Multimodal prehabilitation before major abdominal surgery: A retrospective study

INTRODUCTION@#Prehabilitation may benefit older patients undergoing major surgeries. Currently, its efficacy has not been conclusively proven. This is a retrospective review of a multimodal prehabilitation programme.@*METHODS@#Patients aged 65 years and above undergoing major abdominal surgery between May 2015 and December 2019 in the National University Hospital were included in our institutional programme that incorporated aspects of multimodal prehabilitation and Enhanced Recovery After Surgery concepts as 1 holistic perioperative pathway to deal with issues specific to older patients. Physical therapy, nutritional advice and psychosocial support were provided as part of prehabilitation.@*RESULTS@#There were 335 patients in the prehabilitation cohort and 256 patients whose records were reviewed as control. No difference in postoperative length of stay (@*CONCLUSION@#The current study found no differences in traditional surgical outcome measures with and without prehabilitation. An increase in patient mobility in the immediate postoperative period was noted with prehabilitation, as well as an association between prehabilitation and increased adherence to postoperative adjuvant therapy. Larger prospective studies will be needed to validate the findings of this retrospective review.

Alterations in the transmural gradient of ventricular repolarization with different pacing sites in normal and heart failure canines / 生理学报

Alterations of the transmural gradient of repolarization may contribute to the increase of transmural dispersion of repolarization and ventricular arrhythmias. The transmural gradient of repolarization may play an important role in sudden death associated with left ventricular epicardial pacing. To investigate the changes of transmural gradient dispersion of ventricular repolarization with different pacing sites in heart failure (HF) canines, 8 mongrel dogs were randomized into healthy group and HF group (n = 4). We mapped the monophasic action potential duration (MAPD) in the subendocardial, subepicardial and mid-myocardial layers of the left ventricle (LV) in canines of healthy and HF groups during right atrium (RA) pacing, right ventricular apical endocardial (RV) pacing, left ventricular lateral epicardial (LV) pacing and biventricular (Biv) pacing respectively. The results showed that in the healthy group, the MAPDs were significantly different among the three layers during RA pacing (all P 0.05). In the HF group, the MAPDs in all three layers were prolonged compared with those in the same locations in the healthy group (all P 0.05). By MAP recording with our new mapping electrode, we found a transmural MAPD gradient among the three layers of the LV during RA pacing and the gradient between the subendocardial and subepicardial layers vanished during RV, LV or Biv pacing in healthy dogs. In contrast, there was no transmural MAPD gradient during RA, RV, LV or Biv pacing in HF dogs. These results are helpful to understand the mechanism of ventricular arrhythmias in patients with HF.

Effect of matrine on sensitivity of A549/DDP cells to cisplatin by inhibiting microRNA-192 / 中草药

Objective: To investigate the effect of matrine on increasing the sensitivity of A549/DDP cells to cisplatin by regulating microRNAs. Methods: Data mining was performed on a microarray dataset (accession ID: GSE43249) from GEO database using bioinformatics analysis. Then microRNAs which related to the sensitivity of A549 cells to cisplatin were selected as candidate microRNAs. A549 and A549/DDP cells were cultured in vitro. The expression changes of candidate microRNAs were confirmed by qRT-PCR. The effect of matrine on the level of candidate microRNAs was also determined by qRT-PCR in A549/DDP cells. The level of microRNA-192 (miR-192) in A549/DDP cells was up-regulated by transfecting sequence of miR-192mimic. The CCK-8 assay was used to observe the effect of matrine and (or) miR-192 up-regulation on the sensitivity of A549/DDP cells to cisplatin. Results: Data mining Results: showed that there were 11 microRNAs with significant changes in A549/DDP cells compared with cisplatin-sensitive A549 cells (P < 0.05). The changes of miR-192 and miR-194 expression were confirmed in vitro. Compared with untreated A549/DDP cells, matrine treatment reduced the level of miR-192 in A549/DDP cells (P < 0.05). Matrine treatment increased the sensitivity of A549/DDP cells to cisplatin. Up-regulation of miR-192 could antagonize this effect and induce the resistance of A549 cells to cisplatin. Conclusion: Matrine may increase the sensitivity of A549 cells to cisplatin by inhibiting miR-192.

