Objective:To explore the evaluation effect of ultrasonography and Pirani score on tarsal deformity, treatment effect and pseudo-correction of congenital clubfoot in infants and young children, and the correlation between the two methods.Methods:This is a retrospective case series study. The clinical data of 26 children (40 feet) with congenital clubfoot who were evaluated by ultrasonography in the Third Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected. There were 16 males and 10 females. The age at the first ultrasound examination was ( M(IQR)) 9.0 (18.0) days (range: 1 to 46 days). All patients were treated with Ponseti method by the same physician. The Pirani scores before and after treatment and at the last examination, and the talonavicular angle, calcaneocuboid angle and tibiocalcaneal angle measured by ultrasound were collected, and the treatment and follow-up were recorded. Paired sample t test, repeated measures analysis of variance or Kruskal-Wallis test were used for data comparison, and Spearman correlation analysis was used for correlation analysis. The receiver operating characteristic curve was used to calculate the efficacy of ultrasound in evaluating different Pirani scores. Results:The number of plaster fixation in 26 children was 4.0 (1.0) times (range: 2 to 8 times). The medial talonavicular angle and posterior tibiocalcaneal angle were significantly improved after treatment and at the last follow-up compared with those before treatment, and the differences were statistically significant (all P<0.01). There was no difference in lateral calcaneocuboid angle before and after treatment and at the last follow-up ( F=1.971, P>0.05). Pseudo-correction occurred in 2 cases (2 feet) during the treatment, with an incidence of 5%. Correlation analysis showed that there was a moderate positive correlation between talonavicular angle and Pirani midfoot score ( r=0.480, P<0.01). There was no correlation between calcaneocuboid angle and Pirani midfoot score ( r=0.114, P=0.105). There was a moderate negative correlation between tibial heel angle and Pirani hindfoot score ( r=-0.566, P<0.01). The cut-off point of Pirani midfoot score of 1.5 was 38.78°, the sensitivity was 0.90, the specificity was 0.56, and the area under the curve was 0.75. The cut-off value of angle was 27.51 °, the sensitivity was 0.16, the specificity was 0.92, and the area under the curve was 0.44.The cut-off points of Pirani midfoot score of 3.0 were 45.08°and 9.96°, the sensitivity was 0.94 and 0.91, the specificity was 0.37 and 0.42, and the area under the curve was 0.59 and 0.62, respectively. The cut-off values of Pirani hindfoot score of 2.0 and 3.0 were 167.46° and 160.15°, respectively. The sensitivity was 0.75 and 0.67, the specificity was 0.81 and 0.83, and the area under the curve was 0.78 and 0.71, respectively. Conclusion:Ultrasound can complement with Pirani score, visually and dynamically observe the morphology and position changes of talonavicular joint, calcaneocuboid joint and tibiotalocalcaneal joint, monitor the recovery and pseudo-correction of tarsal bones, and better evaluate the therapeutic effect.

Objective:To explore the evaluation effect of ultrasonography and Pirani score on tarsal deformity, treatment effect and pseudo-correction of congenital clubfoot in infants and young children, and the correlation between the two methods.Methods:This is a retrospective case series study. The clinical data of 26 children (40 feet) with congenital clubfoot who were evaluated by ultrasonography in the Third Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected. There were 16 males and 10 females. The age at the first ultrasound examination was ( M(IQR)) 9.0 (18.0) days (range: 1 to 46 days). All patients were treated with Ponseti method by the same physician. The Pirani scores before and after treatment and at the last examination, and the talonavicular angle, calcaneocuboid angle and tibiocalcaneal angle measured by ultrasound were collected, and the treatment and follow-up were recorded. Paired sample t test, repeated measures analysis of variance or Kruskal-Wallis test were used for