ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

Multiple myeloma(MM)is a malignant plasma cell clonal disease and the second most common malignant tumor of the blood system,accounting for approximately 1%of all tumor diseases and 13%of hematologic cancers.In recent years,its incidence has shown an upward trend.The development of proteasome inhibitors(PIs),immunomodulatory drugs(IMiDs),and autologous hematopoietic stem cell transplantation(auto-HSCT)has greatly improved the efficacy and prognosis of patients with myeloma.Among these,the development and clinical application of PIs represents a major milestone.However,long-term clinical experiencehas revealed that patients with MM who used PIs may develop new heart diseases,such as hypertension,cardiac insufficiency,arrhythmia,and ischemic heart disease,especially those who used cafilzomib.The use of PIs increases the probability of adverse cardiovascular events(CVAEs).Owing to the significant heterogen-eity in the definition of cardiotoxic endpoints,the exclusion of high-risk patients in clinical trials and the detection and treatment of PI-re-lated CVAEs vary.Therefore,the lack of sufficient evidence-based medical data hinders the standardized diagnosis and treatment of PI-re-lated CVAEs.This review summarizes the relevant mechanisms and response measures of cardiovascular diseases induced by PIs.

Objective:To evaluate spinal-pelvic mobility and sagittal spinal-pelvic alignment characteristics in patients with developmental dysplasia of the hip (DDH), and to investigate differences in sagittal spinal-pelvic parameters between patients with DDH and those with osteonecrosis of the femoral head (ONFH).Methods:A total of 55 patients with DDH who underwent primary total hip arthroplasty (THA) at the Affiliated Hospital of Xuzhou Medical University between April 2021 and March 2024 were retrospectively analyzed. The cohort included 8 males and 47 females, with a mean age of 56.16±10.82 years (range: 26-76 years). Among them, 18 patients had bilateral DDH and 37 had unilateral DDH. Fifty-five age- and sex-matched patients with ONFH were selected as the control group. Unilateral DDH cases were classified according to the Hartofilakidis classification: 18 cases of type A, 13 cases of type B, and 6 cases of type C. Lateral spinal-pelvic radiographs were used to measure pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and lumbar lordosis (LL) in both standing and sitting positions. Changes in sagittal spinal-pelvic parameters between standing and sitting positions were analyzed to assess spinal-pelvic mobility. Spinal-pelvic mobility was considered abnormal if △SS was outside the range of 10°-30°. Abnormal mobility was further categorized as stiffness (△SS<10°) or hypermobility (△SS>30°).Results:The PI (52.37°±12.43°), standing PT (12.13°±9.50°), and sitting PT (36.49°±13.43°) of DDH patients were significantly higher than those of ONFH patients (44.88°±11.38°, 7.80°±11.36°, and 28.91°±11.38°, respectively), with statistically significant differences ( P<0.05). Abnormal spinal-pelvic mobility, including both stiffness and hypermobility, was observed in 53% of DDH patients, with stiffness accounting for 20%. These proportions were significantly higher than those in ONFH patients, which were 24% and 6%, respectively ( P<0.05). The prevalence of abnormal spinal-pelvic mobility in Hartofilakidis type C DDH patients was 83%, significantly higher than the 30.8% observed in type B patients (χ 2=4.550, P=0.033). The standing LL (54.37°±11.59°) and sitting LL (28.56°±15.51°) in unilateral DDH patients were significantly greater than those in bilateral DDH patients (46.88°±15.30° and 20.42°±9.77°, respectively), with statistically significant differences ( P< 0.05). Conclusions:Compared with patients with ONFH, those with DDH demonstrate a higher prevalence of abnormal spinal-pelvic mobility, particularly a greater incidence of spinal stiffness. Among DDH subtypes, Hartofilakidis type C patients exhibit a higher proportion of abnormal mobility compared to types A and B. Additionally, patients with unilateral DDH present with greater lumbar lordosis than those with bilateral involvement.

