Objective To investigate the advantages and efficacy of traction with titanium clips in endoscopic submucosal dissection(ESD)for large laterally spreading tumor(LST)in rectum and sigmoid colon.Methods 67 patients with large sigmoid or rectal LST underwent ESD from January 2018 to June 2022 were analyzed retrospectively,including 32 patients in Group A and 35 patients in Group B.Group A was treated with clip-line traction and group B was treated with traditional ESD.The size of lesion,the total operation time,the submucosal dissection time,submucosal dissection rate,submucosal injection number,en bloc resection rate,R0 resection rate,curative resection rate and complications of the two groups were compared.Results LST-G-M was the most common type and villous adenoma was the main pathology in both groups.There were no differences in en bloc resection rate,R0 resection rate and incidence of complications between the two groups.The average size of group A was(13.6±8.4)cm2,significantly larger than that in group B(9.3±4.7)cm2,the total operation time was(42.3±10.3)min in group A,significantly shorter than that in group B(47.9±10.1)min,submucosal dissection time was(30.7±8.2)min in group A,significantly shorter than that in group B(36.1±7.6)min,submucosal injection number was(2.7±1.1)times in group A,significantly less than that in group B(3.5±1.2)times,submucosal dissection rate was(0.4±0.2)cm2/min in group A,significantly faster than that in group B(0.2±0.1)cm2/min,the differences were statistically significant(P<0.05).Conclusion Compared with traditional ESD,clip-line traction can provide a better surgical field and more effective dissection for large LST in rectum and sigmoid colon.

Objective To observe the effect of electroacupuncture at Baihui (DU20) and Shenting (DU24) on brain functional activity and working memory of rats with vascular cognitive impairment (VCI). Methods Eighteen Sprague-Dawley rats were included, in which twelve rats were ligated bilateral common carotid arteries and six rats were not ligated (sham group). The modeled rats were randomly divided into model group (n = 6) and electroacupuncture group (n = 6). The electroacupuncture group received electroacupuncture at Baihui and Shenting for four weeks. They were assessed with Y maze and Morris water maze before and after intervention, and scaned with resting-state functional magnetic resonance imaging after intervention to calculate regional homogeneity (ReHo). Results Compared with the sham group, alternation rate of Y maze decreased (P < 0.001), and escape latency of Morris water maze increased (P < 0.05) in the model group and the electroacupuncture group before intervention. Compared with the model group, alternation rate of Y maze increased (P < 0.05), and escape latency of Morris water maze decreased (P < 0.05) after intervention in the electroacupuncture group. Compared with the sham group, ReHo of bilateral hippocampus, olfactory cortex, sensory cortex and auditory cortex, and left striatum decreased in the model group; compared with the model group, ReHo of bilateral prefrontal lobe, hippocampus and olfactory cortex, and left amygdala increased in the electroacupuncture group. Conclusion Electroacupuncture at Baihui and Shenting can improve the memory function of VCI rats, which may be related to the functional activities of prefrontal lobes, hippocampus and amygdala.

Inflammatory reaction dominated by defense response will arise against infection and trauma. As an important proinflammatory cytokine, high mobility group box 1 (HMGB1) is widely expressed in all nuclear cells to mediate the inflammatory response. However, the biological functions of HMGB1 in inflammation vary depending on the type of HMGB1 protein modification and the localization in the cell. HMGB1 protein will be modified as acetylation of lysine residues, methylation of lysine residues, oxidation of cysteine residues, phosphorylation of serine residues, glycosylation of asparagine residues, adenosine diphosphate-ribosylation and lactylation of the protein in the nucleus, migrate from the nucleus to the cytoplasm, and release into the extracellular compartment. Extracellular HMGB1 can bind to receptors for advanced glycation end products (RAGE) and Toll-like receptors, activate cells and regulate inflammatory responses. The authors review the research progress in regulatory mechanism of HMGB1 in inflammation response from aspects of its post-translational modifications, releases, biological roles and binding receptors, hoping to provide theoretical basis for finding the targets of inflammation intervention.

Objectives:To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer.Methods:The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ 2 test. Results:Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months, P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%, P<0.05;32.9% vs. 21.9%, P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%, P>0.05). Conclusions:The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients′ compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.

Objectives:To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer.Methods:The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ 2 test. Results:Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months, P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%, P<0.05;32.9% vs. 21.9%, P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%, P>0.05). Conclusions:The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients′ compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.