data comparison, and Spearman correlation analysis was used for correlation analysis. The receiver operating characteristic curve was used to calculate the efficacy of ultrasound in evaluating different Pirani scores. Results:The number of plaster fixation in 26 children was 4.0 (1.0) times (range: 2 to 8 times). The medial talonavicular angle and posterior tibiocalcaneal angle were significantly improved after treatment and at the last follow-up compared with those before treatment, and the differences were statistically significant (all P<0.01). There was no difference in lateral calcaneocuboid angle before and after treatment and at the last follow-up ( F=1.971, P>0.05). Pseudo-correction occurred in 2 cases (2 feet) during the treatment, with an incidence of 5%. Correlation analysis showed that there was a moderate positive correlation between talonavicular angle and Pirani midfoot score ( r=0.480, P<0.01). There was no correlation between calcaneocuboid angle and Pirani midfoot score ( r=0.114, P=0.105). There was a moderate negative correlation between tibial heel angle and Pirani hindfoot score ( r=-0.566, P<0.01). The cut-off point of Pirani midfoot score of 1.5 was 38.78°, the sensitivity was 0.90, the specificity was 0.56, and the area under the curve was 0.75. The cut-off value of angle was 27.51 °, the sensitivity was 0.16, the specificity was 0.92, and the area under the curve was 0.44.The cut-off points of Pirani midfoot score of 3.0 were 45.08°and 9.96°, the sensitivity was 0.94 and 0.91, the specificity was 0.37 and 0.42, and the area under the curve was 0.59 and 0.62, respectively. The cut-off values of Pirani hindfoot score of 2.0 and 3.0 were 167.46° and 160.15°, respectively. The sensitivity was 0.75 and 0.67, the specificity was 0.81 and 0.83, and the area under the curve was 0.78 and 0.71, respectively. Conclusion:Ultrasound can complement with Pirani score, visually and dynamically observe the morphology and position changes of talonavicular joint, calcaneocuboid joint and tibiotalocalcaneal joint, monitor the recovery and pseudo-correction of tarsal bones, and better evaluate the therapeutic effect.

Objective:To investigate the expression and clinical significance of decoy receptor 3 (DcR3) and its signal pathway-related molecules in PBMCs of patients with ankylosing spondylitis (AS).Methods:Peripheral blood samples, clinical data and laboratory test results were collected from 100 patients with ankylosing spondylitis [50 patients with AS activity (ASA), 50 patients with AS stability (ASS)], 30 patients with osteoarthritis and 30 patients with gouty arthritis (as disease control group), and 60 healthy controls (HC). The mRNA expression levels of DcR3 and its signal pathway related genes (DR3, TL1A, Fas, FasL, LIGHT, LIGHTR, LTβR) were measured by real-time fluorescence quantitative polymerase chain reaction. Measurement data among the three groups in normal distribution were analyzed by t test or one-way analysis of variance, pairwise comparisons using LSD- t test, non-normal distribution data were analyzed by Mann-Whitney test or Kruskal-Wallis H test, χ2 test was used for correlation analysis of categorical variables. Correlation analysis between variables were analyzed using Spearman correlation analysis. Results:① By comparing the AS group, disease control group and HC group, the expression levels of DcR3 mRNA and DR3 mRNA in the AS group were lower than those in disease control group and HC group, and DcR3 mRNA and DR3 mRNA in disease control group were lower than those in the HC group {DcR3mRNA: [6.21 (3.89, 10.70)]×10 -4vs [9.51 (5.89, 16.65)]×10 -4vs [17.81 (11.27, 24.20)]×10 -4, H=55.28, P<0.001; DR3 mRNA: [41.05 (24.09, 66.95)]×10 -4vs [58.28 (28.41, 94.38)]×10 -4vs [94.79 (54.07, 144.51)]×10 -4, H=37.10, P<0.001}. The expression level of TL1A mRNA in the AS group was higher than that in disease control group {[14.71(4.91, 42.22)]×10 -4vs [4.00(1.07, 16.60)]×10 -4vs [7.70 (3.52, 27.83)]×10 -4, H=17.71, P<0.001}; The expression level of Fas mRNA in AS group and disease control group was lower than that in HC group {[20.99(4.63, 62.89)]×10 -4vs [23.97(15.82, 38.99)]×10 -4vs [78.45 (27.32, 146.46)]×10 -4, H=31.17, P<0.001}. The expression level of FasL mRNA in AS group was higher than that in disease control group and HC group {[42.87(6.57, 91.21)]×10 -4vs [5.45(2.83, 10.32)]×10 -4vs [6.88 (4.57, 23.79)]×10 -4, H=46.42, P<0.001}. The expression level of LIGHTR mRNA in AS group was lower than that in disease control group {[52.66 (7.20, 143.21)]×10 -4vs [98.80 (53.11, 166.24)]×10 -4vs [63.47(40.85, 138.07)]×10 -4, H=11.96, P<0.001}. There were no significant differences in LIGHT mRNA and LTβR mRNA among all groups ( H=0.86, P>0.05; H=3.18, P>0.05). ②The expression levels of DcR3 mRNA, DR3 mRNA and Fas mRNA in ASA group and ASS group were lower than those in HC group. DcR3 mRNA in ASA group was higher than that in ASS group, and DR3 mRNA in ASA group was lower than that in ASS group {DcR3 mRNA: [7.28 (4.92, 16.56)]×10 -4vs [4.59 (2.49, 7.03)]×10 -4vs [17.81 (11.27, 24.20)]×10 -4, H=62.63, P<0.001; DR3 mRNA: [30.93(16.18, 66.66)]×10 -4vs [47.17(29.91, 67.40)]×10 -4vs [94.79(54.07, 144.51)]×10 -4, H=41.48, P<0.001; Fas mRNA: [20.04(3.29, 62.30)]×10 -4vs [22.49(5.63, 64.79)]×10 -4vs [78.45(27.32, 146.46)]×10 -4, H=23.54, P<0.001}. The expression levels of TL1A mRNA and LTβR mRNA in the ASA group were higher than those in the ASS group and the HC group {TL1A mRNA: [32.36(10.09, 97.84)]×10 -4vs [9.98(1.29, 21.63)]×10 -4vs [7.70(3.52,27.83)]×10 -4, H=21.14, P<0.001; LTβR mRNA: [6.13(2.16,20.06)×10 -4vs [2.13(0.53,8.04)]×10 -4vs [2.72 (1.24,5.73)]×10 -4, H=12.86, P<0.001}. The expression level of FasL mRNA in the ASA group and the ASS group was higher than that in the HC group {[60.70 (8.16, 106.16)]×10 -4vs [30.14 (5.37, 78.40)]×10 -4vs [6.88 (4.57, 23.79)]×10 -4, H=18.99, P<0.001}. The expression level of LIGHTR mRNA in ASS group was lower than that in HC group {[49.79(10.75, 168.48)]×10 -4vs [15.92(3.27, 105.91)]×10 -4vs [63.47(40.85, 138.07)]×10 -4, H=11.80, P<0.001]. There was no significant difference in LIGHT mRNA among all groups ( H=4.15, P>0.05). ③Spearman correlation analysis showed that DcR3 level was positively correlated with BASDAI score and hsCRP in AS patients ( r=0.52, P<0.001; r=0.35, P<0.01), and DR3 level was negatively correlated with BASDAI score, ESR and hsCRP level ( r=-0.28, P<0.001; r=-0.25, P<0.001; r=-0.31, P<0.001). TL1A was positively correlated with BASDAI score, ESR and hsCRP level ( r=0.23, P=0.046; r=0.26, P=0.015; r=0.25, P=0.017). Conclusion:DcR3 and its signal pathway-related molecules are differentially expressed in PBMCs of patients with AS, suggesting that they may participate in the occurrence and development of AS.

Both cholinergic dysfunction and protein citrullination are the hallmarks of rheumatoid arthritis (RA), but the relationship between the two phenomena remains unclear. We explored whether and how cholinergic dysfunction accelerates protein citrullination and consequently drives the development of RA. Cholinergic function and protein citrullination levels in patients with RA and collagen-induced arthritis (CIA) mice were collected. In both neuron-macrophage coculture system and CIA mice, the effect of cholinergic dysfunction on protein citrullination and expression of peptidylarginine deiminases (PADs) was assessed by immunofluorescence. The key transcription factors for PAD4 expression were predicted and validated. Cholinergic dysfunction in the patients with RA and CIA mice negatively correlated with the degree of protein citrullination in synovial tissues. The cholinergic or alpha7 nicotinic acetylcholine receptor (α7nAChR) deactivation and activation resulted in the promotion and reduction of protein citrullination in vitro and in vivo, respectively. Especially, the activation deficiency of α7nAChR induced the earlier onset and aggravation of CIA. Furthermore, deactivation of α7nAChR increased the expression of PAD4 and specificity protein-3 (SP3) in vitro and in vivo. Our results suggest that cholinergic dysfunction-induced deficient α7nAChR activation, which induces the expression of SP3 and its downstream molecule PAD4, accelerating protein citrullination and the development of RA.