Objective:To evaluate spinal-pelvic mobility and sagittal spinal-pelvic alignment characteristics in patients with developmental dysplasia of the hip (DDH), and to investigate differences in sagittal spinal-pelvic parameters between patients with DDH and those with osteonecrosis of the femoral head (ONFH).Methods:A total of 55 patients with DDH who underwent primary total hip arthroplasty (THA) at the Affiliated Hospital of Xuzhou Medical University between April 2021 and March 2024 were retrospectively analyzed. The cohort included 8 males and 47 females, with a mean age of 56.16±10.82 years (range: 26-76 years). Among them, 18 patients had bilateral DDH and 37 had unilateral DDH. Fifty-five age- and sex-matched patients with ONFH were selected as the control group. Unilateral DDH cases were classified according to the Hartofilakidis classification: 18 cases of type A, 13 cases of type B, and 6 cases of type C. Lateral spinal-pelvic radiographs were used to measure pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and lumbar lordosis (LL) in both standing and sitting positions. Changes in sagittal spinal-pelvic parameters between standing and sitting positions were analyzed to assess spinal-pelvic mobility. Spinal-pelvic mobility was considered abnormal if △SS was outside the range of 10°-30°. Abnormal mobility was further categorized as stiffness (△SS<10°) or hypermobility (△SS>30°).Results:The PI (52.37°±12.43°), standing PT (12.13°±9.50°), and sitting PT (36.49°±13.43°) of DDH patients were significantly higher than those of ONFH patients (44.88°±11.38°, 7.80°±11.36°, and 28.91°±11.38°, respectively), with statistically significant differences ( P<0.05). Abnormal spinal-pelvic mobility, including both stiffness and hypermobility, was observed in 53% of DDH patients, with stiffness accounting for 20%. These proportions were significantly higher than those in ONFH patients, which were 24% and 6%, respectively ( P<0.05). The prevalence of abnormal spinal-pelvic mobility in Hartofilakidis type C DDH patients was 83%, significantly higher than the 30.8% observed in type B patients (χ 2=4.550, P=0.033). The standing LL (54.37°±11.59°) and sitting LL (28.56°±15.51°) in unilateral DDH patients were significantly greater than those in bilateral DDH patients (46.88°±15.30° and 20.42°±9.77°, respectively), with statistically significant differences ( P< 0.05). Conclusions:Compared with patients with ONFH, those with DDH demonstrate a higher prevalence of abnormal spinal-pelvic mobility, particularly a greater incidence of spinal stiffness. Among DDH subtypes, Hartofilakidis type C patients exhibit a higher proportion of abnormal mobility compared to types A and B. Additionally, patients with unilateral DDH present with greater lumbar lordosis than those with bilateral involvement.

Multiple myeloma(MM)is a malignant plasma cell clonal disease and the second most common malignant tumor of the blood system,accounting for approximately 1%of all tumor diseases and 13%of hematologic cancers.In recent years,its incidence has shown an upward trend.The development of proteasome inhibitors(PIs),immunomodulatory drugs(IMiDs),and autologous hematopoietic stem cell transplantation(auto-HSCT)has greatly improved the efficacy and prognosis of patients with myeloma.Among these,the development and clinical application of PIs represents a major milestone.However,long-term clinical experiencehas revealed that patients with MM who used PIs may develop new heart diseases,such as hypertension,cardiac insufficiency,arrhythmia,and ischemic heart disease,especially those who used cafilzomib.The use of PIs increases the probability of adverse cardiovascular events(CVAEs).Owing to the significant heterogen-eity in the definition of cardiotoxic endpoints,the exclusion of high-risk patients in clinical trials and the detection and treatment of PI-re-lated CVAEs vary.Therefore,the lack of sufficient evidence-based medical data hinders the standardized diagnosis and treatment of PI-re-lated CVAEs.This review summarizes the relevant mechanisms and response measures of cardiovascular diseases induced by PIs.

