Objective To investigate the impact of mitophagy,mediated by the long non-coding RNA SNHG16(LncRNA SNHG16)on diabetes-associated cognitive impairment(DCI).Methods 29 male C57BL/J mice were randomly divided into normal control(NC)group,DCI group and DCI+mitochondrial autophagy inhibitor(DCI+Mdivi-1)group.Morris water maze and new object recognition test were used to detect the cognitive function of mice,qRT-CPR was used to detect the expression of LncRNA SNHG16 and mitochondrial autophagy marker mRNA.Western blot were used to detect the expression of related protein.The mouse hippocampal neurons HT22 were divided into control(Con)group,high glucose(HG)group,HG+SNHG16 silencing(HG+sh-SNHG16)group and HG+no-load control(HG+sh-NC)group.CCK8 method and lactate dehydrogenase(LDH)method were used to detect neuronal damage.JC-1 method was used to detect mitochondrial membrane potential.Results Compared with NC group,the expression of LncRNA SNHG16 and the expression of autophagy-related gene 5,PTEN-induced putative kinase 1(PINK1),Parkin and microtubule associated protein light chain 3(LC3)Ⅱ/Ⅰ increased(P<0.05),while the expression of mitochondrial autophagy-related proteins P62 and mitochondrial outer membrane transposase 20(TOMM20)decreased in T2DM group.Compared with DCI group,the cognitive dysfunction of mice improved,and the expression level of LncRNA SNHG16 decreased in the DCI+Mdivi-1 group(P<0.05).The expressions of LncRNA SNHG16,LC3 Ⅱ/Ⅰ,PINK1 and Parkin were higher in HG group than in Con group(P<0.05),while the cell survival rate and TOMM20 protein expression were lower in HG group than in Con group(P<0.05).Silence of LncRNA SNHG16 can restore the activity of HT22 cells and mitochondrial membrane potential,and reduce the level of mitochondrial autophagy under HG condition.Conclusions The expression level of LncRNA SNHG16 was up-regulated in the hippocampus brain region of mice with diabetic cognitive dysfunction,and mitophagy was overactivated.Silencing of LncRNA SNHG16 inhibits mitophagy in hippocampal neurons and alleviates HG induced hippocampal neuronal damage.

Objective To investigate the impact of mitophagy,mediated by the long non-coding RNA SNHG16(LncRNA SNHG16)on diabetes-associated cognitive impairment(DCI).Methods 29 male C57BL/J mice were randomly divided into normal control(NC)group,DCI group and DCI+mitochondrial autophagy inhibitor(DCI+Mdivi-1)group.Morris water maze and new object recognition test were used to detect the cognitive function of mice,qRT-CPR was used to detect the expression of LncRNA SNHG16 and mitochondrial autophagy marker mRNA.Western blot were used to detect the expression of related protein.The mouse hippocampal neurons HT22 were divided into control(Con)group,high glucose(HG)group,HG+SNHG16 silencing(HG+sh-SNHG16)group and HG+no-load control(HG+sh-NC)group.CCK8 method and lactate dehydrogenase(LDH)method were used to detect neuronal damage.JC-1 method was used to detect mitochondrial membrane potential.Results Compared with NC group,the expression of LncRNA SNHG16 and the expression of autophagy-related gene 5,PTEN-induced putative kinase 1(PINK1),Parkin and microtubule associated protein light chain 3(LC3)Ⅱ/Ⅰ increased(P<0.05),while the expression of mitochondrial autophagy-related proteins P62 and mitochondrial outer membrane transposase 20(TOMM20)decreased in T2DM group.Compared with DCI group,the cognitive dysfunction of mice improved,and the expression level of LncRNA SNHG16 decreased in the DCI+Mdivi-1 group(P<0.05).The expressions of LncRNA SNHG16,LC3 Ⅱ/Ⅰ,PINK1 and Parkin were higher in HG group than in Con group(P<0.05),while the cell survival rate and TOMM20 protein expression were lower in HG group than in Con group(P<0.05).Silence of LncRNA SNHG16 can restore the activity of HT22 cells and mitochondrial membrane potential,and reduce the level of mitochondrial autophagy under HG condition.Conclusions The expression level of LncRNA SNHG16 was up-regulated in the hippocampus brain region of mice with diabetic cognitive dysfunction,and mitophagy was overactivated.Silencing of LncRNA SNHG16 inhibits mitophagy in hippocampal neurons and alleviates HG induced hippocampal neuronal damage.

