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.

BACKGROUND:Arthroscopic single-row fixation with knotless suture bridge fixation techniques have been commonly used in the treatment of rotator cuff injuries,but the clinical efficacy in rotator cuff injuries combined with osteoporosis is unclear.OBJECTIVE:To investigate the clinical efficacy of arthroscopic single-row fixation versus knotless suture bridge fixation in the treatment of rotator cuff injuries combined with osteoporosis.METHODS:One hundred and twenty-two patients with rotator cuff injuries combined with osteoporosis who underwent arthroscopic treatment admitted to Affiliated Hospital of Xuzhou Medical University between January 2018 and August 2022 were retrospectively analyzed.They were divided into two groups according to the treatment plan.There were 63 patients with single-row fixation(single-row group)and 59 patients with knotless suture-bridge fixation(suture-bridge group).The visual analog scale scores for pain,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley score,and shoulder range of motion were compared between the two groups at the preoperative and 1 year postoperative periods.Rotator cuff re-tears were evaluated at 1 year postoperatively using the Sugaya staging criteria.The occurrence of complications was recorded in both groups.RESULTS AND CONCLUSION:(1)All patients received more than 1-year follow-up.No complications such as incision infection and nerve injury occurred in both groups after surgery.(2)Postoperative visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were significantly improved 1 year postoperatively in both groups compared with the preoperative period(P＜0.05).Visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were better in the suture-bridge group than in the single-row group 1 year postoperatively(P＜0.05).(3)At 1 year postoperatively,the re-tear rate in the single-row group[22％(14/63)]was significantly higher than that in the suture-bridge group[7％(4/59)],and the difference between the two groups was statistically significant(x2=5.777,P=0.016).(4)It is indicated that arthroscopic single-row fixation and knotless suture bridge fixation for rotator cuff injuries combined with osteoporosis both yielded satisfactory clinical outcomes,but knotless suture bridge fixation was more clinically effective,with a lower rate of postoperative retear.

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.

BACKGROUND:Arthroscopic single-row fixation with knotless suture bridge fixation techniques have been commonly used in the treatment of rotator cuff injuries,but the clinical efficacy in rotator cuff injuries combined with osteoporosis is unclear.OBJECTIVE:To investigate the clinical efficacy of arthroscopic single-row fixation versus knotless suture bridge fixation in the treatment of rotator cuff injuries combined with osteoporosis.METHODS:One hundred and twenty-two patients with rotator cuff injuries combined with osteoporosis who underwent arthroscopic treatment admitted to Affiliated Hospital of Xuzhou Medical University between January 2018 and August 2022 were retrospectively analyzed.They were divided into two groups according to the treatment plan.There were 63 patients with single-row fixation(single-row group)and 59 patients with knotless suture-bridge fixation(suture-bridge group).The visual analog scale scores for pain,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley score,and shoulder range of motion were compared between the two groups at the preoperative and 1 year postoperative periods.Rotator cuff re-tears were evaluated at 1 year postoperatively using the Sugaya staging criteria.The occurrence of complications was recorded in both groups.RESULTS AND CONCLUSION:(1)All patients received more than 1-year follow-up.No complications such as incision infection and nerve injury occurred in both groups after surgery.(2)Postoperative visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were significantly improved 1 year postoperatively in both groups compared with the preoperative period(P＜0.05).Visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were better in the suture-bridge group than in the single-row group 1 year postoperatively(P＜0.05).(3)At 1 year postoperatively,the re-tear rate in the single-row group[22％(14/63)]was significantly higher than that in the suture-bridge group[7％(4/59)],and the difference between the two groups was statistically significant(x2=5.777,P=0.016).(4)It is indicated that arthroscopic single-row fixation and knotless suture bridge fixation for rotator cuff injuries combined with osteoporosis both yielded satisfactory clinical outcomes,but knotless suture bridge fixation was more clinically effective,with a lower rate of postoperative retear.

