissue flaps in repairing stage Ⅳ pressure ulcers in the sacrococcygeal region.Methods:This study was a retrospective observational study. From July 2019 to April 2024, 89 patients with stage Ⅳ pressure ulcers in the sacrococcygeal region who met the inclusion criteria were admitted to the First Affiliated Hospital of Nanchang University, including 59 males and 30 females, aged 21 to 84 years. There were 89 sacrococcygeal pressure ulcers, with an area of 5.0 cm×4.0 cm-21.0 cm×21.0 cm after debridement. According to the shape, size, and depth of the wounds after debridement, combined with the elasticity and texture of the skin around the wounds, and the principle of minimizing damage to the donor area, the appropriate forms of superior gluteal artery perforator tissue flaps were cut for wound repair in the following three conditions. (1) For wounds with a round shape, an area of 5.0 cm×5.0 cm-21.0 cm×21.0 cm, and a depth of 1.0-3.5 cm, the superior gluteal artery perforator propeller flap or myocutaneous flap, bilobed superior gluteal artery perforator relay flap, and bilateral superior gluteal artery perforator rotational flap were used. (2) For wounds with an oval shape, an area of 5.0 cm×4.0 cm-18.5 cm×10.5 cm, and a depth of 1.0-3.0 cm, the superior gluteal artery perforator propeller flap or myocutaneous flap, unilateral superior gluteal artery perforator propeller flap combined with contralateral superior gluteal artery perforator V-Y advanced flap or keystone flap were used. (3) For wounds with a fusiformis shape, an area of 7.0 cm×4.0 cm-17.5 cm×6.0 cm, and a depth of 1.5-5.0 cm, the unilateral or bilateral superior gluteal artery perforator V-Y advanced flap, superior gluteal artery perforator keystone flap, or superior gluteal artery perforator keystone flap combined with gluteus maximus muscle flap were used. In this group of patients, a total of 40 superior gluteal artery perforator propeller flaps (with an resection area of 11.0 cm×6.0 cm-17.0 cm×11.0 cm), 22 superior gluteal artery perforator propeller myocutaneous flaps (with an resection area of 10.0 cm×5.0 cm-14.0 cm×8.0 cm), 7 bilobed superior gluteal artery perforator relay flaps (with a main flap resection area of 5.5 cm×5.5 cm-18.0 cm×11.5 cm and a side flap resection area of 4.5 cm×3.0 cm-11.0 cm×6.5 cm), 5 bilateral superior gluteal artery perforator rotational flaps (with a total resection area of 20.0 cm×16.0 cm-26.0 cm×21.0 cm on both sides), 14 superior gluteal artery perforator V-Y advanced flaps (with an resection area of 12.0 cm×10.0 cm-18.0 cm×18.0 cm), 13 superior gluteal artery perforator keystone flaps (with an resection area of 13.0 cm×6.5 cm-19.0 cm×18.0 cm), and 3 gluteus maximus muscle flaps (with an resection area of 8.0 cm×3.0 cm-15.0 cm×4.5 cm). The donor area wounds were all directly sutured. The survival of tissue flaps was observed and the incidence rate of delayed wound healing in the reception area was calculated, and wound healing in the donor area was observed. The appearance and texture of tissue flaps and recurrence of pressure ulcers were followed up.Results:After surgery, all bilateral superior gluteal artery perforator rotational flaps, superior gluteal artery perforator V-Y advanced flaps, superior gluteal artery perforator keystone flaps, and gluteus maximus muscle flaps survived well. There were 6 cases of delayed wound healing in the reception area after surgery, with an incidence rate of 6.7% (6/89). Two patients had incision dehiscence in the donor area wounds due to postoperative bleeding, the wounds healed after debridement, vacuum sealing drainage, and dressing change. The wounds in the donor area of the remaining patients healed well. Six patients were lost to follow-up. Eighty-three patients were followed up for 3-48 months, of whom 4 patients died. Among the remaining 79 patients, 3 cases had pressure ulcers recur due to improper nursing, while the rest of the patients had tissue flaps with good appearance and soft texture and no recurrence of pressure ulcers.Conclusions:Based on the characteristics of wound shape, size, and depth after debridement of stage Ⅳ pressure ulcers in the sacrococcygeal region, individualized selection of flap, myocutaneous flap, or a combination of flap and gluteus maximus muscle flap based on the perforating branch of the superior gluteal artery perforator can achieve good clinical repair results. The postoperative tissue flap survived well, with a good appearance, soft texture, and less recurrence of pressure ulcers.

