Efficacy evaluation and prognostic factors analysis of retinoblastoma based on propensity score inverse probability weighting method / 解放军医学杂志

Objective To evaluate the efficacy of surgery,chemotherapy and surgery combined chemotherapy for retinoblastoma(RB),and analyze the prognostic factors of RB patients.Methods Clinical data of 1188 RB patients registered in the Surveillance,Epidemiology and End Results(SEER)database from January 2000 to December 2019 were retrospectively analyzed.The baseline characteristics of patients treated with surgery,chemotherapy or surgery combined with chemotherapy were balanced by inverse probability of treatment weighting(IPTW).Log-rank test analysis was used to compare the survival probability of patients in the 3 groups,and Cox regression models were used to analyse the factors influencing the prognosis of RB patients.Results A total of 1188 RB cases were included in this study,including 426 cases in surgery group,200 cases in chemotherapy group and 562 cases in surgery combined with chemotherapy group.After IPTW weighting,baseline data such as age,sex and race were balanced(P＞0.05).Log-rank test results showed that the survival curves of the three groups were significantly different before and after weighting(P＜0.05).After weighted,the survival of patients in surgery group was significantly better than that in chemotherapy group and surgery combined chemotherapy group(P＜0.05),and there was no statistical significance between chemotherapy group and surgery combined chemotherapy group(P＞0.05).The weighted patient survival probability at 1st,3rd and 5th years were 99.7%,98.9%and 98.6%in surgery group;97.4%,95.8%and 95.8%in chemotherapy group;and 97.9%,95.8%and 95.0%in surgery combined chemotherapy group.Cox regression analysis showed that compared with surgery group,the specific risk ratio of death was 1.367(95%CI 1.100-1.700)in chemotherapy group and 1.132(95%CI 0.963-1.330)in combined chemotherapy group.Compared with patients with 1 RB lesion,the patient-specific mortality risk ratio for patients with 2 or more RB lesions was 0.399(95%CI 0.268-0.594).Conclusions Patients with RB have higher survival rates probability after treatment.After controlling the influence of age,sex and other factors,the effect of surgery was better among the three treatment methods.Multifocality may be an independent prognostic factor in RB patients.

"Leverage pry-off method" for effective prevention of thermal injury during microwave ablation of benign thyroid nodules / 南方医科大学学报

OBJECTIVE@#To assess the safety and efficacy of"leverage pry-off method"for preventing thermal injury during microwave ablation of benign thyroid nodules.@*METHODS@#From July, 2017 to September, 2019, a total of 348 patients with benign thyroid nodules underwent ultrasound-guided microwave ablation. For protecting from thermal injury during the ablation, "hydrodissection technique" was used in 174 of the patients (admitted from July, 2017 to August, 2018) and "leverage pry-off method" in the other 174 patients (admitted from September, 2018 to September, 2019). All the patients were followed up for 1 to 12 months after the operation for observation of severe complications and nodular residues.@*RESULTS@#Ultrasound-guided microwave ablation was completed in all the 348 patients. The most common severe complication associated with the ablation was voice change, occurring in 3 cases (1.7%) in "hydrodissection technique" group and in 4 (2.3%) in the "leverage pry-off method" group, showing no significant difference between the two groups (P>0.05). During the follow-up, no significant difference was found in the rate of nodular residues between the "hydrodissection technique" group and "hydrodissection technique" group (9.8% vs 10.9% (P>0.05).@*CONCLUSIONS@#The "leverage pry-off method" is simple and effective for preventing thermal injury during microwave ablation of benign thyroid nodules.

