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Objective:To summarize long-term outcome of sacral neuromodulation (SNM) for refractory interstitial cystitis/bladder pain syndrome (IC/BPS).Methods:Between January 2013 and October 2020, 28 patients with IC / BPS who received SNM in Beijing Chaoyang Hospital and Hebei Yanda Hospital were retrospectively analyzed. There were 5 males and 23 females, with median age 63.00 (47.50, 66.75) years old. The urgency score was 4 (3, 4) points, 24-hour micturition frequency was 26 (20.50, 32.50) times, nocturia was 9 (7, 12) times, single urine volume was 59.00 (41.25, 79.50) ml, VAS score was 9.0 (8.0, 9.0) points, O′Leary-Sant score was 31.00 (20.25, 33.00) points, and single maximum urine volume was 100.0 (80.0, 127.5) ml. The improvement of symptoms before operation, test period and last follow-up were compared.Results:The urgency score was 2 (1, 3), the 24-hour micturition frequency was 17.00 (15.00, 22.75), the frequency of nocturia was 5.5 (4.0, 7.0), the single urine volume was 87.50 (70.25, 110.00) ml, the VAS score was 4.0 (3.0, 6.0) and the O′Leary-Sant score was 20.00 (17.00, 23.00) in 28 patients during the test period, which were significantly improved compared with those before operation ( P < 0.05). There was no significant difference in the single maximum urine volume of 135.0 (102.5, 160.0) ml between the two groups ( P > 0.05). 28 patients received SNM Ⅱ permanent stimulator implantation. The median follow-up time was 29.5 (21.25, 61.75) months. Among the 28 patients, 3 patients underwent cystectomy and ileal conduit after removal of the complete SNM system due to the unsatisfied results. Twenty-five cases (89.3%) were still treated with SNM. Among them, 6 cases accepted combinative therapy of oral medicine (antihistamines, sodium pentose polysulfate, hormones, immunosuppressants, etc.). Two cases accepted combinative therapy of intravesical instillation, including heparin in one case and sodium hyaluronate in the other one. Three cases accepted combinative therapy of botulinum toxin injection.One case accepted combinative therapy of bladder augmentation. Two cases accepted combinative therapy of traditional Chinese medicine (TCM). One case accepted combinative therapy of oral medicine and TCM. The remaining 10 cases didn't accept any treatment. Among them, 3 cases were still treated with SNM even though they were not satisfied with the effect, including 1 case due to electrode displacement. At the last follow-up of 25 patients, the urgency score was 2 (1, 3), the 24-hour micturition frequency was 16.50 (13.00, 19.75), the frequency of nocturia was 5.5 (4.0, 9.0), the single urine volume was 105.0 (72.5, 120.0) ml, the VAS score was 4.5 (3.0, 6.0) and the O'Leary Sant score was 16.00 (14.00, 22.50), which were significantly improved compared with those before operation ( P < 0.05), but no difference with those during test period ( P>0.05). There was no significant difference in the single maximum urine volume of 125.0 (102.5, 150.0) ml at the last follow-up compared with preoperative and test period ( P>0.05). Conclusions:As a treatment option for refractory IC / BPS, SNM can improve the symptoms of most patients and maintain good long-term efficacy combined with other.