Objective:To investigate the changes of brain energy metabolism and cognitive function in mice with specifically knocking out AMP-activated protein kinase α1 subunit ( AMPKα1) gene in the excitatory neurons by Cre-loxP recombination system. Methods:Sixteen 6-month-old mice with genotype AMPKα1 flox/flox/Camk2a-Cre/ERT2 obtained by hybrid breeding were randomly divided into AMPKα1 knockout group ( n=8) and AMPKα1 wild-type group ( n=8). Mice in the AMPKα1 knockout group were intraperitoneally injected 0.1 mL tamoxifen (20 mg/mL, dissolved in corn oil) daily for a consecutive 5 d to control AMPKα1 gene knockout in the excitatory neurons; and mice in the AMPKα1 wild-type group were intraperitoneally injected 0.1 mL corn oil daily for a consecutive 5 d. Seven d after that, Morris water maze and T maze experiments were employed to detect the spatial learning and memory abilities and spatial working memory of these mice; chemical exchange saturation transfer imaging (CEST) was used to observe the glucose metabolism in the hippocampus and cortex surrounding the hippocampus; Western blotting was used to detect the AMPKα1 and glutamate receptor 1 (GluR1) protein expressions in the hippocampus and cortex surrounding hippocampus of two groups. Results:(1) Morris water maze showed that, as compared with those in the AMPKα1 wild-type group, mice in the AMPKα1 knockout group had significantly prolonged escape latency ([13.90±3.72] s vs. [22.40±6.28] s; [11.95±3.86] s vs. [22.39±9.77] s]) on the 3 rd and 4 th d of experiment, statistically decreased times crossing the platform ([5.25±1.83] times vs. [1.75±1.28] times, P<0.05). (2) T-maze experiment showed that as compared with that of the AMPKα1 wild-type group, the free alternation rate in mice of the AMPKα1 knockout group was significantly decreased ([73.21±9.16]% vs. [48.21±11.29]%, P<0.05). (3) CEST showed that the glucose metabolism levels in the hippocampus and cortex surrounding the hippocampus of AMPKα1 knockout group were significantly lower than those in AMPKα1 wild-type group (1.51±0.81 vs. 2.77±0.67; 1.31±0.83 vs. 2.42±0.95, P<0.05). (4) Western blotting showed that the AMPKα1 and GluR1 protein expressions in the hippocampus and cortex surrounding the hippocampus of the AMPKα1 wild-type group were significantly higher than those of the AMPKα1 knockout group (AMPKα1: 0.70±0.05 vs. 0.49±0.03, 0.98±0.04 vs. 0.64±0.06; GluR1: 1.22±0.18 vs. 0.60±0.11, 0.96±0.08 vs. 0.79±0.04, P<0.05). Conclusion:Specifically knocking out AMPKα1 in excitatory neurons can result in abnormal glucose metabolism in the brain of mice, and thus cause cognitive dysfunction, whose mechanism may be related to excitatory synaptic disorder caused by energy metabolism disorder.

Objective:To investigate the mechanism of learning and memory impairment of apolipoprotein E -/- ( ApoE-/-) mice after transient global cerebral ischemia by diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). Methods:Ten-week-old C57BL/6(WT) mice and ApoE-/- mice were randomly divided into WT sham-operated group ( n=8), WT 7 d group ( n=12) and WT 30 d group ( n=12), and ApoE-/- sham-operated ( n=8), ApoE-/- 7 d group ( n=12) and ApoE-/- 30 d group ( n=12). The mice in the WT 7 d group, WT 30 d group, ApoE-/- 7 d group, and ApoE-/- 30 d group received bilateral common carotid artery ischemia-reperfusion injury, while mice in the WT sham-operated group and ApoE sham-operated group only stripped the blood vessels without ligation. On the 7 th and 30 th d of modeling, Morrris water maze test was employed to detect the learning and memory abilities of these mice; DTI was used to detect the fractional anisotropy (FA) values in the bilateral hippocampus of mice, and MRS was used to detect the contents of choline complex (Cho) and N-acetylaspartate (NAA) in the bilateral hippocampus of mice. Results:(1) On 2 nd, 3 rd, and 4 th d of water maze experiment, the escape latency of mice in ApoE-/- 7 d group was significantly prolonged as compared with that in the ApoE-/- sham-operated group and WT 7 d group ( P<0.05); since the 3 rd d of water maze experiment, the escape latency of mice in ApoE-/- 30 d group was significantly prolonged as compared with that in WT 30 d group ( P<0.05). The number of times crossing platform in ApoE-/- 7 d group was significantly smaller than that in WT 7 d group, and the residence time in the third quadrant was significantly shorter ( P<0.05); the number of times crossing platform in ApoE-/- 30 d group were significantly smaller as compared with that in the WT 30 d group, and the residence time in the third quadrant was significantly shortened ( P<0.05). (2) DTI results showed that there was no significant difference in bilateral hippocampal FA values between ApoE-/- 7 d group and WT 7 d group ( P>0.05); the bilateral hippocampal FA values of mice in the ApoE-/- 30 d group were statistically lower than those in WT 30 d group ( P<0.05). (3) MRS results showed that the relative contents of hippocampal Cho and NAA in the ApoE-/- 7 d group were significantly lower than those in the WT 7 d group, and the relative contents of hippocampal Cho and NAA in the ApoE-/- 30 d group were significantly lower than those in the WT 30 d group ( P<0.05). Conclusion:ApoE-/- mice have poor learning and memory abilities after transient global cerebral ischemic injury, whose mechanism is closely related to the damage of hippocampal white matter fibers and abnormal metabolism of nerve cells.