Effects of CACNA1H gene knockout on autistic-like behaviors and the morphology of hippocampal neurons in mice / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effects of CACNA1H gene knockout (KO) on autistic-like behaviors and the morphology of hippocampal neurons in mice.@*METHODS@#In the study, 25 CACNA1H KO mice of 3-4 weeks old and C57BL/6 background were recruited as the experimental group, and 26 wild type (WT) mice of the same age and background were recruited as the control group. Three-chamber test and open field test were used to observe the social interaction, anxiety, and repetitive behaviors in mice. After that, their brain weight and size were measured, and the number of hippocampal neurons were observed by Nissl staining. Furthermore, the CACNA1H heterozygote mice were interbred with Thy1-GFP-O mice to generate CACNA1H-/--Thy1+(KO-GFP) and CACNA1H+/+-Thy1+ (WT-GFP) mice. The density and maturity of dendritic spines of hippocampal neurons were observed.@*RESULTS@#In the sociability test session of the three-chamber test, the KO mice spent more time in the chamber of the stranger mice than in the object one (F1, 14=95.086, P < 0.05; Post-Hoc: P < 0.05), without any significant difference for the explored preference index between the two groups (t=1.044, P>0.05). However, in the social novelty recognition test session, no difference was observed between the time of the KO mice spend in the chamber of new stranger mice and the stranger one (F1, 14=18.062, P < 0.05; Post-Hoc: P>0.05), and the explored preference index of the KO mice was less than that of the control group (t=2.390, P < 0.05). In the open field test, the KO mice spent less time in the center of the open field apparatus than the control group (t=2.503, P < 0.05), but the self-grooming time was significantly increased compared with the control group (t=-2.299, P < 0.05). Morphological results showed that the brain weight/body weight ratio (t=0.356, P>0.05) and brain size (t=-0.660, P>0.05) of the KO mice were not significantly different from those of the control group, but the number of neurons were significantly reduced in hippocampal dentate gyrus compared with the control group (t=2.323, P < 0.05). Moreover, the density of dendritic spine of dentate gyrus neurons in the KO-GFP mice was significantly increased compared with the control group (t=-2.374, P < 0.05), without any significant difference in spine maturity (t=-1.935, P>0.05).@*CONCLUSION@#CACNA1H KO mice represent autistic-like behavior, which may be related to the decrease in the number of neurons and the increase in the density of dendritic spine in the dentate gyrus.

Predictive value of impedance of leadless pacemaker during implantation on trend changes of pacing threshold / 中华心血管病杂志

Objective: To explore the predictive value of the impedance measured during leadless pacemaker Micra implantation on the trend of changes of pacing threshold post implantation. Methods: This is a retrospective cross-sectional study. Patients who received implantation of leadless pacemaker Micra at the Second Xiangya Hospital of Central South University from December 2019 to August 2020 were enrolled. The clinical data and the intraoperative electrical parameters during leadless pacemaker implantation were collected. The impedance and pacing threshold data were analyzed at three time points: immediate release, 5-10 min after release, and after traction test. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to analyze the value of the impedance at immediate release on predicting the trend of changes of pacing threshold post implantation. Results: A total of 21 patients (mean age: (72.2±12.5) years, 12 males) were included. The impedance of 21 patients was (798.1±35.3) Ω immediately after implantation, (800.9±35.6) Ω after 5-10 minutes of release, and (883.6±31.7) Ω after traction test. Impedance was similar between the three time points (P>0.05). The threshold was (0.97±0.11) V/0.24 ms immediately after implantation, (0.95±0.12) V/0.24 ms at 5-10 min after the release, and (0.59±0.06) V/0.24 ms after the traction test. The threshold was significantly lower after the traction test than that immediately after release (P=0.003) and than that at 5-10 minutes after release (P=0.008), suggesting a decreased tendency of the threshold over time. According to the analysis of the ROC curve, the immediate impedance after the release ≥680 Ω could predict the ideal pacing threshold after the traction test (AUC=0.989, 95%CI 0.702-0.964, P<0.001), the prediction sensitivity was 87%, and the specificity was 100%. The pacing threshold would be not ideal with the immediate impedance ≤ 520 Ω (95%CI 0.893-1.000, P<0.001), the sensitivity was 100%, and the specificity was 80%. Conclusions: The impedance immediately after the release has predictive value for the changing trend of threshold post leadless pacemaker Micra implantation. Impedance ≥680 Ω immediately after release is often related with ideal pacing threshold after the traction test. In contrast, the impedance ≤ 520 Ω pacing is often related with unsatisfactory threshold after the traction test, therefore, it is recommended to find a new pacing site to achieve the impedance ≥680 Ω immediately after release during leadless pacemaker Micra implantation.

