AIM:To investigate whether oxidative stress is able to induce autophagy in mesenchymal stem cells (MSCs), and to explore the effects of autophagy on MSC proliferation and apoptosis under oxidative stress circumstance as well as the underlying mechanism for promoting the therapeutic effects of transplanted MSCs on treating diabetes mellitus e -rectile dysfunction ( DMED) .METHODS: Hydrogen peroxide ( H2 O2 ) was applied to simulate the oxidative stress cir-cumstance.The effects of H2 O2 at concentration of 0, 50, 100, 200, 400μmol/L on the viability of MSCs were tested by the method of Trypan blue exclusion and MTT assay respectively .The methods of MTT assay , Western blot and transmis-sion electron microscope ( TEM) were used to explore the effects of H 2 O2 on MSC apoptosis and autophagy .RESULTS:The proliferation of MSCs was obviously inhibited by H 2 O2 in a dose-dependent manner ( P<0.01) and the 50%inhibiting concentration (IC50) was (384.58 ±16.89) μmol/L.H2O2 induced apoptosis and autophay of MSCs .The proliferation rate of MSCs was suppressed by H 2 O2 significantly ( P<0.05 ) , with a further decline by blockade of autophagy ( P<0.05) whereas increased by blockade of apoptosis (P<0.05).H2O2 induced MSCs apoptosis obviously (P<0.05), with an augment of apoptosis ( P<0.05) by blockade of autophagy .Furthermore, the H2 O2 increased expression of cleaved caspase-3 and cleavage of poly ADP-ribose polymerase 1 (PARP1), Which were decreased by apoptosis blockade whereas were enhanced by blockade of autopahgy .CONCLUSION:Oxidative stress plays a dual role in MSC survival , which in-duces MSC apoptosis and autophagy .Moreover , blockade of autophagy intensifies MSC apoptosis .Therefore , it is a promis-ing method to ameliorate the effects of stem-cell based therapy on DMED by enhancing protective autophagy to increase the survival rate of transplanted MSCs against oxidative stress circumstance caused by diabetes mellitus .

Objective To analyze the histological changes of bone diseases and to investigate the noninvasive measurements for diagnosing renal osteodystrophy (ROD) in maintenance dialysis patients . Methods Ninety-one patients were selected to receive bone biopsy . The bone samples were stained with HE, toluidine blue and Masson, and were examined with light microscopy . The levels of immunoreactive parathyroid hormone (iPTH), osteoprotegerin (OPG),sRANKL and osteocalcin (OCN) were determined in the patients enrolled from 2004 to 2006 . The level of iPTH was measured by radioimmunoassay . OPG and sRANKL were measured by ELISA,and OCN was measured by chemiluminescence . Results The incidence of ROD in the maintenance patients was 100% . According to the histological appearance, 50 cases (54 .9%) were high turnover bone disease (secondary hyperparathyroid bone disease), 9 cases (9 .9%) were low turnover bone diseases(osteomalacia and adynamic bone disease), and 32 cases(35 .2% ) were mixed bone disease . The level of iPTH in patients with ROD was significantly increased compared with healthy controls . It was the lowest in low turnover bone diseases . There was no difference among three types of ROD . OPG level was significantly increased compared with healthy controls [(2176 .58±1576 .08) pmol/L vs (1310 .46±1254 .00) pmol/L, P＜0 .05] . The level in high turnover bone diseases was higher than that of the healthy controls [(2261 .85±1712 .22) pmol/L vs (1310 .46±1254 .00) pmol/L, P＜0 .05] . There was no difference among three types of ROD .sRANKL level in high turnover bone disease was significantly increased compared with healthy controls [(0 .328±0 .524)pmol/L vs (0 .084±0 .190) pmol/L, P＜0 .05] . OCN level was also higher than that of the healthy controls (P＜0 .05), and the OCN level in low turnover ROD was the lowest among three types of ROD . OCN level in mixed ROD was dramatically increased as compared to low turnover ROD [(226 .633±66 .455) pmol/L vs (193 .03±104 .269) pmol/L, P ＜0 .05] .Conclusions The histological changes of bone disease can be indicated by iPTH level, but the types of ROD can not be distinguished according to iPTH level neither be differentiated by the levels of OPG, sRANKL and OCN . Bone histomorphometry is still the golden standard for diagnosing renal osteodystrophy .

