Objective:To investigate the efficacy and safety of daratumumab (Dara) - combination regimens for newly diagnosed multiple myeloma (NDMM).Methods:A retrospective case series study was conducted. The clinical data of 34 patients with NDMM receiving treatment regimen including Dara from Qilu Hospital of Shandong University, Yantai Yuhuangding Hospital, Huangdao Branch of Affiliated Hospital of Qingdao University and Taian City Central Hospital between April 2020 and March 2022 were retrospectively collected. The efficacy, survival and adverse reactions of patients were analyzed. Cox proportional risk model was used to analyze the factors affecting overall survival (OS) and minimal residual disease (MRD) turning negative.Results:Among 34 patients with NDMM, there were 19 males and 15 females, with 21 cases aged < 65 years and 13 cases aged ≥65 years. The median follow-up duration [ M ( Q1, Q3)] was 22 months (19 months, 26 months), the median of Dara treatment cycles was 7 (5, 11), and the overall response rate (ORR) reached 97.1% (33/34). There were statistically significant differences in the optimal efficacy of patients stratified by receiving hematopoietic stem cell transplantation or not and receiving different treatment cycles (all P ≤ 0.05), while there were no statistically significant differences in patients stratified by other clinical features (all P > 0.05). The 1-year progression-free survival rate was 79.4% and the 1-year OS rate was 94.1%. Multivariate Cox regression analysis showed that the cycle number of treatment regimens containing Dara was an independent influencing factor of MRD turning negative (6 cycles vs. 2 cycles, HR = 0.267, 95% CI: 0.076-0.935, P = 0.039); age ≥ 65 years was an independent risk factor for OS ( HR = 35.313, 95% CI: 1.709-729.669, P = 0.021). The incidence of hematological adverse reactions grade 3 or above was 20.6% (7/34), and the non-hematological adverse reactions primarily included infection [44.1% (15/34)] and edema of extremity and trunk [41.2% (14/34)]. Conclusions:The Dara-based regimens for NDMM exhibit a high ORR. The remission depth accelerated with the increasing number of treatment cycle, and the adverse reactions are mild.

In case of hepatic ischemia-reperfusion injury(HIRI),mitophagy is induced by multiple pathways such as PINK1/Parkin and mitophagy receptor,which is closely related to mitochondrial dynamic related protein.Mito-phagy is a double-edged sword.Moderate mitophagy is effective in reducing the oxidative stress and maintaining mi-tochondria homeostasis,thereby reducing hepatocyte apoptosis and necrosis,inhibiting inflammation response and mitigating HIRI.However excessive mitophagy will aggravate HIRI.So research on the role and mechanism of mito-phagy may facilitate the development of new strategy for prevention and clinical treatment of HIRI.

Objective:To explore the influence of deviation of the bolt in femoral neck system (FNS) on the short-term outcomes in young and middle-aged patients with displaced femoral neck fracture.Methods:A retrospective analysis was conducted of the 114 young and middle-aged patients with displaced femoral neck fracture who had been treated with FNS at Department of Orthopaedics, Suzhou Municipal Hospital from December 2019 to January 2023. Based on the postoperative measurements of the deviation of the bolt tip to the central axis of the femoral head and neck (W), the patients were divided into a central group (W≤20%) and a deviation group (W>20%). In the central group of 63 cases, there were 27 males and 36 females with a mean age of (46.4±8.0) years. In the deviation group of 51 cases, there were 20 males and 31 females with a mean age of (45.1±9.8) years. The 2 groups were compared in terms of weight-bearing time, fracture healing time, tip-apex distance, degree of femoral neck shortening, Harris Hip Score and EuroQol five-dimensional questionnaire-5L (EQ-5D-5L) utility value at the last follow-up, as well as complications and revision surgeries.Results:There was no statistically significant difference in the preoperative general information, auxiliary reduction or quality of fracture reduction between the 2 groups, showing comparability between groups ( P>0.05). There was no significant difference in the partial weight-bearing time between the 2 groups ( P>0.05). In the central group, the full weight-bearing time [15.0 (14.0, 16.0) weeks] and fracture healing time [14.0 (12.0, 15.0) weeks] were significantly shorter than those in the deviation group [16.0 (15.0, 19.0) weeks; 15.0 (13.0, 17.0) weeks], the tip-apex distance [(21.4±3.4) mm] was significantly shorter than that in the deviation group [(23.5±2.7) mm], the Harris Hip Score [(90.6±6.1) points] and EQ-5D-5L utility value [0.9 (0.8, 0.9)] at the last follow-up were significantly higher than those in the deviation group [(87.7±6.2) points; 0.9 (0.8, 0.9)], and the incidences of moderate and severe femoral neck shortening [25.4% (16/63)], avascular necrosis of the femoral head [0 (0/63)] and revision surgery [0 (0/63)] were significantly lower than those in the deviation group [66.7% (34/51), 7.8% (4/51), 9.8% (5/51)] (all P< 0.05). Conclusion:A closer positioning of the FNS bolt to the central axis of the femoral head and neck favors satisfactory short-term outcomes and a lower revision surgery rate in young and middle-aged patients with displaced femoral neck fracture.