Minimally invasive dissolving microneedles for ocular brinzolamide delivery / 药学学报

The permeation and pharmacodynamics of ocular drugs are influenced by the corneal barrier. Here, a hard-soluble drug, brinzolamide, was selected as the model drug and used for preparation of minimally invasive dissolving microneedles. Brinzolamide was dissolved in ethanol and polyvinylpyrrolidone (PVP) K90 was added and dissolved. The mixture solution was casted into the dissolving microneedles mold and dried and brinzolamide dissolving microneedles (BMN) were obtained after demolding. The stereoscopic and scanning electron microscopic images showed that BMN were conical needles with the height of 750 μm, the bottom diameter of 300 μm, and the inter-tip distance of 500 μm. The dissolving microneedles patch was composed of 10×10 arrays with the area of 1 cm2 and the high drug load of 7.3 mg·cm-2. BMN showed a rapid in vitro drug release with 93% accumulative release at 2 h and the high drug corneal permeation amount of 877 ± 105 μg. BMN exhibited the high mechanical strength of 0.32 N/needle, leading to easy rat corneal insertion with the depth of 200 μm. Moreover, BMN were rapidly dissolved in the cornea, and more importantly, the damaged cornea were quickly self-healed within 24 h. Animal experiments were approved by the Ethics Committee of Beijing Institute of Radiation Medicine, Academy of Military Medical and the experiments were conducted in accordance with relevant guidelines and regulations. Ocular minimally invasive dissolving microneedles have the advantages of corneal minimal wounds and rapid healing, high drug loading, and high permeability, favoring the treatment of ocular diseases.

Clinical Characteristics and Genetic Analysis of Klippel-Feil Syndrome / 中国医学科学院学报

Objective To summarize clinical characteristics and investigate possible pathogenic gene of Klippel-Feil syndrome(KFS)by the self-designed multigene panel sequencing,so as to decipher the molecular basis for early diagnosis and targeted therapy.Methods From January 2015 to December 2018,we consecutively recruited 25 patients who were diagnosed with KFS in Peking Union Medical College Hospital.The demographic information,clinical manifestations,physical examination and radiological assessments were analyzed.Multigene panel sequencing was performed after DNA extraction from peripheral blood.The possible pathogenic mutations of KFS were explored on the basis of bioinformatics analysis.Results The KFS cohort consisted of 25 patients,including 15 males and 10 females,with a mean age of(12.9±7.3)years.Limited cervical range of motion was the most common clinical feature(12 cases,48%).Based on the Samartzis classification,the proportion of patients suffered from short neck(P=0.031)and limited cervical range of motion(P=0.026)in type Ⅲ KFS was significantly higher than that in type Ⅱ and type Ⅰ KFS.Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients,including COL6A1,COL6A2,CDAN1,GLI3,FLNB,CHRNG,MYH3,POR,and TNXB.There was no pathogenic mutation found in five reported pathogenic genes(GDF6,MEOX1,GDF3,MYO18B and RIPPLY2)associated with KFS.Conclusions Our study has shown that patients with multiple contiguous cervical fusions are more likely to manifest short neck,limited cervical range of motion,and clinical triad.Therefore,these patients need additional attention and follow-up.Our analysis highlights novel KFS-related genetic variants,such as COL6A and CDAN1,extending the spectrum of known mutations contributing to this syndrome and providing a basis for elucidating the pathogenesis of KFS.

Plasma levels of receptor interacting protein kinase-3 correlated with coronary artery disease / 中华医学杂志(英文版)

BACKGROUND@#Necroptosis plays an important role in human atherosclerosis and atheroma development. Since receptor interacting protein kinase-3 (RIP3) acts as a key mediator of necroptosis, this study aimed to explore its relationship between plasma RIP3 levels and coronary artery disease (CAD) and discover a potential new biomarker for screening CAD subtypes and severity.@*METHODS@#A total of 318 patients with CAD who had coronary angiography and 166 controls in Peking Union Medical College Hospital from September 2017 to January 2018 were enrolled in this study. Patients with CAD were divided into three subgroups: patients with stable coronary artery disease (SCAD), patients with unstable angina (UA), and patients with myocardial infarction (MI). The severity of atherosclerosis was determined by Gensini score (GSS). Logistic regression was used to determine the relationship between plasma RIP3 levels and CAD. The correlation between plasma RIP3 and GSS was calculated using multiple linear regression models.@*RESULTS@#Overall, plasma RIP3 levels were significantly higher than serum RIP3 levels. Plasma RIP3 levels in patients with CAD were significantly higher than those in controls. Plasma RIP3 levels were strongly associated with CAD (odds ratio: 6.00, 95% confidence interval 3.04-11.81; P < 0.001). Plasma RIP3 levels increased linearly from controls to patients with SCAD, then patients with UA, and finally to patients with MI. We found a significantly positive correlation between proportion of cases of acute coronary syndrome in subjects and their plasma RIP3 level quartile. Plasma RIP3 levels were also associated with GSS (B 0.027; standard error 0.012; P < 0.05).@*CONCLUSIONS@#Plasma RIP3 levels were independently associated with CAD. Plasma RIP3 levels could potentially supplement clinical assessment to screen CAD and determine CAD severity.