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Objective:We compare the consistency, similarities and differences of operating procedures, data and conclusions of air-charged catheters(ACC) and water-filled catheters(WFC), as simultaneously using ACC and WFC in pressure-flow study(PFS).Methods:This study was a prospective, synchronously controlled study, including eligible patients who underwent PFS in the Department of Urology, Beijing Chaoyang Hospital from January 2021 to March 2021. Inclusion criteria: ① Patients need PFS for lower urinary tract symptoms like frequency of urination, urgent urination, urinary incontinence and dysuria; ② Age over 18 years old. Exclusion criteria: ① Unable to complete or cooperate during the urodynamic test; ② Patients with severe urethral stricture or acute stage urinary tract infection; ③ Pregnant women. The bladder pressure was measured continuously by using a 7FDR T-DOC ?AC three-chamber bladder pressure tube, which linked to ACC sensor and improved WFC pressure conduction module. At the same time, 7FA T-DOC ?AC single-lumen rectal pressure tube and 7F Labori-CAT411 double-lumen water sac abdominal pressure tube was used to measure the ACC and WFC rectum pressure, respectively. We recorded the Pdet, Pves and Pabd measured by ACC and WFC, at the point of initial sitting position, bladder filling at 100 ml, 150 ml, 200 ml, cough, Q max, maximum Pdet and the end of urination, and compared the mean values, differences, and consistencies of our data. Result:A total of 63 patients (26 female, 37 male) were included in this study, with an average age of 59.19 years (25-86 years old). During bladder filling phase, the mean values of Pves measured by ACC and WFC were 30.78/24.67cmH 2O (initial sitting position), 29.79/25.13cmH 2O (100 ml), 30.87/25.90cmH 2O (150 ml) and 30.95/26.17cmH 2O(200 ml), respectively, the mean value of Pabd were 30.03/24.17cmH 2O (initial sitting position), 28.81/21.78cmH 2O (100ml), 28.89/21.38cmH 2O (150ml), 28.44/21.60cmH 2O (200ml), respectively, and were significantly different at each sampling point ( P<0.01). During urination period, no significant differences were found in data( P>0.05), and the data measured with ACC and WFC system have good consistency. There were significant differences in Pves(mean 57.30/49.95 cmH 2O, respectively) and Pdet(mean 54.21/43.10 cmH 2O, respectively) between ACC and WFC in cough ( P<0.01), but there was a strong linear correlation between these data between two systems(R 2=0.792 in Pves and 0.756 in Pabd). Bland-Altman analysis showed that detrusor pressure at the maximum urine flow rate maintained good consistency between ACC and WFC, which 95% CI was -13.9 cmH 2O to 15.8 cmH 2O. Conclusions:In PFS, although the ACC measurement values (Pves and Pabd) during the filling phase are higher than those WFC readings, but the absolute measurement difference is small, so there is no practical meaning in clinical practice. There was no significant difference in detrusor pressure measured during voiding phase, which indicated that the urodynamic judgment and clinical conclusions of the two systems are highly consistent in judgment of the detrusor contractility and the bladder outlet obstruction.
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Objective:To investigate the effect of GluA2-3Y which is an inhibitor of AMPA(α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptor internalization on cognitive function and hippocampal postsynaptic protein expression in rats with chronic cerebral hypoperfusion.Methods:Forty-eight adult male SD rats were randomly divided into Sham group, 2VO group, high-dose GluA2-3Y group and low-dose GluA2-3Y group according to random number table, with 12 rats in each group.The chronic cerebral hypoperfusion model of rat was established by two vessel occlusion (2VO) while the Sham operation was performed in rats of Sham group.The rats in high dose GluA2-3Y group and low dose GluA2-3Y group were intraperitoneal injected with 3 μmol/kg and 0.03 μmol/kg GluA2-3Y respectively once a day for 2 weeks. Rats in 2VO group and Sham group were intraperitoneally injected with control peptide. Morris water maze test and new object recognition test were performed to evaluate the learning and memory ability of rats, and Western blot was used to evaluate the expression of Akt1、GSK3β、p-GSK3β、GluA2 and PSD-95 in rat hippocampus. The expressions of GluA2 and PSD-95 in rat hippocampus were evaluated by immunofluorescence. SPSS 23.0 software was used for data analysis. The comparison between multiple groups was analyzed by one-way ANOVA and repeated measurement ANOVA was used to analyze Morris water maze results. And independent-samples t-test was used for pairwise comparisons. Results:(1)In Morris water maze trials, the results of repeated measurement ANOVA showed that the interaction between group and time of escape latency of rats in each group was not significant ( F=0.79, P>0.05), and the group main effect and time main effect were significant ( F=24.44, 40.42, both P<0.05). On the 5th day of navigation trials, the escape latency of rats in 2VO group was longer than that in sham group ( t=5.87, P<0.05). The escape latency of rats in low dose GluA2-3Y group and high dose GluA2-3Y group were significantly shorter than that in 2VO group ( t=2.20, 