Objective To investigate the characteristics of knee kinematics and ground reaction force (GRF), as well as the stress state of cartilage and meniscus in the process of lateral incisions at different cutting angles under expected conditions. Methods Kinematics and GRF data of 14 subjects at 45°, 90° and 135° cutting angle respectively under expected conditions were collected. The knee joint reaction force was obtained through the inverse dynamics calculation of Visual 3D. Based on three-dimensional (3D) finite element model of the knee joint, the contact process at 3 lateral cutting angles was simulated. ResultsUnder expected conditions, there were significant differences in knee joint kinematics characteristics at 3 cutting angles during contact process(P＜0.001), and the knee flexion increased with the cutting angle increasing; the vertical GRF decreased significantly with the cutting angle increasing (P＜0.001), while the horizontal GRF showed the opposite trend; for 3 cutting angles, the peak contact stress of patellar cartilage and femoral cartilage was larger at 90° cutting angle, the peak principal stress at anterior cruciate ligament (ACL) contact point was also larger at 90° cutting angle, and the following was at 135° and 45° cutting angle, respectively; the peak contact stress of lateral femoral cartilage was larger than that of medial femoral cartilage at 3 cutting angles. Conclusions The risk of knee joint injury is higher at 90° cutting angle, and the stress state of knee joint at 135° cutting angles is better than that at 90° cutting angle, and the risk of knee joint injury does not increase with the increase of cutting angle under expected conditions.

Objective: To describe the status of cognition about colorectal cancer and the screening and its relevant factors among first degree relatives of hereditary colorectal cancer patients in Guangzhou. Methods: Totally 274 subjects were investigated by a self-designed demographic questionnaire and the Chinese version of Cognitive Questionnaire for Colorectal Cancer and were analyzed by chisquare test, rank sum test and logistic regressive. Results: 60.2% (165/274) cases had a high level of cognition about colorectal cancer, 23.7% (65/274) had middle level of cognition about colorectal cancer and 16.0% (44/274) had a low level of cognition about colorectal cancer. Multivariate logistic regression analysis showed that age, sex, degree of education, marital status, family income, medical insurance and the number of cancer patients in his family were related factors (P<0.05). People who were young, female, highly educated, high family income, single, public/urban health insurance, commercial insurance and with more than 4 relatives suffering from colorectal cancer have higher cognitive level. Conclusions The level of cognition about colorectal cancer among first degree relatives of hereditary colorectal cancer patients was a little high. Medical staff should pay attention to relevant factors of health belief in subjects and develop targeted intervention to improve the level of cognition among these subjects and to promote their screening behavior.

OBJECTIVE: To evaluate the capacity and efficiency of human umbilical cord mesenchymal stem cells (HUCMSCs) to differentiate into neuron- like cells after induction with B27- supplemented serum- free medium. METHODS: HUCMSCs at passage 4 were cultured for 14 days with serum-containing medium (SCM) (group A), SCM supplemented with 20 ng/mL nerve growth factor (NGF) and 10 ng/mL basic fibroblast growth factor (bFGF) (group B), serum-free medium (SFM) (group C), or SFM supplemented with 20 ng/mL NGF and 10 ng/mL bFGF. The culture medium were changed every 3 days and the growth of the neurospheres was observed using an inverted microscope. The cell markers were analyzed with flow cytometry and the expressions of nestin, neuron- specific enolase (NSE), neurofilament heavy polypeptide (NEFH), and glial fibrillary acidic protein (GFAP) were quantified by quantitative real-time PCR (qRT-PCR) and Western blotting. RESULTS: Before induction, HUCMSCs expressed abundant mesenchymal stem cell surface markers including CD29 (99.5%), CD44 (49.6%) and CD105 (77.7%). Neuron-like cells were observed in the cultures on days 7, 10, and 14, and the cell differentiation was the best in group D, followed by groups C, B and A. In all the 4 groups, the cellular expressions of nestin and GFAP gradually lowered while those of NEFH and NSE increased progressively. The expressions of GFAP, NEFH, nestin and NSE were significantly different between group A and the other 3 groups ( < 0.001 or 0.05). CONCLUSIONS B27-supplemented SFM effectively induces the differentiation of HUCMSCs into neuron- like cells, and the supplementation with cytokines (NGF and bFGF) strongly promotes the cell differentiation.