Plasma levels of receptor interacting protein kinase-3 correlated with coronary artery disease / 中华医学杂志(英文版)

Background@#Necroptosis plays an important role in human atherosclerosis and atheroma development. Since receptor interacting protein kinase-3 (RIP3) acts as a key mediator of necroptosis, this study aimed to explore its relationship between plasma RIP3 levels and coronary artery disease (CAD) and discover a potential new biomarker for screening CAD subtypes and severity.@*Methods@#A total of 318 patients with CAD who had coronary angiography and 166 controls in Peking Union Medical College Hospital from September 2017 to January 2018 were enrolled in this study. Patients with CAD were divided into three subgroups: patients with stable coronary artery disease (SCAD), patients with unstable angina (UA), and patients with myocardial infarction (MI). The severity of atherosclerosis was determined by Gensini score (GSS). Logistic regression was used to determine the relationship between plasma RIP3 levels and CAD. The correlation between plasma RIP3 and GSS was calculated using multiple linear regression models.@*Results@#Overall, plasma RIP3 levels were significantly higher than serum RIP3 levels. Plasma RIP3 levels in patients with CAD were significantly higher than those in controls. Plasma RIP3 levels were strongly associated with CAD (odds ratio: 6.00, 95% confidence interval 3.04–11.81; P < 0.001). Plasma RIP3 levels increased linearly from controls to patients with SCAD, then patients with UA, and finally to patients with MI. We found a significantly positive correlation between proportion of cases of acute coronary syndrome in subjects and their plasma RIP3 level quartile. Plasma RIP3 levels were also associated with GSS (B 0.027; standard error 0.012; P < 0.05).@*Conclusions@#Plasma RIP3 levels were independently associated with CAD. Plasma RIP3 levels could potentially supplement clinical assessment to screen CAD and determine CAD severity.

Composition analysis,antioxidative and antibacterial activities comparison of agarwood oils extracted by supercritical and steam distillation / 中国中药杂志

Agarwood is a traditional and precious medicinal material and natural spice in China and other southeast Asian countries.As the head of all spices,agarwood has many pharmacological activities such as analgesia,antidiarrheal,anti-inflammatory and antibacterial effects. Due to its high price and scarce resources,there were just a few previous studies on it,mainly focusing on the chemical compositions of the agarwood essential oil and solvent extract mixture. The components of agarwood oils obtained by supercritical extraction and steam distillation were analyzed by using Gas Chromatography-Mass Spectrometer( GC-MS),and then the agarwood oils compositions and contents were compared between the traditional extraction method and the recently emerging supercritical extraction method. Antioxidant experiments of scavenging DPPH,ABTS,hydroxyl radical,total reducing power and MIC experiments of five kinds of tester strains such as staphylococcus aureus were combined to illustrate the differences between these two kinds of agarwood oils in terms of antioxidant and bacteriostatic activities. The results showed that the main components of agarwood oil were sesquiterpenoids( 68. 68%) in steam distillation extraction method,but sesquiterpenoids( 23. 78%) and chromones( 29. 42%) in supercritical extraction method. Fourteen common components included benzyl acetone,α-santalol,γ-eudesmol,agarospirol and guaiol etc. The antioxidant activity and inhibitory MIC of agarwood oils in supercritical extraction method were better than those in steam distillation method,and the inhibitory effect of agarwood oil on the growth of bacillus subtilis was found for the first time.

