Cell therapy has a very promising potential for end-stage liver diseases (ESLD).Fetal liver stem/progenitor cells (FLSPCs) have advantages of safety,high survival and proliferation rates,and a small volume,all which make them ideal for liver disease stem cell therapy.During the early phase of our study,we applied a three-step separation method to enrich FLSPCs and obtained a separation efficiency similar to that of the flow-cell sorting method.Additionally,using a fulminant hepatic failure model in rats,we have demonstrated that FLSPCs can contribute to morphological and functional recovery of the liver.This manuscript will discuss how FLSPCs can be induced to accurately differentiate into hepatocytes and cholangiocytes and how FLSPCs maintain self-renewal.The Notch signaling plays a critical role in regulating the differentiation and self-renewal of many types of stem cells.Our previous findings have shown that the Notch signaling plays an important role in FLSPCs differentiation into hepatocytes.Therefore,the Notch signaling might be involved in the differentiation and self-renewal of FLSPCs.We conducted a study on the regulatory effects and relative molecular mechanisms of the Notch signaling on FLSPCs and found the corresponding interfering target,which might become an index for the clinical application of FLSPCs.

Objective To analyze the activity of the vastus medialis (VM) and vastus lateralis (VL) muscles in the dynamic stabilization of the patella in patients with patellofemoral pain (PFPS) using standard surface electromyographic (sEMG) tests.Methods This comparative study involved 7 patients with PFPS (13 knees) and 10 healthy subjects (20 knees).They performed weight-bearing squat movements,and sEMG was employed to measure the mean amplitude and the time before peak (TBP) of their VM and VL muscles.Results There was no significant difference between the two groups in the ratio of the mean amplitudes of the VM and VL muscles.However,the ratio in both groups in squatting was significantly higher than when simply standing.In the PFPS group the average TBP delay of the VM relative to the TBP of the VL was significantly longer than in the control group during squat movements.Conclusions The delay in the TBP of the VM relative to the VL during squat movements could serve as a standardized test for assessing treatment effect in patients with local factor PFPS.

Objective To investigate the effect of selectively upward placement of acetabular implants on limb length and post?operative function of developmental dysplasia of the hip patients with shortened legs during total hip arthroplasty (THA). Methods Twenty?six cases of developmental dysplasia of the hip received THA between January 2008 and December 2013, in?cluding 12 cases of Crowe typeⅠ, 8 of Crowe typeⅡ, 6 of Crowe typeⅢ. There were 5 males and 21 females with an average age of 62.7 years (range, 36-80 years). The left hip was involved in 9 cases and the right hip in 17 cases. The preoperative mean Har?ris score was 42.30±12.84, and the preoperative mean WOMAC score was 59.08±13.84 at the last follow?up. The anteroposterior X?ray films and CT scan of the pelvis, anteroposterior and lateral X?ray films of the femur, and TraumaCad analysis were conducted routinely preoperation. More than 70%of the bone?implant interface was covered by appropriate upward distance of acetabular im?plant. Results The follow?up time ranged from 6 to 73 months (mean, 36 months). The Harris score improved to 91.18±7.09, and WOMAC score reduced to 9.85±3.75. According to postoperative measurement, affected limb had been lengthened by 0-5 mm in 8 cases, 6-10 mm in 5 cases, 11-15 mm in 5 cases,>15 mm in 7 cases, and shortening increased 1 mm in 1 case, but the average lengthening was 9.23±7.54 mm. The upward distance of acetabular implant was 0-5 mm in 10 cases, 6-10 mm in 7 cases and>10 mm in 9 cases. The average lengthening was 6.60±6.72 mm in patients having 0-5 mm upward distance, 11.90±5.64 mm in patients having 6-10 mm upward distance and 10.11 ± 9.35 mm in patients having>15 mm upward distance, showing no significant differ?ence. The leg length discrepancy was-3.70±6.43 mm in patients having 0-5 mm upward distance, 1.71±6.24 mm in patients having 6-10 mm upward distance and 0.56 ± 7.70 mm in patients having>15 mm upward distance, showing no significant difference. Con?clusion The limb length could be improved by selectively upward placement of acetabular implants in developmental dysplasia of the hip patients with anatomically abnormal acetabulum during THA, with reasonable preoperative design and corrective operation.

Objective To investigate the utilization of ultrasound monitoring the renal blood flow during extracorporeal membrane oxygenation (ECMO).Methods Twentry one cases,who received veinartery ECMO for heart failure,were examinated by bed-side ultrasound before the ECMO initiated,right after the ECMO initiated,each day after the ECMO initiated,and right after the ECMO weaned.The renal interlobar artery peak velocity (Vmax) was measured,and the renal interlobar artery resistant index (RI) was calculated,as well as the values of the serum creatinine (SCr) and blood urea nitrogen (BUN) were recorded.All the data were compared.Results Compared to the variables right after the ECMO initiated,thc Vmax incrcascd (P ＜ 0.05) two days after ECMO initiated and right after the ECMO weaned,while RI (P ＜ 0.05),SCr (P ＜ 0.05) and BUN (P ＜ 0.05) decreased,there being significant differences (P ＜ 0.05).Conclusions While treating patients with extracorporeal membrane oxygenation,the ultrasound can monitoring the renal blood flow effectively,and provide important parameters for the clinical doctors as the basis of the diagnosis and treatment.