Obstructive Ileocolitis in Patients With Obstructed Colorectal Cancer – A Matched Case Control Study

PURPOSE: Obstructive ileocolitis is an ulcero-inflammatory condition which typically occurs in the ileum or colon proximal to an obstructing colorectal lesion. If left unresolved, it often leads to intestinal perforation. We present a matched case control study of patients with obstructive ileocolitis caused by colorectal cancer to determine if any factors can predict this condition. METHODS: This is a retrospective review of 21 patients with obstructive colorectal cancer and histologically proven obstructive ileocolitis from 2005 to 2015 matched for age and sex with 21 controls with obstructing colorectal cancer without obstructive ileocolitis. RESULTS: The 21 patients with obstructive ileocolitis had a median age of 71 years (range, 52–86 years). The most common presenting symptom was abdominal pain (n = 16, 76.2%), followed by vomiting/nausea (n = 14, 66.7%) and abdominal distension (n = 12, 57.1%). Interestingly, the radiological feature of pneumatosis intestinalis was noted in only 1 case. No significant differences were observed in baseline comorbidities, clinical presentations, or tumor characteristics between the 2 groups. Patients with obstructive ileocolitis were found to have a significantly higher total leucocyte count (17.1 ± 9.4×109/L vs. 12.0 ± 6.8×109/L, P = 0.016), lower pCO2 (32.3 ± 8.2 mmHg vs. 34.8 ± 4.9 mmHg, P = 0.013), lower HCO3 (18.8 ± 4.5 mmol/L vs. 23.6 ± 2.7 mmol/L, P < 0.001), lower base excess (-6.53 ± 5.32 mmol/L vs. -0.57 ± 2.99 mmol/L, P < 0.001) and higher serum lactate levels (3.14 ± 2.19 mmol/L vs. 1.19 ± 0.91 mmol/L, P = 0.007) compared to controls. No radiological features were predictive of obstructive ileocolitis. CONCLUSION: Patients with obstructive ileocolitis tend to present with metabolic acidosis with respiratory compensation, raised lactate, and worse leucocytosis. Radiological features are not useful for predicting this condition.

Effect of microRNA-152 on cholesterol accumulation in RAW264.7 and identification of its functional tar-get genes / 实用医学杂志

Objective To investigate the effect of miR-152 on ox-LDL induced cholesterol accumulation in RAW264.7 macrophages and to verify its target genes. Methods RAW264.7 macrophages were divided into two groups:miR-152 group and negative control group. Total cholesterol(TC),cholesterol ester(CE)concentra- tion and the ratio of CE/TC were observed in the two group by ox-LDL for 48 h. Furthermore,bioinformatics meth-od,dual luciferase reporter assay,real-time quantitative PCR and Western blot were applied to detect the target gene of miR-152. Results As compared with the control group,the contents of TC,CE and the ratio of CE/TC were increased in the miR-152 group. The mRNA and protein expressions of ABCA1 were significantly lower in miR-152 group. Conclusions MiR-152 could inhibit macrophage foam cell formation through decreasing the expres-sion of ABCA1.

Effect of microRNA-152 on cholesterol accumulation in RAW264.7 and identification of its functional tar-get genes / 实用医学杂志

Objective To investigate the effect of miR-152 on ox-LDL induced cholesterol accumulation in RAW264.7 macrophages and to verify its target genes. Methods RAW264.7 macrophages were divided into two groups:miR-152 group and negative control group. Total cholesterol(TC),cholesterol ester(CE)concentra- tion and the ratio of CE/TC were observed in the two group by ox-LDL for 48 h. Furthermore,bioinformatics meth-od,dual luciferase reporter assay,real-time quantitative PCR and Western blot were applied to detect the target gene of miR-152. Results As compared with the control group,the contents of TC,CE and the ratio of CE/TC were increased in the miR-152 group. The mRNA and protein expressions of ABCA1 were significantly lower in miR-152 group. Conclusions MiR-152 could inhibit macrophage foam cell formation through decreasing the expres-sion of ABCA1.