Objective:To compare the perioperative outcomes between robotic pancreaticoduodenectomy(RPD)and laparoscopic pancreaticoduode-nectomy(LPD)in patients aged ≥65 years. Methods:The clinical data of 130 patients aged ≥65 years who received minimally invasive pancreaticoduodenectomy(MIPD)at Department of Gastrointestinal and Pancreatic Surgery,Zhejiang Provincial People's Hospital from January 2019 to December 2022 were retrospectively analyzed.The patients were divided into the RPD group(n=66)and the LPD group(n=64)according to the operation method,and the perioperative clinical data were compared between the 2 groups. Results:Compared with the LPD group,the average age of patients in the RPD group was higher than that of the LPD group[(71.95±4.73)years vs(70.39±3.9)years,P＜0.05];the RPD group had more patients with diabetes(39.4％vs 18.8％,P＜0.05)and cardiopulmonary diseases(37.9％vs 17.2％,P＜0.05);the RPD group had shorter operation time[(272.91± 68.38)min vs(362.81±78.24)min,P＜0.05]and less intraoperative blood loss[median(range):1 00 mL(50-200 mL)vs 1 50 mL(1 00-200 mL),P＜0.05)];the RPD group had higher incidence of chylous fistula(1 2.1％vs 1.6％,P＜0.05)but lower incidence of surgical morbidity(37.9％vs 46.9％),serious complications(19.7％vs 34.4％),postoperative pancreatic fistula(12.1％vs 17.2％),biliary fistula(3.0％vs 3.1％),abdominal infection(10.6％vs 14.1％),postoperative bleeding(4.5％vs 4.5％),and postoperative cardiopulmonary complications(1 2.1％vs 20.3％)with no statistically significant difference(P＞0.05);the RPD group waited shorter time before restarting diet[(3.97±1.59)d vs(5.34±2.56)d,P＜0.05]. Conclusion:MIPD is safe and feasible in patients aged ≥65 years.The incidence of perioperative complications is similar between the 2 groups.Compared with LPD,RPD has shorter operation time,less intraoperative blood loss,and shorter duration before restarting diet after operation,which has certain clinical advantages.

Objective:To This study was to investigate the expression and possible clinical significance of microRNA-146b (miR-146b) and signal transducer and transcriptional activator 1 and 3 (STAT1/3) in peripheral blood mononuclear cells (PBMCs) of patients with primary gouty arthritis (GA).Methods:The peripheral blood samples, clinical data and laboratory indexes of 120 male cases of GA [including 57 cases of acute (AG group) and 63 cases of intermittent (IG group)]and 66 healthy subjects (HC group) were collected. The expression levels of miR-146b and STAT1/3 in PBMCs were detected by real-time fluorescence quantitative PCR (RT-qPCR). The differences among the three groups were compared and the correlation between them and clinical indexes was analyzed. The receiver operating characteristic curve (ROC) was constructed to evaluate its diagnostic value in GA. After the PBMCs of 18 healthy subjects were stimulated by 100 μg/ml MSU for 3 hours to simulate acute gout inflammatory environment, the transcriptional changes of IL-1β, miR-146b and STAT1/3 were detected by RT-qPCR, and the expressions of IL-1β, STAT1/3 protein and phosphorylated protein were detected by Western blotting. T test or one-way ANOVA and LSD- t test were used in accordance with the normal measurement data, Kruskal-Wallis H and Mann-Whitney U test were used in the non-normal data, Spearman correlation analysis was used in the correlation between variables, and the diagnostic value was evaluated by the receiver working characteristic curve ROC. Results:①There were statistical differences in the expression of miR-146b, STAT1 and STAT3 among the three groups ( F=7.02、19.52、17.07, all P<0.001). The expression of miR-146b in gout group [(0.32±0.28)] was significantly higher than that in HC group (0.19±0.18)( t=2.96, P=0.003), while STAT1(0.019±0.012) and STAT3(0.014±0.010) were significantly lower than those in HC group (0.038±0.029),(0.025±0.016)( t=6.26, 5.56, both P<0.001). Further subgroup analysis showed that the expression of miR-146b in AG and IG groups was higher than that in HC group[(0.27±0.17), (0.38±0.35), (0.19±0.18), t=2.09, 3.30, both P<0.05], but that in AG group was lower than that in IG group ( t=2.02, P<0.05). The expression of STAT1 mRNA in AG and IG groups was lower than that in HC group [(0.020±0.012), (0.019±0.012), (0.038±0.029), t=4.89, 4.56, both P<0.001], but there was no statistical