Wnt/b-Catenin Promotes the Osteoblastic Potential of BMP9 Through Down-Regulating Cyp26b1 in Mesenchymal Stem Cells

BACKGROUND@#All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. @*METHODS@#ATRA content was detected with ELISA and HPLC–MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro–computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. @*RESULTS@#We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/b-catenin, and reduced by inhibiting this pathway. b-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. @*CONCLUSIONS@#Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.

The effects of robotic-assisted versus laparoscopic-assisted radical right hemicolectomy on short-term outcome and long-term prognosis based on propensity score matching / 中华外科杂志

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ2 test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.

Performance of the Combined Model Based on Both Clinicopathological and CT Texture Features in Predicting Liver Metastasis of High-risk Gastrointestinal Stromal Tumors / 中国医学科学院学报

Objective To investigate the performance of the combined model based on both clinicopathological features and CT texture features in predicting liver metastasis of high-risk gastrointestinal stromal tumors(GISTs). Methods The high-risk GISTs confirmed by pathology from January 2015 to December 2020 were analyzed retrospectively,including 153 cases from the Cancer Hospital of the University of Chinese Academy of Sciences and 51 cases from the Shaoxing Central Hospital.The cases were randomly assigned into a training set(n=142)and a test set(n=62)at a ratio of 7∶3.According to the results of operation or puncture,they were classified into a liver metastasis group(76 cases)and a non-metastasis group(128 cases).ITK-SNAP was employed to delineate the volume of interest of the stromal tumors.Least absolute shrinkage and selection operator(LASSO)was employed to screen out the effective features.Multivariate logistic regression was adopted to construct the models based on clinicopathological features,texture features extracted from CT scans,and the both(combined model),respectively.Receiver operating characteristic(ROC)curve and calibration curve were established to evaluate the predictive performance of the models.The area under the curve(AUC)was compared by Delong test. Results Body mass index(BMI),tumor size,Ki-67,tumor occurrence site,abdominal mass,gastrointestinal bleeding,and CA125 level showed statistical differences between groups(all P<0.05).A total of 107 texture features were extracted from CT images,from which 13 and 7 texture features were selected by LASSO from CT plain scans and CT enhanced scans,respectively.The AUC of the prediction with the training set and the test set respectively was 0.870 and 0.855 for the model based on clinicopathological features,0.918 and 0.836 for the model based on texture features extracted from CT plain scans,0.920 and 0.846 for the model based on texture features extracted from CT enhanced scans,and 0.930 and 0.889 for the combined model based on both clinicopathological features and texture features extracted from CT plain scans.Delong test demonstrated no significant difference in AUC between the models based on the texture features extracted from CT plain scans and CT enhanced scans(P=0.762),whereas the AUC of the combined model was significantly different from that of the clinicopathological feature-based model and texture feature-based model(P=0.001 and P=0.023,respectively). Conclusion Texture features extracted from CT plain scans can predict the liver metastasis of high-risk GISTs,and the model established with clinicopathological features combined with CT texture features has best prediction performance.

Screening status of retinopathy of prematurity in China / 国际眼科杂志(Guoji Yanke Zazhi)

@#Retinopathy of prematurity(ROP)is an avoidable and controllable oculopathy of blindness and low vision in children. Screening is the premise and a key measure for early detection, intervention and treatment. It is of great significance to reducing the blindness rate and visual impairment of children. The main of this review is to review the current situation on screening and morbidity of ROP in China, and to provide reference for preventive and treatment of ROP.