3.41, both P<0.05), but there was no significant difference between low dose GluA2-3Y group and high dose GluA2-3Y group ( t=1.37, P>0.05). The target quadrant residence time and resolution coefficient ((14.57±1.40)s, (0.15±0.10)) in 2VO group were significantly lower than those in Sham group ((23.71±2.57)s, (0.40±0.06)) ( t=3.23, 2.24, both P<0.05), while the target quadrant residence time in high dose GluA2-3Y group ((20.19±1.53)s) and low dose GluA2-3Y group ((20.31±2.06)s) were longer than that in 2VO group( t=2.71, 2.35, both P<0.05). The discrimination coefficients in high dose GluA2-3Y group (0.47±0.10) and low dose GluA2-3Y group (0.59±0.06) were higher than that of 2VO group ( t=2.21, 3.94, both P<0.05). (2)The Western blot results showed that the expression of PSD-95 and GluA2 in hippocampus of rats in 2VO group were significantly lower than those in Sham group ( t=2.31, 2.20, both P<0.05), and the expression of PSD-95 in high dose GluA2-3Y group (1.026±0.056) was significantly higher than that in 2VO group ((0.760±0.061), t=2.49, P<0.05), while there was no significant difference between low-dose GluA2-3Y group and 2VO group( t=0.96, P>0.05). The expression of GluA2 in low-dose GluA2-3Y group was higher than that in 2VO Group ((1.130±0.087), (0.766±0.080), t=2.37, P<0.05), but there was no significant difference between high-dose GluA2-3Y group and 2VO group( t=1.06, P>0.05). (3) Immunofluorescence showed that compared with Sham group, the expression of PSD-95 and GluA2 in 2VO group decreased ( t=4.23, 2.57, P<0.05). Compared with 2VO group, the expression of PSD-95 and GluA2 in high dose GluA2-3Y group and low dose GluA2-3Y group increased significantly, and the differences were statistically significant (PSD-95: (7.757±0.578), (12.057±0.578), t=3.14, 6.96, both P<0.05; (9.721±0.950), (16.610±0.950), t=4.56, 9.34, both P<0.05). (4) The results of Western blot showed that the expression GSK3β in hippocampus of rats in each group were not statistically different( F=2.03, P>0.05). There were significant differences in the expression of Akt1, p-GSK3β and the percentage of p-GSK3β/GSK3β in hippocampus of rats in each group ( F=8.30, 4.76, 3.57, all P<0.05). Compared with Sham group, the levels of Akt1, p-GSK3β and the percentage of p-GSK3β/GSK3β in 2VO group were significantly lower ( t=3.00, 2.81, 3.17, all P<0.05). Compared with 2VO group, the levels of Akt1, p-GSK3β and p-GSK3β/GSK3β percentage in low dose GluA2-3Y group and high-dose GluA2-3Y group were significantly higher (Akt1: t=2.05, 5.20, both P<0.05; p-GSK3β: t=2.49, 4.15, both P<0.05; p-GSK3β/GSK3β percentage: t=2.30, 2.97, both P<0.05). Conclusion:GluA2-3Y, an AMPA receptor internalization inhibitor, can alleviate the cognitive impairment in rats with chronic cerebral hypoperfusion, which may be related to the increased expression of Akt1, p-GSK3β and postsynaptic proteins.
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ObjectiveTo investigate the clinical significance of highly sensitive nucleic acid detection in precise antiviral therapy for patients with liver cirrhosis and its association with aminotransferase level. MethodsA total of 377 patients with hepatitis B cirrhosis who were hospitalized or attended the outpatient service from May 2013 to April 2019 were enrolled and tested by both domestic HBV DNA detection and highly sensitive Cobas HBV DNA detection. All patients underwent biochemical examination, four blood coagulation tests, routine blood test, and upper abdominal computed tomography or ultrasound. Sensitivity of different HBV DNA detection reagents was compared in liver cirrhosis patients with a low viral load, and the correlation between alanine aminotransferase (ALT) level and viral load was analyzed. The paired t-test was used for comparison of continuous data before and after treatment. The receiver operating characteristic (ROC) curve was used to screen out the optimal predictive values of ALT at different cut-off values of HBV DNA. ResultsAmong the 377 patients with hepatitis B cirrhosis, 215 tested positive and 162 tested negative by domestic HBV DNA, and among these 162 patients, 104 (64.2%) tested positive by Cobas HBV DNA detection, with a mean level of 267.5±42.3 IU/ml. After 24 weeks of antiviral therapy, the 104 patients with hepatitis B cirrhosis had significant improvements in viral replication level, ALT, and Child-Pugh score for liver function; HBV DNA decreased from 267.5±32.2 IU/ml before treatment to 59.6±7.7 IU/ml after treatment (t=3.486, P=0.002), ALT decreased from 871±10.8 U/L before treatment to 36.5±7.6 U/L after treatment (t=3.235, P=0.020), and the Child-Pugh score decreased from 6.5±0.7 before treatment to 5.7±0.5 after treatment (t=2.928, P=0.041). The ROC curve analysis of ALT in predicting HBV DNA decision point showed that an ALT level of 29 IU/L was the most sensitive cut-off value for predicting HBV DNA ＜20 IU/ml, with an area under the ROC curve of 0.904, a sensitivity of 1.0, and a specificity of 0.237. ConclusionPrecise detection helps to guarantee the precise clinical treatment of patients with hepatitis B cirrhosis and improve their treatment outcome and prognosis. An ALT level of 29 IU/L is a sensitive indicator for predicting patients with negative Cobas HBV DNA, so as to achieve individualized precise screening and treatment.