Pre-operative clinical factors predict progression-free survival and tumor recurrence after initial surgery in patients with astrocytomas: a single-center analysis

Pre-operative predictive factors of progression-free survival [PFS] and tumor recurrence after initial surgery are important in counseling patients and decision making. Though PFS after initial surgery in patients with low grade astrocytomas has been described, little is described about PFS in patients with different tumor grades. Our objective was to investigate potential predictive factors of PFS, and devise a scale to predict PFS and tumor recurrence after initial surgery in patients with primary and recurrent astrocytomas of low and high tumor grades. Clinical, radiographic, pathological and treatment data of 62 patients whose initial treatments of primary and recurrent astrocytomas were both surgeries were analyzed, and factors that had significant correlation with PFS was used to devise a scale. Factors significantly related with PFS were: the time from onset of symptoms to clinical and radiological diagnosis of astrocytomas [Spearman correlation coefficient r=0.298, significance level P=0.019] and with the symptoms of seizures [r=0.292, P=0.021]. Patients with age between 30 and 40 years had significant longer PFS than the rest age group [P=0.018, oneway ANOVA]. A simple scale [from 0 to 3 points] comprised of the three factors distinguished four groups of patients with significant different postoperative PFS [0 point, 8.0 months; 1 point, 13.7 months; 2 points, 18.0 months; 3 points, 34.5 months] [P=0.004, oneway ANOVA]. The simple scale we devised comprised of the three pre-operative prognostic factors can significantly distinguish patients with different post-operative survival after initial treatment of astrocytomas with surgery

Effect of endoplasmic reticulum stress on the activation of high glucose-induced monocytes / 中华肾脏病杂志

Objective To observe the effects of endoplasmic reticulum stress (ERS) on the activation of monocytes induced by high glucose and explore the underlying mechanism.Methods The monocyte cell line THP-1 was stimulated with high glucose,and then treated with molecular chaperone betaine.The levels of glucose regulation protein 78 (GRP78) and p-JNK,which were associated with ERS were detected by real-time PCR and Western blotting.The proliferation of the cell line was detected by MTT method.Transwell and immunofluorescence were applied to observe the chemotaxis and phenotype of cells respectively.Results The levels of GRP78 and p-JNK of THP-1 cells stimulated by high glucose were significantly increased compared with the normal control group (all P ＜ 0.05).The proliferation and chemotactic were also enhanced (all P ＜ 0.05).The number of cells in M1 phenotype was increased remarkably (P ＜ 0.05).All the indexes above could be rescued by betaine.Conclusion The activation of THP-1 cells can be induced by high glucose through ERS,while molecular chaperone betaine can reverse the activation.

Biological characteristics of the cerebral venous system and its hemodynamic response to intracranial hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The role of the cerebral venous system (CVS) in intracranial pressure (ICP) regulation remains largely unclear. In the present study, the interaction between ICP and the cerebral venous system and its possible mechanism were investigated with respect to the biological characteristics of the cerebral venous system and its hemodynamic response under increased ICP.</p><p><b>METHODS</b>We created intracranial hypertension animal model, measured and calculated the venous flow velocity and diameter of the outflow terminal of the CVS with color ultrasonic system and recorded the vascular morphology by 3-dimensional anatomical microscopy. Patients who suffered from raised ICP underwent MRI and digital subtraction angiography (DSA) examination to show the length in the vertical direction of the wall of the bridging vein representing the diameter value. Pathological autopsy was performed from bodies of patients who had died from non-cerebral causes to observe the juncture part between the venous sinuses and tributary vertical brain veins.</p><p><b>RESULTS</b>Under increased ICP conditions, venous drainage through the outlet cuff segment, a unique structure between the bridge vein and sinus, was obstructed and in turn venous blood became congested. Therefore, the increased blood volume worsened the pre-existing ICP according to the well-accepted theory regarding volume-pressure relationship. This phenomenon was described as concurrent "venogenic intracranial hypertension", which is characterized by intracranial venous blood stasis responsive to and together with the original increased ICP.</p><p><b>CONCLUSIONS</b>The existence of this special pathophysiological process is prevalent, rather than rare, in various intracranial disorders. This finding would definitely provide new insight into the area of cerebral venous system research.</p>