significance between AG and IG groups ( t=0.24, P>0.05). The expression of STAT3 mRNA in AG and IG groups was lower than that in HC group [(0.016±0.012), (0.012±0.008), (0.025±0.016), t=5.64, 3.33, both P<0.01], and the expression of STAT3 mRNA in AG group was higher than that in IG group ( t=2.12, P<0.05). ② Spearman correlation analysis showed that the expression of miR-146b in GA was negatively correlated with HCY ( r=-0.37, P=0.014), STAT1 was negatively correlated with Crea ( r=-0.29, P=0.019), positively correlated with eGFR ( r=0.25, P=0.047), and STAT3 was negatively correlated with HDL-C ( r=-0.27, P=0.033). ③ROC curve showed that the AUC (95% CI) of miR-146b, STAT1 and STAT3 were 0.679(0.582, 0.776), 0.710(0.629, 0.791) and 0.705(0.626, 0.783), and the combined AUC(95% CI) of the three was 0.836 (0.765, 0.907). ④Compared with blank control group and negative control group, the expression of miR-146b in PBMCs of 18 cases of HC was significantly decreased ( H=14.44, P=0.003), while the expression of IL-1β, STAT1 and STAT3 mRNA was significantly increased after 3 h of MSU stimulation ( H=26.44、27.26、15.90, all P<0.001). The expression of IL-1β, STAT1 and STAT3 protein and phosphorylated protein in the model group were significantly higher than those in the blank control group, and the differences were statistically significant ( t=9.97、6.63、7.48、11.25、6.28, all P<0.01). Conclusion:The abnormal expression of miR-146b and STAT1/3 in GA is related to some clinical indicators, suggesting that it may be involved in the regulation of gout immune inflammatory response and metabolism, and the specific mechanism is worth further study.

【Objective】 To provide reference for fine management of blood donors by classifying and analyzing different types of blood donors from domestic blood stations. 【Methods】 The resident population of 15 regions in China from 2016 to 2019 were taken as the research object, among which the blood donors were divided into three categories: age-eligible citizens, registered donors and donated donors. The average value and proportion of the three categories were calculated and statistically analyzed. 【Results】 The resident population of the 15 regions varied greatly. The mean 95% CI of the proportion of age-eligible citizens to resident population from 2016 to 2019 was (60.16%, 67.84%); registered donors to age-eligible citizens and resident population was (2.21%, 2.86%) and (1.41%, 1.79%), respectively; donated donors to registered donors, age-eligible citizens and resident population was (84.63%, 91.68%), (1.93%, 2.55%) and(1.23%, 1.59%), respectively. 【Conclusion】 There were differences in the number and proportion of different types of blood donors in different regions. The fine management of blood donors can help blood stations carry out more effective recruitment and retention strategies.

Objective:To produce 161Tb from enriched 160Gd 2O 3 isotope-enriched target material and realize domestic production of the novel medical isotope 161Tb. Methods:The 160Gd 2O 3 isotope-enriched target material was irradiated with neutrons by the China Mianyang Research Reactor (CMRR). The no-carrier-added 161Tb product was obtained after the processes of target broken, sample dissolution, separation and purification with lanthanide (LN) resin and solution replacement with diglycolamide (DGA) column. Various key indicators such as γ spectral purity, metal impurity content, specific activity, radiochemical purity, and radioactive concentration were used to conduct the quality inspection and the control of 161Tb products. Results:161TbCl 3 of 33.4 GBq was obtained in a single time with the radioactive concentration of 16.8 GBq/ml, nuclear purity more than 99.9%, and radiochemical purity of 99.2%. Metal impurity content was met the established standards, with the specific activity of 6.02×10 17 Bq/mol. The radiochemical purities of 161Tb labeling with 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) after 0 and 72 h were 100% and 95.8% respectively. Conclusion:The preparation of no-carrier-added 161Tb by using LN resin has the advantages of high separation performance and high sample loading, which has great significance in the field of medical isotope preparation and lays a good nuclide guarantee for the research and development of domestic 161Tb-labeled drugs.