Surgical resection is the best method for patients with colorectal cancer liver metastases. However, tumor recurrence rate is still high after surgery. Preoperative chemotherapy can help shrink the tumor, test biological behavior, and reduce recurrence rate; but it may also cause liver injury and delay surgery. There is still controversy whether neoadjuvant chemotherapy should be performed and how to select patients from chemotherapy before surgery. Thus, in this article, combined the research progress and the clinical experience of author's center, we discuss this issue in 4 aspects: the development of neoadjuvant chemotherapy; the indications and guideline recommendation for neoadjuvant chemotherapy; the selection of neoadjuvant chemotherapy regimens; common problems in neoadjuvant chemotherapy.

Objective:To compare long-term efficacy between watch and wait (W&W) strategy and total mesorectal excision (TME) in patients who were diagnosed with locally advanced rectal cancer (LARC) and attained clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT).Methods:A retrospective cohort study was carried out. A total of 238 patients with stage II-III LARC exhibiting cCR after nCRT in Sun Yat-sen University Cancer Center from September 16, 2010 to January 9, 2018 were enrolled. Patients who were diagnosed with other malignant tumor within 5 years, did not receive regular follow-up in our center for more than 1 year and had no complete examination items after nCRT were excluded. Of 238 patients, 151 were male and 87 were female with a median age of 57 (27-83) years old. According to TNM stage, 61 cases were cII, 177 cases were cIII. Concurrent chemoradiotherapy (CCRT) was performed in 20 patients. CCRT plus induction/consolidated chemotherapy was performed in 218 patients. Intensity-modulated radiotherapy (IMRT) was applied to radiotherapy. The median radiation dose was 50 Gy/25 Fr for both the primary tumor and clinical target volumes, and the total dose was 45.0 to 50.6 Gy for 227 patients. In 27 patients, single-agent fluorouracil or capecitabine was used as concurrent chemotherapy. But in the other 211 patients, a combined regimen of oxaliplatin and fluorouracil or capecitabine was used. After nCRT, 59 and 179 patients received W&W (W&W group) and TME 6-12 weeks later (TME group), respectively. After the ending of treatment, patient was interviewed one time every 3 months and after 3 years, one time every six months. Overall survival (OS) rate, distant-metastasis-free survival (DMFS) rate, and local-recurrence-free survival (LRFS) rate were compared between two groups. The salvage treatment and sphincter preservation rate were analyzed. The survival curve was drawn with Kaplan-Meier method and evaluated by log-rank method.Results:In the cases treated with TME, the median interval from nCRT to surgery was 59 days. The postoperative pCR rate was 63.1%(113/179). The median follow-up time of the whole cohort was 41.8 (12.0-99.0) months. The 3-year and 5-year OS rates were 98.4% and 96.5%; the 3-year and 5-year LRFS rates were 96.5% and 96.5%; the 3- and 5-year DMFS rates were 91.0% and 87.9%, respectively. The 3-year OS rates in the W&W group and the TME group were 100% and 97.9%; the 5-year OS rates in W&W group and the TME group were 90.6% and 97.9% ( P=0.339); The 3-year local recurrence rate (LRR) in the W&W group was 12.9% (7 cases recurred within 2 years), which was significanthy higher then that in the TME group (0.6%, P=0.003). Salvage surgery was successful in 5/6 cases. After salvage surgery, LRFS rate was not significantly different between the two groups ( P=0.137). The 3-year DMFS rate in the W&W group and the TME group were 88.4% and 81.1%, whose difference was not significant ( P=0.593). Recurrence with simultaneous metastasis was seen in 3/7 cases of the W&W group. The sphincter was preserved in 89.8% (53/59) of patients in the W&W group, which was significantly higher than 73.7% (132/179) in the TME group ( P<0.001). When distance of tumor from the anal verge was ≤ 5 cm, the sphincter preservation rate (SPR) in the W&W group was 88.0% (44/50), which was significantly higher than the 54.4% (56/103) in the TME group ( P<0.001). Conclusions:W&W is safe and feasible for patients with LARC and cCR after nCRT. The results should be verified by further clinical trials.