Objective:To investigate the effects of acetabular cup positions on the acetabular side stress in hip dysplasia after total hip arthroplasty (THA) using finite element analysis.Methods:Data were obtained from a 36-year-old female patient with developmental dysplasia of the hip. Three-dimensional finite element models were established for different acetabular cup positions using finite element analysis. Each model was categorized based on the center of rotation into four groups: anatomical rotation center, high rotation center, lateralized rotation center, superior-lateral rotation center. ANSYS software applied loads to the model to simulate the stress around the acetabulum in standing (588 N vertical stress) and walking conditions ( X=325 N, Y=-195 N, Z=1 462.5 N). Quantitative analyses of the relative displacement and stress at the acetabular-bone interface were conducted for each region under the two different loading conditions in all eight models. Results:In the standing position with a cup coverage of 90%, the relative displacement at the acetabular-bone interface was: 45.16 μm for the anatomical rotation center group, 47.57 μm for the high rotation center group, 77.27 μm for the lateralized rotation center group, and 96.13 μm for the superior-lateral rotation center group. Acetabular stress values were 9.07 MPa for the anatomical rotation center group, 11.23 MPa for the high rotation center group, 10.88 MPa for the lateralized rotation center group, and 17.75 MPa for the superior-lateral rotation center group. With a cup coverage of 70%, the relative displacements were 64.15, 65.71, 104.10, and 144.53 μm for the respective groups. The corresponding stresses were 9.30, 11.31, 13.98, and 21.45 MPa. In the walking state with a cup coverage of 90%, the relative displacements at the acetabular-bone interface were 189.67 μm for the anatomical rotation center group, 173.55 μm for the high rotation center group 311.03 μm for the lateralized rotation center group, and 572.93 μm for the superior-lateral rotation center group. The stresses were 39.92, 37.33, 47.92, and 71.94 MPa, respectively. With a cup coverage of 70%, the relative displacements were 239.09 μm for the anatomical rotation center group, 248.83 μm for the high rotation center group, 381.84 μm for the lateralized rotation center group, and 1105.90 μm for the superior-lateral rotation center group. The corresponding stresses were 40.62, 58.42, 56.26, and 3,606.30 MPa.Conclusion:With cup coverage at 70% and 90%, the high rotation center and anatomical rotation center exhibited lower and less frequent relative displacements at the acetabular-bone contact surface.

The establishment of mother-infant bonding is closely related to maternal mental health and early growth and development of infants. This paper reviews the concept, evaluation tools, influencing factors and intervention measures of maternal-infant bonding, in order to provide a basis for promoting the normal establishment of postpartum maternal infant relationships and maternal infant health.

Objective:To investigate the clinical characteristics, risk factors, and prognosis of invasive pulmonary aspergillosis (IPA) in patients with dermatomyositis associated with positive anti-melanoma differentiation-associated gene 5 (MDA5-DM).Methods:A total of 55 patients with MDA5-DM were analyzed. Patients were divided into IPA (+) group (14 cases) and IPA (-) group (41 cases) based on the presence of IPA. Microbiological examination and clinical data were analyzed. Risk factor analysis was performed using Binary Logistic regression, and survival analysis was carried out using Kaplan-Meier method.Results:Aspergillus flavus (5/14, 35.7%) and Aspergillus fumigatus (4/14, 28.6%) were the most common species in MDA5-DM patients with IPA. Compared to the IPA (-) group, IPA (+) group had higher serum level of α-hydroxybutyrate dehydrogenase (246 U/L vs. 191 U/L, Z=-2.02, P=0.043) and ferritin [1 306.7(518.7, 2 977.8)ng/ml vs. 472.6(269.0, 792.1)ng/ml, Z=-2.09, P=0.036], lower CD8 + T lymphocyte counts {[111.5 (68.3, 214.0)]×10 6/L vs. [188.0(141.0, 270.0)]×10 6/L, Z=-2.18, P=0.029}, and more positive BALF GM tests [70.0%(7/10) vs. 18.9%(7/37), χ2=9.82, P=0.004]. Elevated serum ferritin was found to be an independent risk factor for IPA occurrence [adjusted OR (95% CI)=1.001 (1.000, 1.002), P=0.031)]. In addition, the 6-month cumulative survival rate was significantly lower in the IPA (+) group than in the IPA (-) group (78.6% vs. 97.6%, P=0.021). Conclusion:The mortality of MDA5-DM patients is increased after IPA infection. Elevated serum ferritin is an independent risk factor for IPA occurrence, and active prevention and treatment of IPA are expected to improve the prognosis of patients.