Impact of Laparoscopic Versus Open Hepatectomy on Perioperative Clinical Outcomes of Patients with Primary Hepatic Carcinoma / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To compare the perioperative outcomes of patients with primary hepatic carcinoma treated with laparoscopic hepatectomy (LH) with those treated with open hepatectomy (OH).</p><p><b>METHODS</b>From January 2010 to August 2014, 100 patients with primary hepatic carcinoma were randomly divided into the LH group and OH group respectively, 50 patients in each group. And the incision length, blood loss, operative time, postoperative liver function, anus exhaust time, complications, length of postoperative hospital stay, and cost measures were compared.</p><p><b>RESULTS</b>LH could achieve shorter incision length, less blood loss, more rapid recovery in liver function and gastrointestinal function, and shorter postoperative hospital stay length compared with OH for primary hepatic carcinoma patients (all P<0.05). However, LH could not significantly shorten operative time, and reduce postoperative complications and hospitalization cost (all P>0.05).</p><p><b>CONCLUSION</b>Compared with OH, LH could improve perioperative outcomes of primary hepatic carcinoma patients.</p>

Influence of Photodynamic Therapy on Apoptosis and Invasion of Human Cholangiocarcinoma QBC939 Cell Line / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the effect of photodynamic therapy (PDT) mediated by hematoporphyrin derivative (HPD) on apoptosis and invasion of cholangiocarcinoma QBC939 cell lines.</p><p><b>METHODS</b>In vitro cultured cholangiocarcinoma QBC939 cell line was exposed to 2, 4, 6, 8, 10, 12, and 14 μg/ml HPD with 5, 10, and 15 J/cm2 light intensity, respectively. The optical density at 450 nm of the QBC939 cells was measured by CCK8 assay and its growth inhibition ratio was calculated. Flow cytometry and transwell migration assay were applied to detect cell apoptosis and invasion respectively. RT-PCR and immunocytochemistry analyses were used to detect expressions of vascular endothelial growth factor-C (VEGF-C), cyclooxygenase-2 (COX-2), and proliferating cell nuclear antigen (PCNA). Enzyme-linked immunosorbent assay (ELISA) was carried out to examine the secretion of VEGF-C and COX-2 in QBC939 cells.</p><p><b>RESULTS</b>Exposure to HPD-PDT can significantly suppress the growth of QBC939 cells (all P<0.05). HPD-PDT can promote apoptosis of QBC939 cells at the early stage. When the concentration of HPD was 2 μg/ml and light irradiation was 5 J/cm2, HPD-PDT had no obvious inhibitory effect on QBC939 cell growth, but can obviously inhibit cell invasion, and significant difference was observed between the HPD-PDT and control groups (P<0.01). The HPD-PDT can reduce the mRNA and protein expressions of VEGF-C, COX-2, and PCNA, and decrease the secretion of VEGF-C and COX-2 in QBC939 cells.</p><p><b>CONCLUSION</b>PDT could promote apoptosis and inhibit growth and invasion of cholangiocarcinoma cells QBC939 in vitro.</p>

Effect of alemtuzumab on intestinal intraepithelial lymphocytes and intestinal barrier function in cynomolgus model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Alemtuzumab has been used in organ transplantation and a variety of hematologic malignancies (especially for the treatment of B-cell chronic lymphocytic leukemia). However, serious infectious complications frequently occur after treatment. The reason for increased infections postalemtuzumab treatment is unknown at this stage. We explore the effect of alemtuzumab on intestinal intraepithelial lymphocytes (IELs) and intestinal barrier function in cynomolgus model to explain the reason of infection following alemtuzumab treatment.</p><p><b>METHODS</b>Twelve male cynomolguses were randomly assigned to either a treatment or control group. The treatment group received alemtuzumab (3 mg/kg, intravenous injection) while the control group received the same volume of physiological saline. Intestinal IELs were isolated from the control group and the treatment group (on day 9, 35, and 70 after treatment) for counting and flow cytometric analysis. Moreover, intestinal permeability was monitored by enzymatic spectrophotometric technique and enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>The numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 × 10 8 and 1.35 ± 0.09 × 10 8 , respectively; P < 0.05) and were not fully restored until day 70 after treatment. There were significant differences among four groups considering IELs subtypes. In addition, the proportion of apoptotic IELs after alemtuzumab treatment was significantly higher than in the control group (22.01 ± 3.67 and 6.01 ± 1.42, respectively; P < 0.05). Moreover, the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment.</p><p><b>CONCLUSIONS</b>Alemtuzumab treatment depletes lymphocytes in the peripheral blood and intestine of cynomolgus model. The induction of apoptosis is an important mechanism of lymphocyte depletion after alemtuzumab treatment. Notably, intestinal barrier function may be disrupted after alemtuzumab treatment.</p>