Objective To investigate the clinical features of VAE and to assess the predictive value of VAE cough. Methods We retrospectively reviewed the medical records of 461 consecutive patients who underwent DBS surgery at Beijing Tiantan Hospital. Patients with VAE manifestation were enrolled in this study. The clinical features, operative courses, post-operative conditions and treatment of these patients were analyzed. The correlation between intraoperative tremor intensity , cough duration and prognosis was also investigated. Results Among 461 patients,10 (2.2%) were found with evidence of VAE, including cough, dyspnea, decreased O2 saturation (SO2). Statistical analyses revealed that severe cough was associated with greater age , a longer coughing time, more intensive tremor, greater influence, and a longer length of stay (P < 0.05, rspectively). Conclusions Early recognition and prompt management of VAE are essential to prevent unfavorable consequences. Cough intensity might be a useful tool for evaluating VAE and its prognosis , which is helpful for neurosurgeons to decide on the subsequent maneuvers.

Since the establishment of eight-year clinical medicine specialty, in line with the princi-ple of "eight-year consistency and fusion of the bachelor and doctor degree", the training mode of "strength-ening the foundation, focusing on quality, overall optimization, facing the clinical" has been implemented. In order to reach the standard of professional doctorate, a series of courses of professional doctorate need to be fused in limited time and designed carefully by medical schools. However, grasping proper teaching time and opportunity is particularly important for students' learning and development. By collecting the courses information of 11 medical colleges and universities offering eight-year clinical medicine specialty, we have analyzed the teaching time, methods and course categories of scientific research training courses and graduate degree courses, aiming to find the appropriate teaching program.

Objective To investigate the incidence rate, pathologic changes, mechanisms and diagnostic methods in renal bone disease.Methods The blood levels of carboxyterminal parpthyriod hormone (C-PTH), 1,25(OH)2D3, calcium and phosphate, aluminum in serum and bone tissue were measured. The bone biopsy and bone scan with 99m technetium methylene diphosphonate (99m TC-MDP) were performed in 51 uremic patients.Results One hundred per cent of the patients had varying degree of pathologic changes in bone, in which 50.9% of the patients presented high-turnover bone disease, 7.8% of the patients presented lowe-turnover bone disease and 41.8% of the patients had mixed-type bone disease. The levels of serum C-PTH were predominently high in high-turnover bone disease while the levels of serum 1,25(OH)2D3 were significantly decreased in low-turnover bone disease. There was a high positive rate for the diagnosis of renal bone disease by bone scan with 99m TC-MDP.Conclusions The examination of bone pathology is the most valuable method for the diagnosis of renal bone disease. Bone scan with 99m TC-MDP has reference value when clinical conditions do not allow to make bone biopsy.

Objective To investigate the influences of anterior thalamic nucleus (ANT) stimulation on neurogenesis in hippocampus of epileptic rats. Methods Thirty-two male SD rats were randomly alloca-ted to normal-control group ( n＝8),control-stimulation group ( n＝8),sham-stimulation group ( n＝8) and model-stimulation group(n＝8).Eqileptic SD rat model was established by using microinjection of kainic acid in hippocampal CA3 area,and administered 48 h continuous ANT stimulation in the chronic stage.Epileptic seizures were monitored and counted.The levels of Ki-67,a neurogenesis protein in hippocampus was deter-mined by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Results The epi-lepsy seizure rate was (5.9±2.2) per week in the sham-stimulation group and (2.9±1.1) per week in model-stimulation group.Compared with sham-stimulated rats, ANT stimulation reduced seizures by 50.8%(P＜0.05).Western blot analysis revealed that the relative levels of Ki-67 in the hippocampus of model-stimula-tion group significantly higher than that of the sham-stimulation group((0.44±0.15) vs (0.19±0.73),P＜0.05).qRT-PCR analysis showed that relative levels of Ki-67 mRNA in the hippocampus of model-stimula-tion group were significantly higher than that of the sham-stimulation group((0.45±0.10) vs (0.15±0.06), P＜0.05). Conclusion Chronic ANT stimulation can promote neurogenesis in epileptic rats,which may be a principle mechanism of the beneficial effect of ANT stimulation on epilepsy.

Objective:This study aims to analyze the prognosis of patients who underwent a simultaneous operations for colorectal cancer and liver metastases, and to establish a prognostic scoring system for these patients.Methods:From January 2010 to March 2019, the clinicopathological data of patients with colorectal cancer and liver metastases simultaneously operated at Shanghai Changhai Hospital were collected. The clinicopathological prognostic factors on tumor recurrence and survival outcomes on follow-up were analyzed. Single and multiple factors Cox regression analyses were used to determine the risk factors which affected the prognosis of patients. Using the risk factors of poor prognosis on Cox analysis, 1 point was given to each risk factor. Patients were then divided into different groups according to the different total scores. The median overall survival and disease-free survival of each group were analyzed.Results:Of 234 patients included in this study, there were 126 males and 108 females. The average age was (57.4±10.8) years. The median survival was 44.85 months. The 1-, 3-, and 5-year survival rates of the whole group were 87.3%, 55.2%, and 22.9%, respectively. Primary tumor in right colon, preoperative carcinoembryonic antigen ≥200 ng/ml, multiple liver metastases, and poorly differentiated adenocarcinoma/mucinous adenocarcinoma were independent risk factors of poor prognosis. After 1 point was given to each of the above 4 items, patients were then divided into the low-risk (0-1) and high-risk (2-4) groups. The median survivals of patients in the low-risk group ( n=174) and high-risk group ( n=60) were 53 months and 29 months, respectively. The corresponding median disease-free survivals were 21.34 months and 8.48 months, respectively. The differences between the 2 groups were significant ( P<0.05). Conclusion:The results of this study preliminary established a predictive scoring system for patients with simultaneous colorectal cancer and liver which can play a role in selecting treatment options for these patients.