Objective To explore the therapeutic mechanism of Liangxue Tongyu Prescription in the treatment of acute Intracerebral hemorrhage by studying the target of Liangxue Tongyu Prescription on circRNAand possible related signaling pathways in Spontaneously hypertensive rats(SHR)in the acute stage of Intracerebral hemorrhage.Methods The SHR was divided into model group,experimental group and blank group.Intracerebral hemorrhage models were performed in model group and experimental group,the neurological deficits of SHR were scored.The experimental group was given Liangxue Tongyu Prescription for 5 days,the model group and the blank group were given equal doses of normal saline for 5 days each.The circRNA in the three groups of SHR brain tissue samples were detected by high-throughput sequencing technology,and the significantly different circRNAs were analyzed by Cluster Analysis,Go and KEGG enrichment analysis.Real-time fluorescence quantitative polymerase chain reaction(RT-PCR)was used to verify the expressions of the top 5 significantly different circRNAwith fold change.The significantly differentially expressed circRNA were transformed into human homologous genes,and combined with the treatment targets selected by our research group in the early stage of Intracerebral hemorrhage,the intersection targets were input into Cytoscape software to construct the traditional Chinese medicines-components-targets-pathways network.Results The results of sequencing showed that there were 150 significantly different circRNA,including 60 up-regulated circRNAand 90 down-regulated circRNA.RT-PCR verification results showed that the expression trends of the top 5 circRNA were consistent with the high-throughput sequencing results.Network pharmacology results show that multiple active ingredients in six traditional Chinese medicines including Radix Paeoniae Rubra,Rheum officinale,Rehmannia glutinosa,Paeonia suffruticosa,Acorus tatarinowii and Panax notoginseng in Liangxue Tongyu Prescription correspond to the acute phase treatment target PRKCA of Intracerebral hemorrhage,which is the parent gene of CIRI_circ_10530.Among 849 GO enrichment entries,the parent gene of CIRI_circ_10530 was distributed in 209 GO terms;Among 149 KEGG signal pathways,the parent gene of CIRI_circ_10530 was distributed in 62 signal pathways.And Rheum officinale is the important Chinese medicine in Liangxue Tongyu Prescription for the treatment of acute Intracerebral hemorrhage.Kaempferol,emodin and quercetin are important active components of the pharmacodynamic mechanism of Liangxue Tongyu Prescription.Conclusion The mechanism of Liangxue Tongyu Prescription in the acute phase of Intracerebral hemorrhage may be related to the activation of PRKCA by kaempferol,quercetin,emodin and other key active ingredients,and the regulation of PKC affecting its key signaling pathways.

Objective To explore the therapeutic mechanism of Liangxue Tongyu Prescription in the treatment of acute Intracerebral hemorrhage by studying the target of Liangxue Tongyu Prescription on circRNAand possible related signaling pathways in Spontaneously hypertensive rats(SHR)in the acute stage of Intracerebral hemorrhage.Methods The SHR was divided into model group,experimental group and blank group.Intracerebral hemorrhage models were performed in model group and experimental group,the neurological deficits of SHR were scored.The experimental group was given Liangxue Tongyu Prescription for 5 days,the model group and the blank group were given equal doses of normal saline for 5 days each.The circRNA in the three groups of SHR brain tissue samples were detected by high-throughput sequencing technology,and the significantly different circRNAs were analyzed by Cluster Analysis,Go and KEGG enrichment analysis.Real-time fluorescence quantitative polymerase chain reaction(RT-PCR)was used to verify the expressions of the top 5 significantly different circRNAwith fold change.The significantly differentially expressed circRNA were transformed into human homologous genes,and combined with the treatment targets selected by our research group in the early stage of Intracerebral hemorrhage,the intersection targets were input into Cytoscape software to construct the traditional Chinese medicines-components-targets-pathways network.Results The results of sequencing showed that there were 150 significantly different circRNA,including 60 up-regulated circRNAand 90 down-regulated circRNA.RT-PCR verification results showed that the expression trends of the top 5 circRNA were consistent with the high-throughput sequencing results.Network pharmacology results show that multiple active ingredients in six traditional Chinese medicines including Radix Paeoniae Rubra,Rheum officinale,Rehmannia glutinosa,Paeonia suffruticosa,Acorus tatarinowii and Panax notoginseng in Liangxue Tongyu Prescription correspond to the acute phase treatment target PRKCA of Intracerebral hemorrhage,which is the parent gene of CIRI_circ_10530.Among 849 GO enrichment entries,the parent gene of CIRI_circ_10530 was distributed in 209 GO terms;Among 149 KEGG signal pathways,the parent gene of CIRI_circ_10530 was distributed in 62 signal pathways.And Rheum officinale is the important Chinese medicine in Liangxue Tongyu Prescription for the treatment of acute Intracerebral hemorrhage.Kaempferol,emodin and quercetin are important active components of the pharmacodynamic mechanism of Liangxue Tongyu Prescription.Conclusion The mechanism of Liangxue Tongyu Prescription in the acute phase of Intracerebral hemorrhage may be related to the activation of PRKCA by kaempferol,quercetin,emodin and other key active ingredients,and the regulation of PKC affecting its key signaling pathways.