Effect of regulating endoplasmic reticulum stress on the expression of SET7/9 in the kidneys of db/db mice with diabetic nephropathy / 中华肾脏病杂志

Objective To investigate the effect and significance of regulating endoplasmic reticulum stress on the expression of histone methyltransferases SET7/9 in the kidneys of db/db mice.Methods Db/db mice were randomly divided into two groups according to random number table method:diabetic nephropathy model group (DN group,n=18) and betaine treatment group (DN+B group,n =18),db/m mice were defined as normal control group (NC group,n =18).At the end of 4,8 and 12 weeks,the expression of GRP78,SET7/9,H3K4me2,and monocyte chemoattractant protein 1 (MCP-1) was determined by real-time fluorescence PCR and Western blotting.24-hour urinary protein excretion rate (UPER) and urine MCP-1 were measured by enzyme linked immunosorbent assay (ELISA).The dynamic changes of blood glucose(BG),serum creatinine (Scr),blood urea nitrogen (BUN) were tested by completely automatic biochemistry analyzer.The morphology of kidney was estimated by special staining of periodic acid-schiff (PAS).Results The levels of BG,BUN,UAER and MCP-1 were significantly higher in DN group than those in NC group (P ＜ 0.05),and were in time-dependent manner.Glomerular basement membrane thickening and mesangial cells proliferation began to emerge in DN group at the end of week 4 and mesangial matrix expansion was more obvious at the end of week 12.The mRNA and protein expression of GRP78 and SET7/9 were elevated significantly in DN group as compared to NC group.The H3K4me2 protein expression level was also increased in time-dependent manner.Compared with the DN group,in DN+B group glomerular lesions attenuated and the GRP78 and SET7/9 expression levels obviously decreased (P ＜ 0.05).Furthermore,the levels of BG,BUN,UPER,MCP-1,H3K4me2 in DN+B group were also reduced (P ＜ 0.05).Conclusion Endoplasmic reticulum stress may be the upstream mechanism of mediating the expression of SET7/9 in the kidneys of DN mice.

Correlation between serum proteasome and endothelial dysfunction in patients with uremia / 中华肾脏病杂志

Objective To investigate the correlation between plasma proteasome and endothelial dysfunction in patients with uremia. Methods Forty-five uremic patients who did not receive hemodialysis were defined as A group; seventy-five uremic patients who had received hemodialysis for 6 to 12 months were divided into sufficient hemodialysis group (44 cases,B group)and insufficient hemodialysis group (31 cases,C group).The primary disease of these patients was chronic glomerulonephritis.Fifteen healthy people were defined as healthy control group (D group).The diameter of radial artery lumen (DRL),intima-media thickness (IMT),intima-media area (IMA),endothelium-dependent or independent dilation (EDD or EID) of radial artery in right forearm were detected by diasonography.The levels of 20S proteasome,tumor necrosis factor α (TNF-α),C-reaction protein (CRP) and transforming growth factor β 1 (TGF-β1) of plasma and supernatant of cultured human umbilical veins endothelium (HUVEC) were determined by enzyme linked immunosorbent assay (ELISA).20S proteasome activity was analyzed by special substrate.Results Compared with D group,the level and activity of 20S proteasome,as well as TNF-α,CRP and TGF-β1 in A,B and C groups were significantly increased.Compared with A group,these plasma indices levels were significantly decreased in B group but strongly increased in C group.IMT and IMA were elevated,while DRL,EDD and EID were decreased significantly in A,B and C groups when compared with D group.These parameters were worse in C group than those in A and B groups.After co-culture of HUVEC with above mentioned human uremic serum,the level and activity of 20S proteasome and TNF-α were higher in A,B,C groups than that in D group.In A and C groups,there were negative correlations of EDD with the level or activity of 20S proteasome,TNF-α,CRP and TGF-β1,and there were positive correlations of 20S proteasome level or activity with TNF-α,CRP and TGF-β1. Conclusions 20S proteasome level and activity are significantly increased in uremic patients.There is a close correlation between 20S proteasome and endothelial dysfunction of radial artery.