OBJECTIVE: To explore weight-bearing stability of Pilon fracture fixed by external fixator. METHODS: Six ankle bone models (right side) and 4 pairs (8 ankle cadaver specimens) were selected. Pilon fracture model was prepared by using the preset osteotomy line based on Ruedi Allgower Pilon fracture type. Pilon fracture model was built by using a minimally invasive osteotomy. After ankle bone model and cadaver specimen model were fixed with external fixator, axial load was carried out on mechanical loading machine. After ankle bone model and cadaver specimen model were fixed with external fixator, axial load was carried out on mechanical loading machine. Axial loads of 150, 300 and 450 N were applied to ankle bone model, and displacements of fibula fracture blocks, lateral tibia fracture blocks and medial tibia fracture blocks in three-dimensional space (X, Y and Z axes) were recorded by dynamic capture instrument. Axial loads of 300, 600 and 900 N were applied to ankle cadaver model fixed by external fixator. X-ray films of Pilon fracture cadaver model fixed by external fixator under different loading conditions were taken. The anterior tibial angle, tibial malleolar point angle, talus shift value, talus tilt angle, lateral malleolar shift value, lateral malleolar shift value, medial malleolar separation shift value and articular surface step displacement value were measured under different loads by digimizer software. RESULTS: After 150, 300 and 450 N axial loads were applied to Pilon fracture models fixed by external fixator, no loosening or fracture of external fixator was observed, and no loosening, fracture or irreversible plastic deformation of Kirschner needle were observed. The displacement values of fibular fracture pieces on X-axis(around) were 0.032 (-0.022, 0.269), 0.061 (-0.002, 0.427), 0.212(-0.016, 1.223) mm, and the displacement values on Y-axis(above and below) were 0.002(-0.031, 0.103), 0.051(-1.133, 0.376), 0.128 (-1.394, 0.516) mm, and displacement values on Z-axis (front and rear) were -0.003 (-0.130, 0.171), 0.137 (-0.076, 0.433), 0.030(-0.487, 0.478) mm;the displacement values of lateral tibial fractures on X-axis were 0.000(-0.108, 0.027), 0.083(-0.364, 0.050), -0.121(-0.289, 0.165) mm, and displacement values on Y-axis were -0.009(-0.200, 0.025), -0.179(-0.710, 0.084), -0.257(-0.799, 0.027) mm, and displacement values on Z-axis were 0.112(-0.024, 0.256), 0.157(-0.068, 0.293), -0.210(-0.035, 0.430) mm;the displacement values of medial tibial fracture block on X-axis were -0.010(-0.060, 0.013), -0.165(-0.289, 0.056), -0.181(-0.395, 0.013) mm, and the displacement values on Y-axis were -0.036(-0.156, 0.007), -0.104(-0.269, 0.178), -0.245(-0.380, -0.011) mm, and displacement values on Z-axis were -0.005(-0.372, 0.189), -0.012 (-1.774, 0.380), 0.200 (-1.963, -0.540) mm. After 300, 600 and 900 N axial loads were applied to Pilon fracture cadaverous models fixed with external fixators, there were no significant difference in anterior tibial angles, angles of malleolar points of tibia, oblique angles of talus, fracture steps, shift values of talus, lateral shift values of lateral malleolus, lateral shift values of medial malleolus, lateral shift values of medial malleolus between under different loading conditions and those without loading (P>0.05). No loosening or fracture of external fixator as a whole, loosening, fracture or irreversible deformation of Kirschner needle at the local fixed fracture end occurred. CONCLUSION The early weight-bearing external fixator could maintain stability of fracture end and ankle joint, and the maximum weight is not more than 300 N. In clinical practical application, material characteristics of the implant and type of fracture should be selected.