Objective:To compare long-term efficacy between watch and wait (W&W) strategy and total mesorectal excision (TME) in patients who were diagnosed with locally advanced rectal cancer (LARC) and attained clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT).Methods:A retrospective cohort study was carried out. A total of 238 patients with stage II-III LARC exhibiting cCR after nCRT in Sun Yat-sen University Cancer Center from September 16, 2010 to January 9, 2018 were enrolled. Patients who were diagnosed with other malignant tumor within 5 years, did not receive regular follow-up in our center for more than 1 year and had no complete examination items after nCRT were excluded. Of 238 patients, 151 were male and 87 were female with a median age of 57 (27-83) years old. According to TNM stage, 61 cases were cII, 177 cases were cIII. Concurrent chemoradiotherapy (CCRT) was performed in 20 patients. CCRT plus induction/consolidated chemotherapy was performed in 218 patients. Intensity-modulated radiotherapy (IMRT) was applied to radiotherapy. The median radiation dose was 50 Gy/25 Fr for both the primary tumor and clinical target volumes, and the total dose was 45.0 to 50.6 Gy for 227 patients. In 27 patients, single-agent fluorouracil or capecitabine was used as concurrent chemotherapy. But in the other 211 patients, a combined regimen of oxaliplatin and fluorouracil or capecitabine was used. After nCRT, 59 and 179 patients received W&W (W&W group) and TME 6-12 weeks later (TME group), respectively. After the ending of treatment, patient was interviewed one time every 3 months and after 3 years, one time every six months. Overall survival (OS) rate, distant-metastasis-free survival (DMFS) rate, and local-recurrence-free survival (LRFS) rate were compared between two groups. The salvage treatment and sphincter preservation rate were analyzed. The survival curve was drawn with Kaplan-Meier method and evaluated by log-rank method.Results:In the cases treated with TME, the median interval from nCRT to surgery was 59 days. The postoperative pCR rate was 63.1%(113/179). The median follow-up time of the whole cohort was 41.8 (12.0-99.0) months. The 3-year and 5-year OS rates were 98.4% and 96.5%; the 3-year and 5-year LRFS rates were 96.5% and 96.5%; the 3- and 5-year DMFS rates were 91.0% and 87.9%, respectively. The 3-year OS rates in the W&W group and the TME group were 100% and 97.9%; the 5-year OS rates in W&W group and the TME group were 90.6% and 97.9% ( P=0.339); The 3-year local recurrence rate (LRR) in the W&W group was 12.9% (7 cases recurred within 2 years), which was significanthy higher then that in the TME group (0.6%, P=0.003). Salvage surgery was successful in 5/6 cases. After salvage surgery, LRFS rate was not significantly different between the two groups ( P=0.137). The 3-year DMFS rate in the W&W group and the TME group were 88.4% and 81.1%, whose difference was not significant ( P=0.593). Recurrence with simultaneous metastasis was seen in 3/7 cases of the W&W group. The sphincter was preserved in 89.8% (53/59) of patients in the W&W group, which was significantly higher than 73.7% (132/179) in the TME group ( P<0.001). When distance of tumor from the anal verge was ≤ 5 cm, the sphincter preservation rate (SPR) in the W&W group was 88.0% (44/50), which was significantly higher than the 54.4% (56/103) in the TME group ( P<0.001). Conclusions:W&W is safe and feasible for patients with LARC and cCR after nCRT. The results should be verified by further clinical trials.