Objective:To investigate the clinical efficacy and prognosis of simultaneous resection of synchronous colorectal liver metastasis in patients admitted in different phases.Methods:The retrospective cohort study was conducted. The clinicopathological data of 346 patients who underwent simultaneous resection of synchronous colorectal liver metastasis in the First Affiliated Hospital of Naval Medical University (Changhai Hospital of Shanghai) from January 2000 to April 2021 were collected. There were 217 males and 129 females, aged (58±12)years. Patients under-went simultaneous resection of synchronous colorectal liver metastasis. Observation indicators: (1) clinicopathological features of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021; (2) surgical and postoperative situations of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021; (3) analysis of prognosis of patients with synchro-nous colorectal liver metastasis in 2000?2010 and 2011?2021. Follow-up was conducted using telephone interview or outpatient examination to detect survival of patients. The follow-up was performed once every 3 months, including blood routine test, liver and kidney function test, car-cinoembryonic antigen (CEA) test, CA19-9 test, abdominal B-ultrasound examination, and once every 6 months, including chest computed tomography (CT) plain scan, liver magnetic resonance imaging (MRI) and/or CT enhanced scan, abdominal or pelvic MRI and/or CT enhanced scan, within postoperative 2 year. The follow-up was performed once every 6?12 months within postoperative 2?5 years including above reexaminations. Electronic colonoscopy was performed once a year after operation. The follow-up was up to November 12, 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distuibution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-Rank test was used to conduct survival analysis. Results:(1) Clinicopathological features of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021. Of the 346 patients, 59 cases underwent simultaneous resection within 2000?2010 and 287 cases underwent simultaneous resection within 2011?2021. The gender (males and females), cases with or without fundamental diseases, cases with the number of lymph nodes harvested in primary lesion as <12 or ≥12, the tumor diameter of primary lesion, the tumor diameter of liver metastasis lesion, the number of liver metastasis lesions, cases with or without preoperative treatment, cases with or without postoperative treatment, cases with adjuvant therapy as perioperative treatment, surgery or other treatment were 47, 12, 36, 23, 19, 40, (5.5±2.4)cm, (2.1±0.7)cm, 1.6±0.5, 59, 0, 16, 16, 0, 16, 43 in patients admitted in 2000?2010, respectively. The above indicators in patients admitted in 2011?2021 were 170, 117, 121, 166, 58, 229, (4.2±2.0)cm, (3.0±2.0)cm, 1.9±1.4, 208, 79, 34, 235, 74, 29, 184, respectively. There were significant differences in the above indicators between patients admitted in 2000?2010 and 2011?2021 ( χ2=8.73, 7.02, 4.07, t= 4.40, ?6.04, ?3.10, χ2=21.05, 28.82, 26.68, P<0.05). (2) Surgical and postoperative situations of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021. Cases with surgical methods as complete open surgery or laparoscopy combined with open surgery, the operation time, time to postoperative initial liquid food intake, cases with or without postoperative complications, cases with postoperative duration of hospital stay as ≤10 days or >10 days were 58, 1, (281±57)minutes, (5±1)days, 33, 26, 14, 45 in patients admitted in 2000?2010, respec-tively. The above indicators in patients admitted in 2011?2021 were 140, 147, (261±82)minutes, (3±1)days, 233, 54, 198, 89, respectively. There were significant differences in the above indicators between patients admitted in 2000?2010 and 2011?2021 ( χ2=49.04, t=2.24, 7.53, χ2=17.56, 26.02, P<0.05). There was no death in the 346 patients. (3) Analysis of prognosis of patients with synchro-nous colorectal liver metastasis in 2000?2010 and 2011?2021. Of the 346 patients, 295 cases were followed up for 47(range, 1?108)months. Of the 29 patients admitted in 2000?2010 who were followed up, there were 27 cases died. The median survival time, 1-, 3-, 5-year overall survival rates, 1-, 3-, 5-year disease free survival rates of patients admitted in 2000?2010 were 18.0 months (95% confidence interval as 12.7?23.3 months), 82.8%, 11.5%, 3.8%, 53.6%, 8.3%, 4.2%, respec-tively. Of the 266 patients admitted in 2011?2021 who were followed up, there were 109 cases died. The median survival time, 1-, 3-, 5-year overall survival rates, 1-, 3-, 5-year disease free survival rates of patients admitted in 2011?2021 were 54.0 months (95% confidence interval as 38.1?70.4 months), 93.3%, 61.8%, 47.0%, 68.2%, 33.7%, 28.3%, respectively. There were significant differences in overall survival rate and disease free survival rate between patients admitted in 2000?2010 and 2011?2021 ( χ2=47.57, 9.17, P<0.05). Conclusions:With the increase of the operation volume of simultaneous resection of synchronous colorectal liver metastasis, the operation time, time to postoperative initial liquid food intake, postoperative duration of hospital stay and postoperative complications have significantly decreased, while the overall survival rate and disease free survival rate have significantly increased.