Role of microRNA-215 in nephropathy of type 2 diabetic db/db mice / 中华肾脏病杂志

Objective To investigate the renal expression changes of microRNA-215(miR-215) and its role in diabetic nephmpathy of type 2 diabetic db/db mice. Methods Fourweek-old diabetic db/db mice and norml control group non-diabetic db/m mice were selected.Real-time PCR was used to detect the relative level of miR-215 at the age of 8,12 and 16 weeks.Catenin beta interacting protein 1 (CTNNBIP1) mRNA and protein level were measured by realtime PCR,WesteRN blotting and immunohistochemisty.A lueiferase reporter assay was used to determine whether CTNNBIP1 was a direct target of miR-215. Results (1)With the growth of db/db mice,the major pathological characteristics of kidney included glomerular hypertrophy,segmental mesangial cells proliferation and mesangial matrix expansion.(2)Compared with the db/m mice,the db/db mice of 8,12 and 16 weeks showed obvious increase in body weight(BW),blood glucose (Glu) and 24 hour urinary albumin excretion (UAE) (P＜0.05,respectively).(3)Compared with the db/m mice,special miR-215 was highly expressed in the kidney of db/db mice and was up-regulated significantly according to the development of DN (P＜0.05).(4)The mRNA and protein expression of CTNNBIPl of kidney were consistently down-regulated in db/db mice than those in controls (P＜0.05,respectively). (5)By luciferase reporter,miR-215 could negatively regulate CTNNBIP1 gene by targeting its 3'-UTR sequence (P＜0.01). Conclusion High expression level of miR-215 plays a potential role in the initiation and progression of DN by down-regulating the expression of CTNNBIPl.

MG132 enhances the renal anti-oxidative ability in diabetic nephropathy rats / 中华肾脏病杂志

Objective To investigate the effects of MG132 on diabetic nephropathy (DN) rats induced with streptozocin. Methods Seventy-two male SD rats were randomly divided into three groups: normal control group (NC, n=24), DN group (n=24) and DN treated with MG132 group (DN+MG132, n=24). At the end of 4, 8 and 12 weeks, 24 hour urinary protein excretion rate (UPER) was detected. Morphology of kidney was examined by special staining of periodic acid-schiff (PAS). Renal 26S proteasome activity was determined by quantifying the hydrolysis of S-LLVY-AMC in a fluorescence reader. Urinary malondialdehyde (MDA) level and renal SOD and GSH-PX activity were detected by commercial kits. Renal SOD, GSH-PX and p47phox mRNA expressions were determined by real-time fluorescence PCR. Renal p47phox protein expression wasdetermined by Western blotting. Results Compared with NC group, the DN group showed a significant increased of UPER at week 4, 8, 12 (all P<0.05), of mesangium proliferation and mesangial matrix expansion at week 12. In DN+MG132 group, UPER was significantly decreased compared with DN group at the end of 4, 8 and 12 weeks (P<0.05, respectively), and the glomeruler pathological alteration induced by diabetes was attenuated. Increased renal 26S proteasome activity in DN rats was significantly inhibited after MC132 administration (P<0.05). Moreover, renal p47phox mRNA expression in DN group was 155%, 149% and 120% more than those in NC group at 3 time points (all P<0.05), and so was the renal p47phox protein expression, 139%, 152% and 186% more (all P<0.05). Urinary MDA levels in DN group were 1.95-, 2.04-and 2.62-folds more than those in NC group (all P<0.05). In addition, compared with NC group at 3 time points, in DN group, renal SOD activity was decreased by 23.09%, 33.59% and 53.31% (all P<0.05); renal GSH-PX activity was decreased by 28.57%, 33.06% and 48.76% (all P< 0.05); renal SOD mRNA was decreased by 38.09%, 61.44% and 76.53% (all P<0.05); renal GSH-PX mRNA group was decreased by 29.16%, 37.26% and 62.40% (all P<0.05). Compared with DN group, renal p47phox mRNA and protein expression, and urinary MDA levels were significantly lower in DN+MG132 group (all P<0.05); renal SOD and GSH-PX activity as well as mRNA expression were significantly increased in DN+MG132 group (all P<0.05). Conclusions MG132 treatment can provide renoprotection for DN rats effectively maybe through enhancing renal anti-oxidative ability.