Lumbar Scoliosis Induction in Juvenile Dogs by Three-dimensional Modulation of Spinal Growth Using Nickel-Titanium Coil Springs / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Current treatments for scoliosis have some defects and complications. To study spinal deformities and test novel scoliosis treatments, many animal models of scoliosis have been developed. These models applied a single load to the spine and could not precisely modulate the spinal growth in different dimensions. In this study, we applied posterior tethering in various directions with the application of nickel-titanium (NT) coil springs in dog's spine to modulate spinal growth in the coronal, sagittal, and transverse planes and create a scoliosis model possess curves that mimic adolescent idiopathic scoliosis (AIS) three dimensionally.</p><p><b>METHODS</b>Scoliosis was surgically induced in eight 8-week-old female dogs (weight: 1.95-2.30 kg) using bone screws and NT coil springs. The deformity was induced through the placement of posterior NT coil springs that tethered the spine by bone screw fixation. All dogs were monitored with serial radiographs to document changes in deformities.</p><p><b>RESULTS</b>All experimental animals developed scoliotic curves convex to the left in the lumbar segment. The mean coronal Cobb angle was 18.0° immediately postoperatively and 54.5° at 22 weeks. The mean lordosis increased from 6.2° postoperatively to 35.0° at final follow-up. Apical axial rotation increased from 4.5° postoperatively to 31.2° at 22 weeks.</p><p><b>CONCLUSIONS</b>With the application of NT springs in dogs that allowed posterior tethering in various directions, lumbar spinal deformity was achieved in three planes: coronal, sagittal, and transverse planes. Notably, the lumbar spine in surgically treated dogs developed lordoscoliosis with obvious rotation and the curves mimic AIS three dimensionally well. This method allows lumbar scoliosis to develop without deep dissection of muscle and maintains the essential anatomical elements along the spinal curve. Moreover, the spinal growth modulation technique could yield information that would provide a basis for developing novel early-stage treatments for children with scoliosis.</p>

Recent Advances in Technique and Clinical Outcomes of Minimally Invasive Spine Surgery in Adult Scoliosis / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Conventional open spinal surgery of adult scoliosis can be performed from anterior, posterior, or combined approach. Minimally invasive spine surgery (MISS) was developed for the purpose of reducing the undesirable effects and complications. This review aimed to make a brief summary of recent studies of the approach and clinical outcomes of MISS in adult scoliosis.</p><p><b>DATA SOURCES</b>We conducted a systematic search from PubMed, Medline, EMBASE, and other literature databases to collect reports of surgical methods and clinical outcomes of MISS in treatment of adult scoliosis. Those reports were published up to March 2017 with the following key terms: "minimally invasive," "spine," "surgery," and "scoliosis."</p><p><b>STUDY SELECTION</b>The inclusion criteria of the articles were as followings: diagnosed with adult degenerative scoliosis (DS) or adult idiopathic scoliosis; underwent MISS or open surgery; with follow-up data. The articles involving patients with congenital scoliosis or unknown type were excluded and those without any follow-up data were also excluded from the study. The initial search yielded 233 articles. After title and abstract extraction, 29 English articles were selected for full-text review. Of those, 20 studies with 831 patients diagnosed with adult DS or adult idiopathic scoliosis were reviewed. Seventeen were retrospective studies, and three were prospective studies.</p><p><b>RESULTS</b>The surgical technique reported in these articles was direct or extreme lateral interbody fusion, axial lumbar interbody fusion, and transforaminal lumbar interbody fusion. Among the clinical outcomes of these studies, the operated levels was 3-7, operative time was 2.3-8.5 h. Both the Cobb angle of coronal major curve and evaluation of Oswestry Disability Index and Visual Analog Scale decreased after surgery. There were 323 complications reported in the 831 (38.9%) patients, including 150 (18.1%) motor or sensory deficits, and 111 (13.4%) implant-related complications.</p><p><b>CONCLUSIONS</b>MISS can provide good radiological and self-evaluation improvement in treatment of adult scoliosis. More prospective studies will be needed before it is widely used.</p>

Treatment of pulmonary sinus cusp-derived ventricular arrhythmia with reversed U-curve catheter ablation / 中国介入心脏病学杂志

Objective To summarize the ablation methods,and to provide experience reference for the treatment of pulmonary since cusp(PSC)-derived ventricular arrhythmia(VA)with ablation. Methods A retrospective analysis of the clinical data of 19 patients undergoing catheter ablation for PSC-derived VA in Cardiac Intervention Therapy Center,The Second Xiangya Hospital of Central South University between January 2013 and March 2016 was conducted. Results Among the 19 patients,PSC-derived VA originated from the lower regions of the pulmonary sinuses,generating from the right,left,and anterior sinuses of the PSC were identified in 5,7,and 7 patients,respectively. Twelve patients with PSC-derived VAs originating from the right and anterior sinuses underwent successful reversed U-curve catheter ablation,while the other 7 patients with arrhythmias originating from the left sinus underwent successful ablation with the conventional method(non-reversed U-curve catheter ablation). All the patients were followed-up for 6 to 31 months,and no recurrence of VA or complications were recorded. Conclusions Reversed U-curve catheter ablation is suitable for VA originating from the right and anterior PSCs,while conventional ablation can be used for those originating from the left PSCs.