The regulatory mechanism of songling xuemaikang capsule on PPARgamma in spontaneously hypertensive rats: an experimental study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Songling Xuemaikang Capsule (SXC) on blood pressure of spontaneously hypertensive rats (SHR) and regulatory mechanisms for peroxisome proliferator activated receptor-gamma (PPARgamma).</p><p><b>METHODS</b>Totally 24 10-week-old SHR rats were randomly divided into the blank control group, the Chinese medicine (CM) group, and the Western medicine (WM) group, 8 in each group. Rats in the CM group were administered with SXC at the daily dose of 20 mg/kg by gastrogavage. Those in the WM group were administered with ramipril at the daily dose of 1 mg/kg by gastrogavage. Those in the blank control group were administered with equal volume of normal saline. The blood pressure was measured once per week. The cardiac ultrasound was performed 4 weeks later. Rats were killed and then blood was sampled from abdominal aorta. mRNA expressions of liver PPARgamma and angiotensin II type 1 receptor (AT1R) were detected by fluorescence real-time quantitative PCR. Protein expressions of PPARgamma and AT1R were detected using immunohistochemical assay (SP). The contents of PPARgamma and AT1R were quantitatively analyzed by Western blot.</p><p><b>RESULTS</b>After 4 weeks of treatment, the blood pressure decreased in the CM group, showing statistical difference when compared with the blank control group (P < 0.01). CM was inferior to WM in lowering blood pressure. But as a whole, CM was more stable and could maintain blood pressure at a relatively stable level. The cardiac ejection fraction increased in the CM group, showing statistical difference when compared with the blank control group (P < 0.05, P < 0.01). The mRNA and protein expressions of liver PPARgamma were up-regulated in the CM group, showing statistical difference when compared with the blank control group (P < 0.05, P < 0.01). CM could obviously inhibit the AT1R mRNA expression, and down-regulate the protein expression of AT1R, showing statistical difference when compared with the blank control group and the WM group respectively (P < 0.01).</p><p><b>CONCLUSION</b>SXC decreased blood pressure and improved the cardiac ejection fraction, which might be partially achieved by up-regulating the PPARgamma mRNA expression and protein synthesis, and inhibiting the AT1R mRNA expression and AT1R protein synthesis.</p>

Feasibility and safety of CT-guided percutaneous needle biopsy and subsequent iodine-125 seed interstitial implantation for pancreatic cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To discuss the feasibility and safety of different approaches for CT-guided percutaneous needle biopsy and subsequent iodine-125 seed interstitial implantation for pancreatic cancer.</p><p><b>METHODS</b>A retrospective study was carried out on the complete data of 35 patients with pancreatic cancer who have received CT-guided percutaneous needle biopsy with or without subsequent iodine-125 seed interstitial implantation. There were 9 lesions located in the head of pancreas, 20 located in the body, and 6 in the tail. The maximum diameter of the lesions varied from 12 mm to 60 mm (mean 37.1 mm). The patients were treated with a needle in diameter of 16-21G. Operations were undertaken via anterior, posterior and lateral approaches.</p><p><b>RESULTS</b>Thirty-five patients underwent 43 times of CT-guided percutaneous needle biopsies. Thirty-one cases were pathologically diagnosed as cancer, 2 cases inflammatory lesions, and 2 were suspected tumors (one of which was finally diagnosed as cancer, while another was pancreatic pseudocyst). The ratio of correct diagnosis was 94.3%. Fourteen patients were treated subsequently with CT-guided iodine-125 seed interstitial implantation therapy, with a total of 65 times of needle puncture. The operations were performed via direct approach to the tumor in 18 cases, transhepatic approach in 2 cases, transgastric approach in 4 cases, transintestinal approach in 10 cases, and through mesenteric vessels in one case. Incidence of complications in the biopsy group was 2.32% (1/43), and in the implantation group was 6.15% (4/65), with a statistically non-significant difference (P = 0.600) between the two groups. Incidence of complications in the group using 16-18G needle was 4.65% (4/86), while in the group using 20-21G needle was 4.55% (1/22), also with a non-significant difference (P = 0.064). The accuracy rate of needle biopsy in this study was 94.28% (33/35).</p><p><b>CONCLUSION</b>CT-guided percutaneous needle biopsy and subsequent iodine-125 seed interstitial implantation are both feasible and safe for pancreatic cancer.</p>