Objective To analyze the effects of immediate multi-vessel percutaneous coronary inter-vention(MV-PCI)and staged vascular intervention(Staged-PCI,immediate PCI for culprit-only followed by a delayed treatment of all other lesions)on the prognosis in elderly patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 417 elderly acute STEMI patients who underwent PCI in Baoding First Central hospital from January 2021 to June 2023 were enrolled,and according to different treatment strategies,they were divided into MV-PCI group(87 cases)and Staged-PCI group(330 cases).A propensity score matching(PSM)model was established based on baseline data of the two groups,there were 84 cases in each group.During a mean follow-up period of 13.5 months,with the occurrence of main adverse cardi-ovascular and cerebrovascular events(MACCE)as endpoint,the incidence of MACCE was com-pared between the two groups after PSM.Cox proportional hazard regression model was used to analyze the risk factors of MACCE.Results Before PSM,there were significant differences be-tween the two groups in terms of age,proportions of hypertension,diabetes and hyperlipidemia,family history,stroke history,peripheral artery disease,preoperative SBP,lesion vessels(such as left anterior descending branch and left circumflex branch),and number of non-diseased vessels(P＜0.05).Kaplan-Meier survival curve showed that the incidences of MACCE and all-cause mor-tality were significantly lower in the MV-PCI group than the Staged PCI group(Plog rank＜0.05).Multivariate Cox proportional hazard regression model showed that MV-PCI was a protective prognostic factor for MACCE(HR=0.263,95％CI:0.105-0.659,P=0.004)and all-cause death(HR=0.236,95％CI:0.007-0.722,P=0.016).Conclusion MV-PCI can significantly improve the prognosis of elderly patients with acute STEMI with multivessel disease.

BACKGROUND: Recent studies have shown that induced pluripotent stem cells (iPSCs) could be differentiated into mesenchymal stem cells (MSCs) with notable advantages over iPSCs per se. In order to promote the application of iPSC-MSCs for osteoregenerative medicine, the present study aimed to assess the ability of murine iPSC-MSCs to differentiate into osteoblast phenotype. METHODS: Osteogenic differentiation medium, blending mouse osteoblast-conditioned medium (CM) with basic medium (BM) at ratio 3:7, 5:5 and 7:3, were administered to iPSC-MSCs, respectively. After 14 days, differentiation was evaluated by lineage-specific morphology, histological stain, quantitative reverse transcription-polymerase chain reaction and immunostaining. RESULTS: The osteogenesis-related genes, alp, runx2, col1 and ocn expressions suggest that culture medium consisting of CM:BM at the ratio of 3:7 enhanced the osteogenic differentiation more than other concentrations that were tested. In addition, the alkaline phosphatase activity and osteogenic marker Runx2 expression demonstrate that the combination of CM and BM significantly enhanced the osteogenic differentiation of iPSC-MSCs. CONCLUSION: In summary, this study has shown that osteoblast-derived CM can dramatically enhance osteogenic differentiation of iPSC-MSCs toward osteoblasts. Results from this work will contribute to optimize the osteogenic induction conditions of iPSC-MSCs and will assist in the potential application of iPSC-MSCs for bone tissue engineering.
Alkaline Phosphatase ; Animals ; Bone and Bones ; Culture Media, Conditioned ; Induced Pluripotent Stem Cells ; Mesenchymal Stromal Cells ; Mice ; Osteoblasts ; Phenotype

Objective To investigate the correlation between late-onset sporadic parkinson's disease(PD) and single nucleotide polymorphism (SNP) of autophagy-related genes 7 (Atg7) rs2606757 (6+1196A/T)in Han Chinese population.Methods Totally 124 patients with late-onset sporadic PD(the PD group)and 105 age-and sex-matched healthy individuals(the control group)were enrolled in this study.The SNP of Atg7 rs2606757 was detected by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).After gene sequencing for the detection of allele and genotype frequencies distribution and testing Hardy-Weinberg equilibrium,the differences in Atg7 rs2606757 genotype and allele frequency were compared between PD group and control group and between males and females.Results The frequency of AA genotype was statistically significantly lower in the PD group[34.7％(43/124)]than in the control group[53.3 ％ (56/105)](x2 =8.063,P=0.005,OR =0.465,95％ CI:0.273-0.791).In men's PD group versus men's control group,AA genotype of the Atg7 rs2606757 showed a lower frequency for late-onset sporadic PD[33.3 ％ (23/69)vs.53.2 ％ (33/62),x2 =5.280,P =0.022,OR =0.439,95 ％ CI:0.217-0.891].Logistic regression analysis indicated that the AA genotype frequency distribution of Atg7 rs2606757 showed a significant difference between PD and control groups (OR =2.210,95％ CI:1.289-3.789,P =0.004).Conclusions The higher frequence of AA genotype at Atg7 rs2606757 only in males might be associated with the decreased risk of late-onset sporadic PD.