Brain glucose metabolism disorder is one of the pathophysiological features of Alzheimer's disease (AD), in which aerobic glycolysis (Warburg effect) metabolic pathway abnormality is one of the causes of early cognitive impairment in AD, and improving brain energy metabolism has become an important strategy to prevent AD. AMP-activated protein kinase (AMPK) is a central hub regulating glucose metabolism, the most sensitive molecular compound for sensing fluctuations of energy levels in the body. Activation of AMPK can affect the Warburg effect and its key rate-limiting enzyme activity, regulate brain glucose metabolism involved in the pathogenesis of AD, to achieve the purpose of delaying AD progression and improving cognitive function in early clinical stage. In this review, we will discuss the pathogenesis of AD and targeting of AMPK from the perspective of Warburg effect in glucose metabolism.

To explore the mechanism for changes in brain microstructure in long-term abstinent from methamphetamine-dependence by using the diffusion tensor imaging (DTI).
 Methods: A total of 26 patients with long-term abstinent methamphetamine-dependence, whose abstinence time more than 14 months, and 26 normal controls all underwent cognitive executive function tests and DTI scans. We used voxel-based analysis to compare the fractional anisotropy (FA) and mean diffusivity (MD) to obtain the abnormal brain regions of DTI parameters between the two groups. Spearman correlation analysis was used to explore the correlation between FA, MD of the brain regions with abnormal parameters and cognitive executive function tests.
 Results: There were no statistical differences in the cognitive executive function tests between the two groups (P>0.05). Compared with the normal control group, the long-term abstinent from methamphetamine-dependence group showed the decreased FA in the right precuneus, right superior frontal gyrus, right calcarine, left inferior temporal gyrus and the increased MD in the right triangular part of inferior frontal gyrus, right precuneus, right posterior cingulate, right middle temporal gyrus, bilateral middle occipital gyrus, left superior parietal lobule, and lobule VIII of cerebellar hemisphere. The MD values of the right middle temporal gyrus in the long-term abstinent group were negatively correlated with the number of completions within 60 seconds (r=-0.504) and within 120 seconds (r=-0.464) .
 Conclusion: The DTI parameters in multiple brain regions from the methamphetamine-dependence patients are still abnormal after a long-term abstinence. DTI can provide imaging evidence for brain microstructural abnormalities in long-term abstinent from methamphetamine-dependence.
Amphetamine-Related Disorders ; Anisotropy ; Brain ; Diffusion Tensor Imaging ; Humans ; Methamphetamine

Stroke at the acute stage is a major cause of disability in adults, and is associated with dysfunction of brain networks. However, the mechanisms underlying changes in brain connectivity in stroke are far from fully elucidated. In the present study, we investigated brain metabolism and metabolic connectivity in a rat ischemic stroke model of middle cerebral artery occlusion (MCAO) at the acute stage using F-fluorodeoxyglucose positron emission tomography. Voxel-wise analysis showed decreased metabolism mainly in the ipsilesional hemisphere, and increased metabolism mainly in the contralesional cerebellum. We used further metabolic connectivity analysis to explore the brain metabolic network in MCAO. Compared to sham controls, rats with MCAO showed most significantly reduced nodal and local efficiency in the ipsilesional striatum. In addition, the MCAO group showed decreased metabolic central connection of the ipsilesional striatum with the ipsilesional cerebellum, ipsilesional hippocampus, and bilateral hypothalamus. Taken together, the present study demonstrated abnormal metabolic connectivity in rats at the acute stage of ischemic stroke, which might provide insight into clinical research.
Acute Disease ; Animals ; Brain ; diagnostic imaging ; metabolism ; Brain Mapping ; Disease Models, Animal ; Fluorodeoxyglucose F18 ; Glucose ; metabolism ; Infarction, Middle Cerebral Artery ; diagnostic imaging ; metabolism ; Male ; Neural Pathways ; diagnostic imaging ; metabolism ; Positron-Emission Tomography ; Radiopharmaceuticals ; Random Allocation ; Rats, Sprague-Dawley