BACKGROUND:Previous studies have indicated that resistin stimulates a large set of chemokines in chondrocytes that are known to be important in inflammatory joint lesions.
OBJECTIVE:To further investigate the mechanism of co-regulation roles of transcription and post-transcription in the up-regulation of two chemokine genes CCL3 and CCL4 in chondrocytes in response to resistin.
METHODS:Human chondrocytes, T/C-28a2 and ATDC5 cels were cultured. The function of resistin on the chemokine genes, and the expression of C/EBPβ, nuclear factor-κB isoforms and chondrogenic specific miRNAs were tested by qPCR. The co-regulation of C/EBPβ and nuclear factor-κB was investigated by nuclear factor-κB inhibitor (IKK-NBD) and C/EBPβ inhibitor (SB303580) treatments, and subcelular localization was detected with or without resistin stimulation.
RESULTS AND CONCLUSION:Resistin could increase the expression of chemokine genes independently. Chondrocytes reacted in a non-restrictedly cel-specific manner to resistin; C/EBPβ inhibitor, nuclear factor-κB and some chondrogenic specific miRNAs in a combinatorial manner regulated chemokine gene expression. The activity of C/EBPβ was augmented by a transient increase in activity of nuclear factor-κB, and both transcription factors acted independently on the chemokine genes, CCL3 and CCL4.

Objective To explore the feasibility,reproducibility and reliability of the T 2* MRI technique in quantifying different concentrations of MnCl2water phantoms at 3.0T.Methods The water phantoms with different concentrations of MnCl2underwent T2* imaging at both 1.5T and 3.0T MRI,and repeated imaging at 3.0T MRI after 1 month.A Spearman correlation was used to determine the relationship of T2* values and Mn concentrations,and established the linear regression equations by using the simple linear regression.W ilcoxon signed-rank sum test and Bland-Altman method were used to evaluate the reproducibility of twice T 2* measurements at 3.0T,and the interclass correlation coefficient(ICC)was calculated.Results T2* values of the phantoms were negatively correlated to Mn concentrations(r= -1.000,P<0.001),and R2* values of the phantoms were positively correlated to Mn concentrations(r=1.000,P<0.001). T2* values of the phantoms measured at 3.0T were positively correlated to that measured at 1.5T(r=1.000,P<0.001).The linear regression equation was T2* 3.0T =0.651T2* 1.5T +0.041.There was no statistical difference of T2* values between the two measurements at 3.0T (Z= -1.732,P=0.083),and ICC was 1.000.Conclusion 3.0T MRI is feasible to quantify cardiac iron deposition.

BACKGROUND:The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment.Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament,but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE:To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS:Elastase solution and control buffer were prepared.The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0,0.1,1.0,2.0,5.0,and 10.0 U/mL elastase solution for 6 hours,and other small samples of the same size were soaked in 2 U/mL elastase solution for 0,1,3,6,9,and 12 hours.To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect,histological staining was used to compare the effects of enzyme treatment on tissue structure and composition.The ligament samples were randomly divided into elastase-treated group and PBS group,and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours,respectively.A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION:(1)The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%,and had no significant effect on other mechanical-related components in the tissue.(2)The histological results showed that elastase was able to penetrate the tissue,and the loose degree of tissue increased after treatment.(3)In the mechanical results before and after treatment,the mechanical properties of the PBS group decreased significantly,only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group.(4)The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment,but the low-tension elastic modulus,initial slopes,saturated slopes,and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group.(5)These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament.

Objective:To dynamically monitor the prevalence and trend of dental fluorosis in children in Shandong Province, and to evaluate the prevention and control measures for drinking water-borne endemic fluorosis (referred to as drinking water-borne fluorosis), and to provide scientific basis for the next step.Methods:Totally 40 counties (cities, districts) were selected as project counties (cities, districts) from drinking water-borne fluorosis areas in Shandong Province in 2018, and all counties (cities, districts) were selected in 2019 and 2020, to investigate the situation of water improvement, detect water fluoride content, and investigate the prevalence of dental fluorosis in children aged 8 - 12 years.Results:From 2018 to 2020, the detection rates of dental fluorosis in children aged 8 - 12 years were 10.30% (503/4 884), 8.94% (25 895/289 539) and 8.66% (24 061/277 689), respectively, with statistically significant differences (χ 2 = 27.10, P < 0.001), and the dental fluorosis indexes were 0.21, 0.18 and 0.17, respectively. The total detection rates of dental fluorosis in children of different age groups in the 3 years were 7.26% (6 590/90 775), 7.97% (9 303/116 680), 9.29% (12 167/130 915), 9.29% (12 238/131 670) and 9.95% (10 161/102 072), the differences were statistically significant (χ 2 = 615.71, P < 0.001). In the 3 years, the total detection rate of dental fluorosis was 8.93% (28 101/314 737) in boys and 8.69% (22 358/257 375) in girls, the difference was statistically significant (χ 2 = 10.27, P = 0.001). In 2018 and 2019, the detection rates of dental fluorosis of children aged 8 - 12 years in water fluoride qualified villages [5.74% (235/4 095) and 7.98% (20 200/253 082)] were significantly lower than those in villages with excessive water fluoride [33.97% (268/789) and 15.62% (5 695/36 457), χ 2 = 570.61, 2 283.76, P < 0.001]. Conclusions:The prevalence of dental fluorosis among children aged 8 - 12 years has been effectively controlled, and remarkable results have been achieved in prevention and treatment of drinking water-borne fluorosis in Shandong Province. However, the detection rate of dental fluorosis among children in a few endemic villages is high, so it is necessary to continue to strengthen the monitoring of fluoride content in drinking water and the condition of dental fluorosis among children.