Humans ; Weight-Bearing ; Biomechanical Phenomena ; External Fixators ; Tibial Fractures/physiopathology* ; Fracture Fixation/instrumentation* ; Male

Based on the literature study,the thoughts and possible therapeutic mechanism in treating male infertility from the perspective of spleen and kidney by regulating intestinal flora were explored.Disturbance of intestinal flora is one of the important factors leading to the development of male infertility,and the spleen and kidney have certain similarities to intestinal flora in the physiological function and pathological changes.Moreover,tonifying the kidney and strengthening the spleen can regulate the intestinal flora by fostering the growth of beneficial bacteria,inhibiting the reproduction of pathogenic bacteria,and protecting the barrier of the intestinal mucosa.Therefore,the possible therapeutic mechanisms in treating male infertility with the prescriptions for tonifying the kidney and strengthening the spleen to regulate intestinal flora are as follows:inhibiting the expression of inflammatory factors to reduce the inflammatory reaction of testicular tissues;improving the antioxidant capacity to alleviate the damage of spermatozoa caused by oxidative stress,and improving the bad mood to alleviate the impact of psychological stress on the reproductive system.The exploration of the thoughts for treating male infertility from the perspective of spleen and kidney by regulating intestinal flora may provide a new entry point for modern Chinese medicine clinical treatment of male infertility.

Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of Rhei Radix et Rhizoma and Coptidis Rhizoma was explored. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used to characterize the morphological differences of Rhubarb single decoction, Coptis single decoction and Rhubarb and Coptis co-decoction. An in vitro antibacterial model (E. coli, E. faecium and B. subtilis) was established to evaluate the damage effect of the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma on enterobacteria. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the changes of chemical components of single decoctions and co-decoctions. The co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma was turbid after decocting. The spherical particles of 300-400 nm were observed under SEM, and the co-decoction was more uniform and stable than that of single decoction. The interaction between supramolecules formed after the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma and enterobacteria was significantly different from that of single decoction. In the process of interaction between supramolecules and enterobacteria, the spherical state was maintained, and the medicinal ingredients in Coptidis Rhizoma or Rhei Radix et Rhizoma were blocked, which could effectively alleviate the damage to enterobacteria. This study provided a reference for subsequent studies on the regulation of intestinal flora homeostasis by the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

The effect of different concentrations of glycyrrhizic acid (GA) and Zn²⁺ on the self-assembly of metal complexes was investigated by forming metal complexes, and the properties and assembly mechanisms of the formed carrier-free supramolecular hydrogel were characterised. Scanning electron microscopy (SEM) and zeta potential were used to characterise the microscopic morphology and stability of the GA-Zn complex hydrogel, which had spherical-like particles of about 1 μm with good stability; the rheometer was used to detect its materialistic properties, which showed excellent stability, self-healing property and reversibility; through in vitro bacterial inhibition, it was found that the GA-Zn carrier-free supramolecular hydrogel has enhanced bacterial inhibition function after assembly. The hydrogel was also found to possess both anti-inflammatory and antioxidant efficacy when evaluated using LPS and H₂O₂ induced RAW 264.7 cell damage models, respectively. The above results suggest that GA-Zn hydrogel not only has good materialistic properties, but also possesses good antibacterial, anti-inflammatory and antioxidant activities, which has the value of clinical research as a carrier-free multi-functional antimicrobial dressing, and the present study provides a reference for the discovery of novel biomedical materials from active molecules of natural traditional Chinese medicine.