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Objective To evaluate the efficacy and safety of urinary diversion in patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS).Methods Clinical data of 15 female patients who underwent urinary diversion treatment for IC/BPS in our hospital from January 2008 to July 2018 were retrospectively analyzed.The mean age of the subjects was 64 years old (range 29-79),and the mean disease history of IC/BPS was 5 years (range 2-15).Behavior therapy,oral medicine therapy,intravesical instillation,bladder submucosal injection of botulinum toxin type A and sacral neuromodulation showed unsatisfied outcomes in these patients.Before the surgical intervention,the average urinary frequency was (30.7 ± 11.6) per day,the median visual analogue scale (VAS) was 95 (range 50-100),the O'Leary-Sant Index was 35 (range 31-36) [all the interstitial cystitis problem index (ICPI) was 16],the pelvic pain and urgency/frequency patient symptom scale (PUF) was 35 (range 32-36) [the bother score was 12 (range 11-12)],all the quality of life (QOL) was 6,and the average serum creatinine was (81.1 ± 13.5) μmol/L.Two patients underwent cutaneous ureterostomy without cystectomy,1 patient underwent ileal conduit urinary diversion without cystectomy,and the other 12 patients underwent laparoscopic ileal conduit urinary diversion with cystectomy.The differences of the Global Response Assessment (GRA),complications,VAS,ICPI,PUF,QOL and the serum creatinine before and after the operation were compared.Results The mean postoperative follow-up period was 24 months (range 6-110).The last follow-up showed that all the GRA was 7,the median VAS was 0 (range 0-30),all the ICPI was 0,all the PUF(bother score)was 0,and the median QOL was 2 (1-4),which were significantly different with those before the surgery (all P ＜ 0.01).The last follow-up showed that the average serum creatinine was (83.8 ± 12.5)μ mol/L,which were not significantly different with that before the surgery (P =0.22).Postoperative adhesive intestinal obstruction occurred in 3 subjects.Conclusions Urinary diversion might be an effective and adequate treatment for refractory IC/BPS to eliminate pain or lower urinary tract symptom and improve quality of life of the patients.
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Objective To investigate the duration of indwelling ureteral stent after the ureteroscopic lithotripsy.Methods 300 cases of patients were retrospectively analyzed from June 2015 to June 2017,including 168 with renal calculi and 132 with non-incarcerated upper ureteral calculi.The size of stone is ＜2 cm in diameter.According to the length of time for indwelling ureteral stent,all patients were divided into two groups-150 cases in 14-day group (Group A) and 150 in the 28-day group (Group B) for comparing the complication and outcome,and then received modular flexible ureteroscopic lithotripsy combined with holmium laser.Lastly,6F ureteral stent was indwelling postoperatively.Results Complications happened in both two groups after stenting.There were 140 cases (93.3％) complained of bladder irritation symptoms (LUTS) in Group A,while 107 (71.3％) in Group B;85 cases (56.7％) suffered from flank or abdominal pain in Group A and 36 (24％) in Group B;gross hematuria happened in 133 cases (88.7％) of Group A and 60 cases (40％) of Group B.As the duration of indwelling ureteral stent extended,the incidence of complications increased,significantly (P ＜ 0.05).CT scan showed there was no statistical difference in stone-free rate (diameter ＜ 3 mm) of two groups [A group:91.3 ％ (137/150) vs.B group:89.3 ％ (134/150),respectively].Conclusion With high stone-free rate and low complication incidence,2-week indwelling ureteral stent is safe for patients suffered from renal calculi or non-incarcerated upper ureteral calculi (diameter ＜ 2 cm).