Anatomical and biomechanical analysis of sacral pedicle and lateral mass / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To study the anatomical and biomechanical features of sacral pedicle and lateral mass so as to provide reference for clinical screw fixation technology of sacral pedicle and lateral mass.</p><p><b>METHODS</b>A total of 60 adult patients'spiral CT images of the sacrum and coccyx were selected randomly. The entry points of sacral pedicle and lateral mass screws were determined, and the screw trajectory was measured using the three dimensional reconstruction method. Meanwhile, the gross anatomy was scrutinized in 15 adult cadaver specimens to determine the sacral pedicle and lateral mass screw entry points. The length, width and angle of sacral pedicle and lateral mass screw trajectory were measured. Eight of 15 cadaver specimens were selected to test the maximal extraction force of sacral pedicle and lateral mass screws. The clinical data of 15 cases treated by pedicle and lateral mass screw technology were collected and analyzed.</p><p><b>RESULTS</b>The diameter and length of S(1)-S(5) sacral pedicle and lateral mass screw trajectory were regular, with about 20 degree inclination angle. The S(1) pedicle screw entry point was located at the intersection point of the basal lateral part of articular process and median line of transverse process, and no significant difference was found for the maximal extraction force between pedicle and lateral mass screws (P larger than 0.05). The entry points of S(2)-S(5) pedicle screws were located at the intersection point of the line connecting adjacent posterior sacral foramina and median line of the transverse process. The lateral mass screw entry point of S(2)-S(5) was on the median side of intersection point between median line of the transverse process and lateral sacral crest. The maximal extraction force of pedicle screws was significantly greater than that of lateral mass screws (P less than 0.05).</p><p><b>CONCLUSION</b>Both the sacral pedicle and the lateral mass screw fixation techniques can offer effective fixation and reconstruction for fracture of the sacrum and coccyx, but pedicle screw fixation may be more convenient, safe and reliable than lateral mass screw fixation.</p>

Anatomical and Biomechanical Study of Sacral Pedicle and Lateral Mass / 医用生物力学

Objective To study the anatomical and biomechanical features of sacral pedicle and lateral mass to provide evidence for clinical sacral pedicle and lateral mass screw fixation technology. Method 60 adult patient's spiral CT images of sacrum and coccyx were selected randomly. The sacral pedicle and lateral mass screw entry point was determined, and the crew trajectory were measured using the three dimensional reconstruction. Meanwhile, the gross anatomy was done for 15 adult cadavers to determine the sacral pedicle and lateral mass screw entry point. The length, width and angle of sacral pedicle and lateral mass screw trajectory was measured. 8 of 15 cadaver specimens were selected to test for the maximal extraction force for sacral pedicle and lateral mass screws. ResultsThe diameter and length of S1～S5 sacral pedicle and lateral mass screw trajectory are significantly regular, with inclination angle is about 20°. The S1 pedicle screw entry point is located at intersection point of basal lateral part of articular process and median line of transverse process, no significant difference is found between the maximal extraction force of pedicle and lateral mass screws (P>0.05）. The entry points of S2～5 pedicle screws are located at the intersection point of the line connecting adjacent posterior sacral foramina and median line of transverse process. The lateral mass screw entry point of S2～5 is on the median side of intersection point between median line of transverse process and lateral sacral crest. The maximal extraction force of pedicle screws are significantly different from the lateral mass screws（P<0.05）. Conclusions Both the sacral pedicle and the lateral mass screw fixation technology can offer effective fixation and reconstruction for the fracture of sacrum and coccyx, but the pedicle screw fixation may be more convenient, safe and reliable than the lateral mass screw fixation technology.