OBJECTIVE: To investigate the evaluation value of preoperative peripheral blood lymphocyte-to-monocyte ratio (LMR) on the prognosis of patients with stage III colon cancer undergoing radical resection and postoperative adjuvant chemotherapy. METHODS: Electronic medical record were retrospectively retrived for stage III colon cancer patients who underwent radical surgery at Sun Yat-sen University Cancer Center from December 2007 to December 2013. Inclusion criteria were pathologically comfirmed colon adenocarcinoma, complete clinicopathological data, and postoperative XELOX (oxaliplatin + capecitabine) chemotherapy with follow-up of at least 3 months. Patients with neoadjuvant anti-tumor therapy, infectious disease, other malignant tumors and death of non-tumor causes within 3 months after operation were excluded. A total of 258 patients were included in this retrospective cohort study, including 146 males and 112 females with median age of 55 (22 to 85) years. Tumors of 100(38.8%) patients were located in the right hemicolon, and of 158 (61.2%) in the left hemicolon. Tumors of 194(75.2%) patients were highly and moderately differentiated, and of 64 (24.8%) were poorly differentiated. According to the TNM tumor pathological stage of AJCC 7th edition, 196 (76.0%) patients were stage IIIA to IIIB, and 62(24.0%) patients were stage IIIC. The median preoperative CEA was 3.8 (0.3 to 287.5) μg /L and the median cycle of the adjuvant chemotherapy was 6 (1 to 8). The cut-off value of preoperative LMR in prediction of 3-year overall survival (OS) outcome was determined by receiver operating characteristic (ROC) curve analysis. All patients were divided into low LMR group and high LMR group according to the critical value. Clinicopathological characteristics between the two groups were compared by using chi-square test or Fisher's exact test as appropriate. The 3-year disease-free survival and overall survival rate were estimated with the Kaplan-Meier method, and differences between two groups were assessed with the log-rank test. Univariate and multivariate analyses were performed through Cox regression model. RESULTS: ROC curve showed that the cut-off value of preoperative LMR in predicting 3-year overall survival was 4.29. Then 143 patients were divided into low LMR group (LMR<4.29) and 115 patients into high LMR group (LMR ≥ 4.29). Compared with high LMR group, the low LMR group presented higher proportions of male [62.2%(89/143) vs. 50.4%(58/115), χ²=4.167, P=0.041], right hemicolon cancer [44.8% (64/143) vs. 31.3% (36/115), χ²=4.858, P=0.028], and the largest tumor diameter>4 cm [60.1% (86/143) vs. 33.0% (38/115), χ²=18.748, P<0.001]. During a median follow-up of 46.0 (range, 3.0 to 74.0) months, 3-year disease-free survival rate was 83.8% in high LMR group and 78.9% in low LMR group, which was not significantly different (P=0.210). While 3-year overall survival rate in low LMR group was significant lower than that in high LMR group (86.6% vs. 97.2%, P=0.018). Univariate analysis revealed that preoperative low LMR (HR=2.841, 95%CI: 1.146 to 7.043, P=0.024), right hemicolon cancer (HR=2.865, 95%CI: 1.312 to 6.258, P=0.008) and postoperative adjuvant chemotherapy≥6 cycles (HR=0.420, 95%CI: 0.188 to 0.935, P=0.034) were the risk factors for poor overall survival. Multivariate analysis identified that preoperative low LMR (HR=2.550, 95%CI: 1.024 to 6.347, P=0.004) and right hemicolon cancer (HR=2.611, 95%CI: 1.191 to 5.723, P=0.017) were the independent risk factors for overall survival. CONCLUSIONS Preoperative peripheral blood LMR level represents an effective prognostic predictor for patients with stage III colon cancer receiving radical therapy. Low LMR indicates the poor prognosis and such patients require aggressive postoperative treatment strategy.
Adenocarcinoma ; blood ; drug therapy ; surgery ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Chemotherapy, Adjuvant ; Colonic Neoplasms ; blood ; drug therapy ; surgery ; therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Leukocyte Count ; methods ; Lymphocytes ; Male ; Middle Aged ; Monocytes ; Preoperative Care ; Prognosis ; Retrospective Studies ; Young Adult

Objective To explore the application of 3D printing templates for titanium plate contouring (TrPC) in pelvic ring surgery.Methods From May 2016 to June 2018,12 patients with pelvic ring injury were treated by internal fixation with 24 titanium plates at Department of Orthopedics and Trauma,Sanshui People's Hospital.After solid digital models of the damaged pelves of the patients were reconstructed from their CT images via software,the hollowed ones were created with the wall thickness of 1.2 mm.After the models of damaged pelves were restored to be intact,the templates for titanium plate contouring were designed based on the area of fixation and manufactured via a stereo lithography apparatus.The total manufacturing time and material consumption of 3D printing TTPC were recorded and compared with those of 3D printing solid and hollow models.Before operation,the titanium plates were contoured according to the templates.The time for preoperative shaping the plate and the time for intraoperative preparing the plate before installation were recorded.After operation,all patients underwent CT scan again for reconstruction of 3D models of the postoperative pelves which were compared with their corresponding preoperative ones in the software.Matta criteria were used to evaluate the pelvic reduction and Majeed criteria to evaluate the functional recovery 6 months after operation.Results All patients were followed up for 6 to 28 months (average,16.3 months).The total manufacturing time and material consumption of 3D printing a TTPC were significantly less than those of 3D printing a solid or hollow model (P ＜ 0.05).The time for preoperative shaping the plate was 12.8 ± 4.1 minutes and the time for intraoperative preparing the plate was 1.4 ± 1.1 minutes.The average deviation between the preoperative 3D models and the postoperative ones was 1.4 ± 1.1 mm.According to the Matta criteria for pelvic reduction,6 cases were excellent,4 good and 2 satisfactory.According to the Majeed criteria,the pelvic functions were excellent in 7 cases,good in 4,and fair in one.Conclusion Application of 3D printing TTPC in the surgery for pelvic ring injury is advantageous in lowering the costs of 3D printing and reducing the intraoperative time for contouring the titanium plate,leading to satisfactory outcomes.