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Objective To summarize the initial treatment experiences of SNM on non-neurogenic,non-obstructive dysuria during short follow-up.Methods From January 2013 to May,2017,28 patients with non-neurogenic,non-obstructive dysuria who were diagnosed by video-urodynamic study (including 20 male patients and 8 female patients;17 patients suffered from urethra sphincter spasm and 11 from idiopathic detrusor weakness) were recruited in our study.All of them received ⅠnterStim sacral neuromodulation treatment.We tried to compare the data (such as frequency in 24 hours,residual urine,dysuria degree,nocturia,average volume and urgency) before operation and the data of short term follow-up after stage Ⅱ implanted pulse generator (IPG) embedded in order to summarize the initial experiences of sacral neuromodulation for non-neurogenic,non-obstructive dysuria.Results All 28patients received stage Ⅰ operation with percutaneous approach to implant a tined lead,11 patients (8 male patients and 3 female patients) finally removed the tined lead because of poor testing effects.17 patients (12 male patients and 5 female patients) choose embedding IPG at the end of stage Ⅰ.Of all these patients,the conversion rate of stage Ⅰ to stage Ⅱ is 60.7％ (17/28),among them,the conversion rate of urethra sphincter spasm is 64.7％ (11/17) and the conversion rate of idiopathic detrusor weakness is 54.5％ (6/11).The follow-up time after stage Ⅱ was16.7 months (10-46 months).The data of voiding frequency in 24 hours,residual urine,dysuria degree,nocturia,urgency,average voiding amount and quality of life (QOL) between baseline (before stage Ⅰ) and at the follow-up time were 16.3 ± 6.1 vs.8.8 ± 4.1 (P =0.000),(43.0 ± 73.4) ml vs.(37.867.1)ml(P=0.178);7.8 ±2.3vs.4.3 ±1.2(P=0.001);4.0± 1.8 vs.2.5 ±1.7(P=0.003),3.1±1.7vs.1.9±1.1(P=0.001),(145.7 ±73.5)ml vs.(189.0±66.4)ml(P=0.48),5.7vs.1.4 (P ＜ 0.05) and 5.4 ± 0.7vs.4.0 ± 1.0 (P =0.000),respectively.During the follow-up period,11 patients satisfied with symptoms relieve without recurrence.Six patients had symptoms recurrence,4/6 patients regain the effects after reprogramming,but two patients remained serious recurrence even after repeated reprogramming(frequency,dysuria and hesitation recurred as before SNM).Conclusions SNM is an effective,safe and minimally invasive procedure for patients with non-neurogenic,non-obstructive dysuria.Primary,non-neurogenic urinary sphincter spasm is a good indication for SNM and had high transfer rate.
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Objective To explore biological characteristics of chondrogenic differentiation of human periosteum-derived cells and the role of BMP4 in chondrogenic differentiation of these cells.Methods From October 2009 to September 2012,periosteum was obtained from tibia of patients undergoing leg amputation surgery,and isolated periosteum-derived cells by tissue culture method.Cells were cultured in DMEM/F12 containing 10％ fetal bovine serum,and morphology of cells were observed under inverted microscope.Periosteum-derived cells growth and the effect of BMP4 on cells growth examined by cell count using trypan blue,and cells growth curve was made.Experiment was divided into control group,chondrogenic differentiation group and BMP4 group,cells were expanded and differentiated in the presence or absence of BMP4 and complete medium.Then toluidine and immunohistochemical staining analyzed proteoglycan and collagenⅡ expression of these cells after 14 and 21 days.The expression of aggrecan,collagen Ⅱ and SOX9 mRNA of these cells using real-time PCR.Results (1) Periosteumderived cells adhered to growth in vitro,the shape of cell presented fibroblast-like morphology changing into polygonal after 1 week and round cell formation after 2 weeks chondrrogenic differemtiation.Growth curve showed that the passage 3 and 9 cells had similar reproductive activity.The passage 3 cells were positive for CD90 (21.07％) and CD105 (25.84％).(2)Toluidine bule staining and type Ⅱ collagen immunohistochemical staining showed BMP4 group (40.29 ± 4.29,56.74 ± 5.12) and chondrogenic differentiated group (19.27 ± 3.71,38.31 ± 4.25) ccould secrete proteoglycan and collagen Ⅱ,control group were negative (10.24 ± 1.21,15.28 ± 2.23),BMP4 group were significantly than chondrogenic differentiated group.(3) The expression of aggrecan,collagen Ⅱ and SOX9 mRNA of BMP4 group(25.76 ±0.57,6.48 ±0.48,2.91 ±0.18)were significantly higher than that of control group(2.37 ±0.24,1.12 ± 0.31,1.07 ± 0.22)and chondrogenic differentiated group(11.12 ± 0.38,2.24 ± 0.41,1.54 ± 0.35)using real-time PCR.Conclusion Periosteum-derived cells have strong proliferative,and have good potentials of differentiating into chondroblasts like mesenchymal stem cells.BMP4 can promote chondrogenic differentiation of periosteum-derived cells in vitro cultures.