Objective:To analyze the surveillance data of Kashin-Beck disease (KBD) in Shandong Province, master the changes of KBD, and provide scientific basis for formulating prevention and control strategies of KBD and adjustment of the prevention and control focus of KBD.Methods:According to the requirements of the "National KBD Monitoring Plan" and the "Shandong KBD Monitoring Plan", from 2016 to 2020, the disease monitoring was carried out in the villages of KBD areas in Shandong Province, including the number of clinical positive cases, the number of X-ray positive cases, and the number of metaphyseal positive cases. The detection rate was calculated, and the dynamic changes of the disease was analyzed macroscopically.Results:From 2016 to 2020, a total of 1 816 children aged 7 - 12 years were clinically examined in Shandong Province, and no child with KBD was found. A total of 1 224 children were examined by X-ray, among which 1 positive patient was found in 2016 and 2017, respectively, both of whom were metaphyseal changes, with a total detection rate of 0.16%. There were 367 adult patients with KBD in Shandong Province, including 304 patients with grade Ⅰ, 47 patients with grade Ⅱ and 16 patients with grade Ⅲ. All villages in the KBD areas in Shandong Province had reached the elimination standard, with the elimination rate of 100%.Conclusion:No clinical case of KBD is detected in children aged 7 - 12 years in Shandong Province from 2016 to 2020, which has reached the elimination standard and is in a continuous elimination state.

Objective:To evaluate the effect of health education of a three-year special action for prevention and control of drinking water-borne endemic fluorosis (referred to as drinking water-borne fluorosis) in Shandong Province, and to provide basis for formulating health education measures in the next step.Methods:Nineteen of the disease affected counties (cities and districts) were selected as project counties (cities and districts) in key areas for prevention and control of drinking water-borne fluorosis in Shandong Province in 2018, and 50 disease affected counties (cities and districts) were selected in 2019, and the project counties (cities and districts) were expanded to all of the 105 disease affected counties (cities and districts) in Shandong Province in 2020. Three disease affected townships (towns) were selected in each county (city and district), and health education activities on drinking water-borne fluorosis were carried out in Grade 4 to Grade 6 of the central primary schools and the three villages under its jurisdiction. Students and housewives were selected to conduct questionnaire surveys on prevention and control knowledge of drinking water-borne fluorosis before and after health education. The incidence of dental fluorosis among children aged 8 - 12 years was investigated annually in 6 villages (with children aged 8 - 12 years > 50) , where health education activity was implemented and the incidence of dental fluorosis among children was > 30%, water fluoride content was > 1.5 mg/L and water improvement time was < 5 years.Results:After health education, the awareness rates of drinking water-borne fluorosis in fifth grade pupils [92.46% (4 571/4 944) vs 65.80% (3 334/5 067) in 2018; 94.84% (12 897/13 599) vs 73.55% (9 993/13 587) in 2019; 95.59% (30 407/ 31 809) vs 77.52% (24 463/31 557) in 2020] and housewives [94.12% (2 400/2 550) vs 76.04% (1 939/2 550) in 2018; 94.99% (6 412/6 750) vs 72.00% (4 860/6 750) in 2019; 95.53% (16 183/16 941) vs 78.43% (12 971/16 539) in 2020] were significantly improved (χ 2 = 1 070.47, 2 315.27, 4 456.40, 328.25, 1 294.80, 2 174.63, P < 0.05). After health education in 2020, there were significant differences in the correct answer rates of epidemic causes, hazards and preventive measures of drinking water-borne fluorosis in the questionnaire of fifth grade pupils and housewives (χ 2 = 390.78, 164.94, P < 0.05). The awareness rates of drinking water-borne fluorosis in fifth grade pupils and housewives in the eastern region (Qingdao City, Yantai City and Weifang City) were significantly higher than those in the western region (Dezhou City, Liaocheng City and Heze City) before health education (χ 2 = 547.43, 210.12, P < 0.05), and after health education, the awareness rates increased to more than 90%. The detection rate of dental fluorosis in children decreased year by year (χ 2trend = 27.95, P < 0.05). Conclusions:Through implementation of a three-year special action for prevention and control of drinking water-borne fluorosis in Shandong Province, the awareness rate of fluorosis among target populations has been significantly improved. However, it is still necessary for government departments to further increase investment in health education and carry out health education activities in a deep-going way.