Effect of Resveratrol on Preventing Steroid-induced Osteonecrosis in a Rabbit Model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Prevention of osteonecrosis (ON) has seldom been addressed. The purpose of this study was to evaluate the effect of resveratrol on preventing steroid-induced ON in rabbits.</p><p><b>METHODS</b>Seventy-two rabbits were divided into four groups: (1) NEC (ON) group: thirty rabbits were treated with lipopolysaccharide (LPS) once, then with methylprednisolone (MPS) daily for 3 days; (2) PRE (prevention) group: thirty rabbits were given one dose of LPS, then MPS daily for 3 days, and resveratrol on day 0 and daily for 2 weeks; (3) RES (resveratrol) group: six rabbits were given resveratrol for 2 weeks but without LPS/MPS; (4) CON (control) group: six rabbits were given alcohol for 2 weeks but without LPS/MPS. Levels of plasma tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), thrombomodulin (TM), vascular endothelial growth factor (VEGF), maximum enhancement (ME) by magnetic resonance imaging, and ON incidence were evaluated.</p><p><b>RESULTS</b>The PRE group had a lower ON incidence than the NEC group, but with no significant differences at 2 weeks and 12 weeks. The RES and CON groups did not develop ON. TM and VEGF were significantly higher in the NEC group compared with the PRE group at weeks 1, 2, and 4 (TM: 1 week, P = 0.029; 2 weeks, P = 0.005; and 4 weeks, P = 0.047; VEGF: 1 week, P = 0.039; 2 weeks, P = 0.021; 4 weeks, P = 0.014), but the difference disappeared at 12 weeks. The levels of t-PA and PAI-1 were not significantly different between the NEC and PRE groups. The TM, t-PA, PAI-1, and VEGF concentrations in the RES and CON groups did not change over time. Compared to the baseline, ME in the NEC group decreased significantly (P = 0.025) at week 1, increased significantly (P = 0.021) at week 2, and was decreased at week 12. The variance was insignificant in the PRE group.</p><p><b>CONCLUSIONS</b>Resveratrol may improve blood supply to bone in a rabbit model of ON of the femoral head via anti-inflammatory effects to protect the vascular endothelium and reduce thrombosis.</p>

Dynamic Expression Profiles of Marker Genes in Osteogenic Differentiation of Human Bone Marrow-derived Mesenchymal Stem Cells / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To observe the expression profiles of osteoblast-related genes in human mesenchymal stem cells (MSCs) derived from bone marrow during osteogenic differentiation.</p><p><b>METHODS</b>MSCs were induced to differentiate with MSC osteogenic differentiation medium for 7, 14, 21 and 28 days respectively. Alizarin Red staining was used to detect matrix mineralization. Expression of osteoblast-related genes, including osteocalcin, osteopontin, Runt-related transcription factor 2 (Runx2), alkaline phosphatase and collagen type 1, was assessed with quantitative reverse transcription-polymerase chain reaction.</p><p><b>RESULTS</b>On day 14 after induction of differentiation, cells were stained positively with Alizarin Red. The expression levels of these genes exhibited an upward trend as induction time was prolonged. Exposure to osteogenic differentiation medium less than 21 days did not significantly induce osteocalcin expression; osteocalcin expression levels in the differentiated cells induced for 21 and 28 days were 1.63 and 2.46 times as high as the undifferentiated cells respectively (all P<0.05). Stimulation with MSC osteogenic differentiation medium over 14 days significantly enhanced bone marrow-derived MSCs to express osteopontin and Runx2 genes (all P<0.05). Osteogenic differentiation medium could significantly induce the expressions of alkaline phosphatase and collagen type1 genes (all P<0.05). Their expressions reached the peak levels on day 21, which were increased more than 4- and 3-fold respectively.</p><p><b>CONCLUSION</b>Human bone marrow-derived MSCs could exhibit the sequential expression pattern of osteoblast marker genes during osteogenic differentiation in vitro.</p>