Objective To investigate the expression level of HNRNP A1 in colorectal cancer(CRC)and its prognostic implications.Methods We investigated HNRNP A1 expression level in CRC using HPA,TIMER,and GEPIA databases and analyzed its association with Ki-67 and VEGFA expressions.Kaplan-Meier Plotter database was used to analyze the correlation of HNRNP A1 mRNA levels with the survival rates of CRC patients.Pathway enrichment analysis was performed for predicting the biological roles of HNRNP A1 in CRC progression.Immunohistochemistry and Western blotting were used to examine the protein levels of HNRNP A1 in CRC versus adjacent tissues,and TIMER was used for assessing its expression in the infiltrating immune cells.In RKO/Caco2 cells,the effects of lentivirus-mediated knockdown of HNRNP A1 on cell proliferation and migration were observed,and the inhibitory effect of VPC-80051(a HNRNP A1 inhibitor)on cell proliferation was evaluated to assess its potential as a therapeutic agent.Results HNRNP A1 was significantly overexpressed in CRC tissues and correlated with a poor prognosis of the patients.HNRNP A1 expression level was correlated with the infiltrating immune cells in CRC microenvironment and positively correlated with MKI67 and VEGFA expressions in CRC.A high HNRNP A1 expression predicted a in survival and progression-free survival of CRC patients and was involved in multiple biological processes related with CRC progression.In RKO/Caco2 cells,HNRNP A1 knockdown significantly suppressed cell proliferation and migration,and treatment with VPC-80051 also effectively inhibited CRC cell proliferation.Immunohistochemical study demonstrated a close correlation of HNRNP A1 overexpression with tumor stage of CRC.Conclusion HNRNP A1 is overexpressed in CRC tissues to modulate cell proliferation and migration and is correlated with a poorer prognosis.VPC-80051 can effectively inhibit CRC cell proliferation,suggesting the potential of HNRNP A1 as a therapeutic target for CRC.

Objective To investigate the expression level of HNRNP A1 in colorectal cancer(CRC)and its prognostic implications.Methods We investigated HNRNP A1 expression level in CRC using HPA,TIMER,and GEPIA databases and analyzed its association with Ki-67 and VEGFA expressions.Kaplan-Meier Plotter database was used to analyze the correlation of HNRNP A1 mRNA levels with the survival rates of CRC patients.Pathway enrichment analysis was performed for predicting the biological roles of HNRNP A1 in CRC progression.Immunohistochemistry and Western blotting were used to examine the protein levels of HNRNP A1 in CRC versus adjacent tissues,and TIMER was used for assessing its expression in the infiltrating immune cells.In RKO/Caco2 cells,the effects of lentivirus-mediated knockdown of HNRNP A1 on cell proliferation and migration were observed,and the inhibitory effect of VPC-80051(a HNRNP A1 inhibitor)on cell proliferation was evaluated to assess its potential as a therapeutic agent.Results HNRNP A1 was significantly overexpressed in CRC tissues and correlated with a poor prognosis of the patients.HNRNP A1 expression level was correlated with the infiltrating immune cells in CRC microenvironment and positively correlated with MKI67 and VEGFA expressions in CRC.A high HNRNP A1 expression predicted a in survival and progression-free survival of CRC patients and was involved in multiple biological processes related with CRC progression.In RKO/Caco2 cells,HNRNP A1 knockdown significantly suppressed cell proliferation and migration,and treatment with VPC-80051 also effectively inhibited CRC cell proliferation.Immunohistochemical study demonstrated a close correlation of HNRNP A1 overexpression with tumor stage of CRC.Conclusion HNRNP A1 is overexpressed in CRC tissues to modulate cell proliferation and migration and is correlated with a poorer prognosis.VPC-80051 can effectively inhibit CRC cell proliferation,suggesting the potential of HNRNP A1 as a therapeutic target for CRC.