Relationship between invasiveness and expression of ER、PGTT、bFGF in human prolactinomas / 基础医学与临床

Objective To explore the relationship between invasive growth and expression of ER、PTTG、bFGF in human prolactinomas.Methods Fourty-six prolactinomas specimens were collected and divided into invasive group and non-invasive group.Expressions of ER、PTTG、bFGF were examined by immunocytochemical method.Total RNA was extracted from specimens and ER-mRNA and PTTG-mRNA were detected by RT-PCR.Results IA of protein expression of ER、bFGF、PTTG in invasive prolactinomas was seperately 5385.1?1348.6、9874.2?2143.7、7938.5?1436.5;The optical density ratio of ER-mRNA and PTTG-mRNA was 0.71 and 0.83,difference between invasive group and non-vasive group was significant.Conclusions ER、PTTG、bFGF in human prolactinomas closely correlated with invasiveness of prolactinomas,and may play important function in prolactinomas.

Using green fluorescent protein as a reporter to monitor elimination of selectable marker genes from transgenic plants / 生物工程学报

In genetic modification of plants, once the transformants are obtained, selection markers are no longer required in mature plants. At present, the Cre/lox site-specific recombination system is most widely used to eliminate the selectable marker genes from the transgenic plants. In this study, attempt was made to favour the selection of marker-free plants in the re-transformation method. Green fluorescent protein (GFP) can be directly visualized in living cells, tissues or organisms under UV illumination. This advantage of GFP is exploited in the development of a practical approach in which GFP is used as a visual marker to monitor the removal of the selectable marker gene from transgenic plants. For that purpose, the pGNG binary vector was constructed, in which the GFP gene (gfp) was linked to the expression cassette Nos P-nptII-NosT and the two units were cloned between two directly-orientated lox sites. The CaMV 35S promoter was placed before the first lox site and used to drive GFP expression. The beta-glucuronidase gene (gus) of Escherichia coli was cloned behind the second lox site without a promoter, thus would not be expressed in this position. Tobacco plants were first transformed with pGNG and selected on kanamycin (Kan)-containing media. Regenerated transgenic shoots were readily singled out by GFP fluorescence. The GFP-expressing plants were then re-transformed with pCambia1300-Cre containing hygromycin phosphotransferase gene (hpt) as a selectable marker gene. The Cre-mediated recombination resulted in the elimination of lox-flanked genes, herein gfp and nptII, from the plant genome and brought the GUS gene next to the 35S promoter. Our data demonstrated that transgenic plants free of nptII were easily selected by monitoring the loss of green fluorescence, and at the same time, GUS (here as a target protein) was expressed in the nptII-free plants. Finally, hpt and cre were removed from the progenies of the nptII-free plants by gene segregation.

The study of biological properties of gliomas / 中国医学科学院学报

In order to explore the new methods of biological treatment of human gliomas, this project is to study the biological properties of gliomas from four different aspects, the results show that there is a IL-6 autocrine loop in human gliomas and the growth of gliomas will be inhibited when the autocrine loop is broken. There is a magnificent predominant expression of Th2 cytokines in human gliomas and human glioma cells, the switching of Th2 to Th1 can inhibit the proliferation of glioma cells. The dosage of 100 micrograms/ml of erythromycin is the best of therapeutic effect. Angiostatin can not only inhibit the vascular endothelial growth, but also have the inhibitory role on the growth of glioma cells in vivo. The above studies have provided some new ideas and will be very helpful for the treatment of glioma patients.