Reliability of a novel Cobb protractor for measuring the Cobb angle of radiograph in scoliosis / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To introduce a novel Cobb protractor and assess its reliability and rapidity for measuring Cobb angle in scoliosis patients.</p><p><b>METHODS</b>The novel Cobb protractor had two endplate markers. A measurement was performed just to align the two markers to each endplate of the curve. The Cobb angle on the posteroanterior radiographs of 24 patients clinically diagnosed with adolescent idiopathic scoliosis was measured by three orthopedic surgeons with both standard Cobb method and the new technique, and the time of measurement was recorded. Intraclass correlation coefficients (ICCs) were calculated to assess the reliability of the new method.</p><p><b>RESULTS</b>The time for a measurement with the new tool was approximately 10 seconds less than the time that used to finish a measurement with the standard method (P<0.05). The overall mean Cobb angle for the major curve of the 24 patients was 47.8°. The mean overall intraobserver and interobserver ICC was 0.971 and 0.971 for the Cobb method group, while the overall intraobserver ICC and the interobserver was 0.985 and 0.979 for the new tool group.</p><p><b>CONCLUSIONS</b>The novel Cobb protractor could perform quick measurement and measure almost all forms of radiographs. The Cobb protractor might be an ideal instrument to measure the Cobb angle.</p>

Localized Scleroderma of Lower Extremities:Clinical and Magnetic Resonance Imaging Features / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the clinical and musculoskeletal characteristics of localized scleroderma with lower extremities affected.</p><p><b>METHODS</b>All the localized scleroderma patients,who received magnetic resonance (MR ) examinations of affected lower extremities at Peking Union Medical College Hospital from April 2013 to June 2014,were retrospectively reviewed. Their clinical data and laboratory results of antinuclear antibody,anti-double stranded-DNA antibody, and anti-extractable nuclear antigen antibody were collected and analyzed. All the MR examinations were non-contrast imaging using Siemens Skyra 3.0T MR scanner.</p><p><b>RESULTS</b>There were 16 localized scleroderma patients with lower extremities affected, 11 of whom were linear scleroderma, 4 generalized morphea, and 1 deep morphea. Female to male ratio was 1:2.2. The mean age was 22.5 years. The mean time span was 7.4 years. Four of the 14 patients (28.6%) who received antinuclear antibody test were positive. All the 10 patients who received anti-double stranded-DNA antibody test and the 7 patients who received anti-extractable nuclear antigen antibody test were negative. The most common musculoskeletal MR features were subcutaneous septal thickening (16/16) and fascial thickening (11/16). The thickened speta and fascia could either be hypointenstiy or hyperintensity on turbo inversion recovery magnitude/proton density weighted imaging. Other MR manifestations were intramuscular speta thickening (3/16), muscular abnormal signals (1/16), and bone marrow abnormal signals (2/16).</p><p><b>CONCLUSION</b>Musculoskeletal manifestations of the lower extremities with localized scleroderma can be well revealed using MR imaging.</p>

Advances in minimally invasive spine surgery in treatment of adolescent idiopathic scoliosis and adult scoliosis / 中国医学科学院学报

The traditional treatment of scoliosis is mainly based on open surgeries that use the anterior approach, the posterior approach, or both. These surgical procedures often lead to complications including massive blood loss, infections, and pain of incision.The minimally invasive spine surgery (MISS) was introduced in the 1990s and has shown many advantages including less blood loss, less pain, and lower infection incidences.Today MISS is mainly used in the treatment of adolescent idiopathic scoliosis and adult scoliosis. However, due to some inevitable complications, it still can not be routinely applied.This review will briefly summarize the advances in the application of MISS in surgical treatment of adolescent idiopathic scoliosis and adult scoliosis.

Efficacy observation on knee osteoarthritis treated with electroacupuncture and its influence on articular cartilage with T2 mapping / 中国针灸

<p><b>OBJECTIVE</b>To observe therapeutic efficacy of osteoarthritis treated by electroacupuncture, and explore its function of promoting cartilage restoration.</p><p><b>METHODS</b>According to random digital table, sixty cases of knee osteoarthritis (60 knees) were randomly divided into an electroacupuncture group and a physiotherapy group, 15 cases (30 knees) in each one. The electroacupuncture was applied at Neixiyan (EX-LE 4), Dubi (ST 35), Heding (EX-LE 2) and Xuehai (SP 10) in the electroacupuncture group, once every other day. The physiotherapy group was treated by medium-frequency therapeutic apparatus every day. For both groups, 4 weeks of treatment were required. The Lysholm knee scoring scale (LKSS) was used to evaluate and compare the knee joints function before and after treatment. At the same time, the GE Signa EXCITE Twin Speed HD 1.5T was used to take MRI examination of knee joints, and measure the T2 values in 10 sub-regions of the cartilage of tibiofemoral joints.</p><p><b>RESULTS</b>Compared before treatment, the LKSS score of both groups were improved with significant differences except item demands for support (P < 0.01, P < 0.05). Between the two groups after treatment, there were significant differences on total score, item instability and swelling (all P < 0.05), the electroacupuncture group was better than the physiotherapy group, but no significant difference on the other items (all P > 0.05). In the electroacupuncture group after treatment, T2 value in anterior lateral tibial sub-region (LTa) was significantly lowered (P < 0.05), but no significant difference in the other nine sub-regions (all P > 0.05). In the physiotherapy group, T2 value in any sub-region was not significantly different before and after treatment (all P > 0.05).</p><p><b>CONCLUSION</b>Electroacupuncture could effectively improve the symptom, sign and knee joint's function of patients with knee osteoarthritis. Compared with physiotherapy, it has more superior effect and considered as a better non-operative treatment for osteoarthritis. Electroacupuncture also has positive influence on T2 value in cartilage, indicating that electroacupuncture may have the function of promoting cartilage restoration.</p>