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 application effects of cardiac resynchronization therapy(CRT)of[left bundle optimization(LOT)]and biventricular pacing(BiV)in the patients with chronic heart failure complicating left bundle branch block.Methods The single center,prospective and non-randomized controlled study method was used.Forty-two patients with heart failure meeting CRT in this center from April 2020 to April 2022 were consecutively included.Among them,32 cases adopted the BiV-CRT(BiV-CRT group)and 10 cases adopted LOT-CRT(LOT-CRT group).The pacing-making parameters,quality of life scale(SF-36)score,6-min walk test(6-MWT),ECG QRS width(QRSd),left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF)and New York cardiac function grade(NYHA)situation were collected before surgery,after surgery immediately and in postoperative 3,6,12 months.Their complica-tions and clinical outcomes were evaluated.Results The pacing threshold value in the LOT-CRT group was stable and lower than that in the BiV-CRT group(P＜0.05);QRSd in postoperative 12 months in the LOT-CRT group was shorter than that in the BiV-CRT group[(115.0±14.3)ms vs.(133.0±14.0)ms,P＜0.05]and 6-MWT was longer than that in the BiV-CRT group[(327.0±52.8)m vs.(274.0±52.8)m,P＜0.05],and the differences were statistically significant(P＜0.05);LVEF,LVEDD,NYHA cardiac grade and SF-36 score in postoperative 12 months were improved compared with those before implantation.The rehospitaliza-tion rate of heart failure in the LOT-CRT group was lower.Conclusion LOT-CRT could obtain a narrower QRS wave and longer 6-MWT than BiV-CRT.

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 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.

Objective:To investigate the difference in the efficacy of extended trochanteric osteotomy (ETO) and subtrochanteric shortening osteotomy (SSO) in total hip arthroplasty (THA) for Crowe type IV developmental dysplasia of the hip (DDH).Methods:Forty patients (51 hips) who underwent primary THA for Crowe type IV DDH from April 2012 to August 2020 at the First Affiliated Hospital of Soochow University and the Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. The patients were classified into ETO (extended greater trochanteric osteotomy) group and SSO(subtrochanteric shortening osteotomy) group. There were 12 patients (14 hips) in the ETO group, with 3 males and 9 females, aged 49.9±16.7 years old (range, 22-75 years old) and 28 patients (37 hips) in the SSO group, with 7 males and 21 females, aged 50.3±14.0 years (range, 22-76 years). In both groups, Harris hip score (HHS), leg length discrepancy, limp, Trendelenburg sign were used to evaluate the functional results and anteroposterior radiographs of the pelvis were taken at each follow-up to assess bone healing at the osteotomy site, periprosthetic osteolysis, bone ingrowth and periprosthetic loosening. Complications were recorded and analyzed.Results:All 51 hips were followed up for at least 24 months. The operative time and total blood loss was 116.8±14.2 vs. 128.3±19.2 min and 650.8±191.4 vs. 808.3±151.3 ml in the ETO group and the SSO group with significant difference ( t=2.04, P=0.047; t=3.08, P=0.003) respectively. At the follow-up of 24 months the HHS of ETO and SSO groups were 94.8±6.3 vs. 93.9±4.9 points and the leg length discrepancy was 4.6±2.2 vs. 5.2±3.0 mm. The positive rate of Trendelenburg's sign was 7% vs. 16% and the incidence of limp was 17% vs. 29% in the ETO group and the SSO group with no significant difference ( t=0.54, P=0.591; t=0.68, P=0.499; P=0.657; P=0.693). The length of femoral shortening in the ETO group and SSO group was 30.8±4.1 vs 35.3±7.9 mm with significant difference ( t=2.02, P=0.049). Time for bone healing at the osteotomy site was 5.8±1.5 vs. 6.0±1.4 months and the incidence of intraoperative femoral fractures was 36% and vs. 65% with no significant difference ( t=0.45, P=0.657; χ 2=3.52, P=0.061). Bone in-growth (or bone on-growth) fixation was obtained for all acetabular and femoral prostheses, with no hips of prosthesis displacement, periprosthetic osteolysis, or dislocation. Conclusion:Total hip arthroplasty for Crowe type IV DDH can achieve satisfactory clinical efficacy with similar functional recovery and rate of complication in extended trochanteric osteotomy and subtrochanteric shortening osteotomy. However, the extended greater trochanter osteotomy can reduce the operation time, blood loss and length of femoral shortening.