Objective To investigate the correlation between FA value,ADC value and limb muscle strength score measured by magnetic resonance imaging in patients with ischemic stroke,aims to to analyze the clinical value of magnetic resonance imaging in limb muscle strength.Methods Twenty patients with acute cerebral infarction and treated from June 2015 to Junly 2016 were recruited from This hospital,and the simplified Fugl-Meyer motor function score was observed for all patients within 3 days.Tensor imaging examination was conducted to observe the distribution of nerve fiber bundles,FA value,ADC value changes.Results The FA value and ADC value of the infarct side were significantly different from those of the contralateral side(t=8.70,t=-18.70,P＜0.05);There were significant differences in FA value and ADC value between the infarcted ventricle hind limbs and the contralateral side of the infarcted ventricle(t=-5.16,t=-5.08,P＜0.05).The FA value of the infarcted ventral hind limbs had positive correlation with the simplified Fugl-Meyer motor function score(R=0.863,P=0.013).Conclusion FA value and ADC value of acute infarct and internal hindlimb are lower than FA value and ADC value of contralateral normal white matter.The FA value of internal capsule hind limbs is closely related to the simplified Fugl-Meyer motor function score.

Objective To investigate the association between rs14016 (19 +31C/T) polymorphisms of autophagy-related genes 7 (Atg7) and Parkinson's disease (PD) in Han population in China.Methods Totally 123 patients with Parkinson's disease (PD) (case group) and 101 synchronized health controls (control group) were selected from Chinese Han population between January 2013 and July 2016.A single nucleotide polymorphism (SNP) of rs14016 of Atg7 gene was detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis.After gene sequencing for genotyping and detection of alleles,genotype and allele frequency distributions were analyzed in the two groups.Results The frequency distributions of TT genotype and T alleles were 17.9％ (22/123) and 41.1％ (101/246) in the case group,and 5.9％ (6/101) and 31.2 ％ (63/202) in the control group,respectively.The difference in genotype frequencies between the two groups was statistically significant (x2 =7.236,P =0.007,OR =3.01,95 ％ CI:1.27-7.14).The frequencies of T and C alleles were 41.1％ (101/246) and 58.9％ (145/246) respectively in the case group,and 31.2％ (63/202) and 68.8％ (139/202) in the control group (x2 =4.655,P=0.031,OR=1.32,95 ％CI:1.02-1.70),with the statistically significant difference in the allele.The TT genotype of rs14016 showed statistical significance between the two groups by logistic regression analysis (OR=3.40,95％CI:1.32-8.80,P=0.012).Conclusions The T allele and TT genotype at the rs14016 of Atg7 gene might be associated with PD,and might increase the risk for suffering from PD,which is worthy of further fully researches.

BACKGROUND:With the increasing of aging, the incidence and mortality of osteoporotic hip fracture wil rise. It is of great significance to study the pathogenesis and preventing method. At present, finite element analysis can be used to judge fracture, only for the distribution trend of fracture failure in the starting point or section view, but it cannot completely reflect actual situation of fracture. OBJECTIVE:To build the fracture model of the femoral neck fracture caused by fal ing-induced external force based on the finite element analysis LS-DYNA software, and to evaluate the effect of rupture. METHODS:CT image data of one case of elderly femoral neck fracture were col ected. Using Mimics software, region growth of the contralateral area, cavity fil ing, editing, rebuilding the contralateral proximal femur model were conducted. Data were imported in Hypermesh and LS-DYNA software for meshing, and defining material properties. The failure parameters and interfacial properties were set. The load and force boundary constraints simulating the fal ing were simulated. The model of femoral neck fracture was calculated. Rupture effect was evaluated. RESULTS AND CONCLUSION:(1) The validity of contralateral proximal femur three-dimensional model was verified. Based on the finite element analysis software LS-DYNA, the femoral neck fracture model matched the actual fracture line to a degree of close to 83%. (2) Above results confirmed that based on the finite element analysis, LS-DYNA software can wel simulate the femoral neck fracture, which provides experimental basis to the exploration of femoral neck fracture classification mechanism caused by different fal ing-induced external forces.

Objective To assess the correlation between the pregnancy‐associated plasma protein A (PAPP‐A)level with gesta‐tional diabetes mellitus(GDM )in primiparous women .Methods The nonparametric test and Logistic regression analysis were used to retrospectively analyze 168 pregnant women of GDM and 273 normal pregnant women ,including age ,body weight ,PAPP‐A ,freeβ‐human chorionic gonadotropin(fβ‐hCG) .Results The age had significant difference between GDM group and control group(P<0 .01) ,the PAPP‐A concentration and corrected multiple of the median (MoM )of PAPP‐A in the GDM group were significantly lower than those in the control group(P<0 .01) .Conclusion Low level of PAPP‐A during early pregnant stage in primiparas is strongly associated with GDM and can be used as the risk factor of GDM .