Increase of TNFα-stimulated osteoarthritic chondrocytes apoptosis and decrease of matrix metalloproteinases 9 by NF-κB inhibition / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-κB inhibitor, on the apoptosis of osteoarthritic (OA) chondrocytes and on the regulation of the gelatinases matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9).</p><p><b>METHODS</b>Annexin V-FITC/propidium iodide (PI) labeling and western blotting were used to observe and determine the apoptosis in TNFα-stimulated primary cultured osteoarthritic chondrocytes. Also, gelatin zymography was applied to examine MMP-2 and MMP-9 activities in supernatants.</p><p><b>RESULTS</b>It was confirmed by both flow cytometry and western blotting that chondrocytes from OA patients have an apoptotic background. Use of CAPE in combination with 10 ng/mL of TNFα for 24 h facilitated the apoptosis. MMP-9 in the supernatant could be autoactivated (from proMMP-9 to active MMP-9), and the physiologic calcium concentration (2.5 mmol/L) could delay the autoactivation of MMP-9. The activities of MMP-2 and MMP-9 in the fresh supernatant increased significantly in response to stimulation by 10 ng/mL of TNFα for 24 h. The stimulatory effect of TNFα just on proMMP-9 was counteracted significantly by CAPE.</p><p><b>CONCLUSION</b>NF-κB could prevent chondrocytes apoptosis though its activation was attributed to the increase of proMMP-9 activity induced by TNFα (a pro-apoptotic factor). Therefore, therapeutic NF-κB inhibitor was a 'double-edged swords' to the apoptosis of chondrocytes and the secretion of MMP-9.</p>

Adiponectin receptor 1 mediates the difference in adiponectin- induced prostaglandin E2 production in rheumatoid arthritis and osteoarthritis synovial fibroblasts / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The synovial fluid concentrations of adiponectin are significantly higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA). Accumulating evidence suggests that adiponectin may be an inducer of inflammation in arthritis, but the mechanism remains unclear. The objectives of this study were to compare the expression levels of adiponectin receptors in rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF), evaluate the roles of adiponectin receptors in adiponectin-induced prostaglandin E(2) (PGE(2)) production, and then investigate the effects of a nonsteroidal anti-inflammatory drug (NSAID) and a cyclooxygenase (COX)-2-selective inhibitor on adiponectin-induced PGE(2) release.</p><p><b>METHODS</b>The expressions of adiponectin receptor 1 (AdipoR1) and AdipoR2 mRNA and protein in synovial fibroblasts from seven patients with RA and eight patients with OA undergoing total knee replacement were evaluated by real-time polymerase chain reaction, immunofluorescence microscopy and Western blotting analysis. Adiponectin-induced PGE(2) production was detected by enzyme-linked immunosorbent assay. RNA interference against the AdipoR1 and AdipoR2 genes was performed to investigate the effects of the adiponectin receptors on adiponectin-induced PGE(2) production in both RASF and OASF.</p><p><b>RESULTS</b>AdipoR1 and AdipoR2 mRNA and protein were expressed by both RASF and OASF. Compared with OASF, RASF exhibited higher levels of AdipoR1, but there was no significant difference for AdipoR2. Adiponectin induced the production of PGE(2) by the synovial fibroblasts in a concentration-dependent manner, and this was more obvious in RASF. RNA interference showed that the difference may be mediated by the diverse distribution of AdipoR1. The adiponectin-induced PGE(2) production was efficiently relieved by the NSAID and COX-2-selective inhibitor.</p><p><b>CONCLUSION</b>The present findings suggest that AdipoR1 may mediate the difference in adiponectin-induced PGE(2) production in RASF and OASF.</p>