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Objective To investigate the changes of 4 histamine receptors (H1R, H2R, H2R and H4 R)in interstitial cystitis on animal experimental models. Methods Thirty female SD rats (250-300 g) were randomly divided into 2 groups as follows: 20 in experimental group and 10 in control group. The experimental group was filled with protamine sulfate+ potassium chloride to create interstitial cystitis model, the control group was sacrificed directly. At the end of the experiment, the bladders of all these SD rats were studied by the immunohistochemistry staining and the value of their mean absorbance (-A) was calculated by IPP4.5 image analysis software. The SPSS 11.5 was used to analyze the differences between the groups. Results Four kinds of histamine receptors mainly expressed in the bladder epithelium. In the experimental group, the (-A) of H1 R was 0. 054±0.031, the of H2R was 0.032±0.021, the (-A) of H3R was 0.047±0.033 and the (-A) of H4R was 0. 149±0. 191,respectively. In the control group, the A of H1R was 0. 017±0. 011, the (-A) of H2R was 0. 018±0. 015, the (-A) of H3R was 0. 014±0. 011, the (-A) of H4R was 0. 060±0.039, respectively. In contrast,the A of H1 R, H2 R and H3R in experimental group was increased significantly(P＜0.05); there was no significant change in (-A) of H4R expression(P＞0.05). Conclusions H1, H2 and H3 receptors in rat model interstitial cystitis bladder epithelium have increased and it indicates H1 R, H2R and H3R may be related to interstitial cystitis. H3 R may be a new treatment target of interstitial cystitis.
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Objective To study the role of bone morphogenetic protein-7 in the osteogenic differentiation of periosteal cellsin vitro. Methods Periosteal cells, obtained from adult tibial periosteum, were cultured by routine method in vitro, and divided into two groups. One group cultured with BMP7 and the supplements of 100 nmol dexametasone, 10 mmol b-glycerophosphate and 50 mg/mL L-ascorbic acid (BMP7 group), the other cultured with the supplements alone as the control (control group). Ultrastructure and morphological changes of periosteal cells were observed by contrast phase microscope and electron microscope. In order to test the expression of markers of osteoblastic differantiation in periosteal cells, involved mineralized node and alkaline phosphatase. Each group was tested at the time of 5 d, 10 d, 15 d, 20 d, respectively, using ALP kit stain and Von Kossa stain with 3 samples at each time. Results The periosteal cells cultured by routine method and induced into osteoblast differentiation with BMP7 were both growing well, in vitro. Microscope observations showed that the periosteal cells were spindle-shaped, well-stacked, transparent and three-dimensional in the early stage, and cube-shaped or puncheon shaped in the mitotic phase, gradually became wide shuttle and irregular shape with a lot secretion in telophase. The positive cells were visible by the ALP kit staining and Von Kossa staining of calcium nodules at 5 d, 10 d, 15 d and 20 d in both groups.A difference of positive rate at each time point was found between BMP7 group and control group at 5 d, 10 d, 15 d, 20 d, and the difference was statistically significant (P ＜ 0.01). Conclusion It displayed well regeneration and osteogenesis ability in the periosteal cell. BMP7 has definite osteo-inductive activity, which can obviously enhance the proliferation and ossifyng differentiation of periosteal cells.