Objective:To evaluate the association between periodontitis and mild cognitive impairment (MCI), and explore the potential local oral risk factors for MCI.Methods:The study included 70 middle-aged and elderly subjects (44 females and 26 males) with periodontal disease who were first diagnosed by the Department of Periodontology or referred by the Department of Geriatrics in Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from January 2021 to January 2022. In this study, the control group consisted of periodontal disease patients without cognitive impairment, and the case group (MCI group) consisted of those diagnosed with MCI referred by the geriatrics specialists. Full-mouth periodontal examinations of all subjects were performed and periodontal indicators were recorded by periodontists, while digital panoramic radiographs were taken. The severity of periodontitis was defined according to the 1999 classification, and the staging and grading of periodontitis were defined according to the 2018 American Academy of Periodontology and European Federation of Periodontology classification. The mini-mental state examination scale was chosen by geriatricians to evaluate the cognitive function of the included subjects. The cubital venous blood was drawn to detect the expression levels of inflammatory factors such as hypersensitive C-reactive protein (hs-CRP), interleukin (IL)-1β, IL-6 and tumor necrosis factor-α(TNF-α) in serum. Independent-samples t test and chi-square test were used to analyze the differences in population factors, periodontal-related indexes and serum inflammatory factors between the two groups (α=0.05). Odds ratios ( OR) for MCI according to the severity of periodontitis and main periodontal clinical indexes were calculated by binary Logistic analysis. Results:Thirty-nine subjects were included in the control group and thirty-one in the MCI group. The age of the study population was (58.3±6.2) years (range: 45-70 years). The comparison between two groups showed that the control group was with higher educational background (χ2=9.45, P=0.024) and 2.6 years younger than the MCI group [(57.1±6.0) years vs. (59.7±6.3) years, t=-1.24, P=0.082]. The number and proportion of moderate to severe periodontitis in control group were significantly lower compared to those in MCI group (17 cases with 43.6% vs. 23 cases with 74.2%, χ2=6.61, P=0.010), and the OR of moderate to severe periodontitis adjusted by age and educational background was 3.00 (95 %CI: 1.01-8.86, P=0.048). Compared with the grading (χ2=5.56, P=0.062) of periodontitis, staging had a greater impact on MCI (χ2=7.69, P=0.041), moreover the proportion of MCI in stage Ⅰ grade A periodontitis was significantly lower than any other type of periodontitis (χ2=13.86, P=0.036). In addition, less presence of deep periodontal pockets [probing depth (PD)≥6 mm] (17.9% vs. 41.9%, χ2=4.87, P=0.027), fewer number of PD≥4 mm (6.48±6.70 vs. 11.03±8.91, t=-2.44, P=0.017), lower plaque index (1.42±0.56 vs. 1.68±0.57, t=-1.91, P=0.059) and gingival index (1.68±0.29 vs. 1.96±0.30, t=-3.93, P<0.001) were in the control group than in the MCI group. However, there were no significant differences between the two groups in the levels of serum inflammatory factors, such as hs-CRP, IL-1β, IL-6 and TNF-α ( P>0.05). Conclusions:It appears a strong correlation between moderate to severe periodontitis and the incidence of MCI in middle-aged and elderly people. Moreover, deep and increased number of periodontal pockets, poor oral hygiene, and severe gingival inflammation can be potentially associated risk factors for MCI.

Mineralized tissue regeneration is an important and challenging part of the field of tissue engineering and regeneration. At present, autograft harvest procedures may cause secondary trauma to patients, while bone scaffold materials lack osteogenic activity, resulting in a limited application. Loaded with osteogenic induction growth factor can improve the osteoinductive performance of bone graft, but the explosive release of growth factor may also cause side effects. In this study, we innovatively used platelet-rich fibrin (PRF)-modified bone scaffolds (Bio-Oss
Autografts ; Bone Regeneration ; Cell Differentiation ; Humans ; Mesenchymal Stem Cells ; Osteogenesis ; Tissue Engineering ; Tissue Scaffolds