elationship between preoperative fasting plasma glucose and postoperative pulmonary complications after lung resection in type 2 diabetic patients / 中国胸心血管外科临床杂志

@#Objective     To explore the relationship between preoperative fasting plasma glucose (FPG) and postoperative pulmonary complications (PPCs) in type 2 diabetic patients undergoing elective thoracoscopic lung resection, and provide a reference for prediction and prevention of PPCs in the clinic. Methods     A retrospective analysis was performed on the type 2 diabetic patients who underwent elective thoracoscopic lung resection for the first time in our hospital from January 2017 to March 2021. According to the level of FPG one day before the operation, the patients were divided into three groups: a hypoglycemia group (<6.1 mmol/L), a medium level blood glucose group (≥6.1 mmol/L and <8.0 mmol/L) and a high blood glucose group (≥8.0 mmol/L). Besides, the patients were divided into a PPCs group and a non-PPCs group according to whether PPCs occurred. The risk factors for PPCs were analyzed by logistic regression analysis, and the predictive value of preoperative FPG level on PPCs was estimated by the area under the receiver operating characteristic curve (AUC). Results     A total of 130 patients were included, including 75 (57.7%) males and 55 (42.3%) females with an average age of 63.5±9.0 years. Logistic regression analysis showed that compared to non-PPCs patients, the level of preoperative FPG (P=0.023) and smoking history ratio (P=0.036) were higher and the operation time was longer (P=0.004) in the PPCs patients. High FPG level on preoperative day 1 and longer operation time were associated with PPCs risk. Besides, the preoperative FPG of 6.79 mmol/L was the threshold value to predict the occurrence of PPCs [AUC=0.653, 95%CI (0.559, 0.747), P=0.003]. Conclusion     There is a certain correlation between preoperative FPG level and postoperative PPCs, which may be used as an index to predict the occurrence of PPCs.

Effect of Chaihu Guizhitang on Triple-negative Breast Cancer Cells： Based on HIF-1α/VEGFA Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Chaihu Guizhitang on triple-negative breast cancer （TNBC） cells based on hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor A （VEGFA） signaling pathway. MethodTNBC xenograft model was established and the cells were randomized into model group， capecitabine group （0.2 mg·kg-1）， Chaihu Guizhitang low-dose group， medium-dose group， and high-dose group （10.62， 21.23， 42.46 g·kg-1）， with 10 mice in each group. After 21 days of medication， the content of tumor necrosis factor-α （TNF-α） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. The expression of HIF-1α mRNA was detected by real-time fluorogenic quantitative polymerase chain reaction （real-time PCR）. Immunohistochemistry （IHC） was employed to detect the expression of HIF-1α， TNF-α， and VEGFA in tumor tissues， and CD34 staining to examine the angiogenesis in tumor tissues. Microvessel density （MVD） was calculated， and the protein expression of HIF-1α， VEGFA， and epidermal growth factor receptor （EGFR） in tumor tissues was measured by Western blot. ResultCompared with the model group， the rest four groups showed low levels of TNF-α （P<0.01）， HIF-1α mRNA （P<0.01）， expression of HIF-1α， TNF-α， VEGFA， and CD34 in cells， and MVD （P<0.05， P<0.01）， and low protein levels of HIF-1α， VEGFA， and EGFR （P<0.01）. Compared with capecitabine group， medium-dose and high-dose Chaihu Guizhitang decreased the level of TNF-α （P<0.01）， HIF-1α mRNA （P<0.01）， expression of HIF-1α， TNF-α， and VEGFA in cells （P<0.01）， CD34 expression， MVD， and protein levels of HIF-1α， VEGFA， and EGFR （P<0.01）. ConclusionChaihu Guizhitang may inhibit the angiogenesis in TNBC cells by regulating the expression of HIF-1α/VEGFA signaling pathway， thus exerting anti-tumor effect.

Targeting a cryptic allosteric site of SIRT6 with small-molecule inhibitors that inhibit the migration of pancreatic cancer cells

SIRT6 belongs to the conserved NAD+-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD+. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC50 of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

A high-efficiency and versatile CRISPR/Cas9-mediated HDR-based biallelic editing system / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9), the third-generation genome editing tool, has been favored because of its high efficiency and clear system composition. In this technology, the introduced double-strand breaks (DSBs) are mainly repaired by non-homologous end joining (NHEJ) or homology-directed repair (HDR) pathways. The high-fidelity HDR pathway is used for genome modification, which can introduce artificially controllable insertions, deletions, or substitutions carried by the donor templates. Although high-level knock-out can be easily achieved by NHEJ, accurate HDR-mediated knock-in remains a technical challenge. In most circumstances, although both alleles are broken by endonucleases, only one can be repaired by HDR, and the other one is usually recombined by NHEJ. For gene function studies or disease model establishment, biallelic editing to generate homozygous cell lines and homozygotes is needed to ensure consistent phenotypes. Thus, there is an urgent need for an efficient biallelic editing system. Here, we developed three pairs of integrated selection systems, where each of the two selection cassettes contained one drug-screening gene and one fluorescent marker. Flanked by homologous arms containing the mutated sequences, the selection cassettes were integrated into the target site, mediated by CRISPR/Cas9-induced HDR. Positively targeted cell clones were massively enriched by fluorescent microscopy after screening for drug resistance. We tested this novel method on the amyloid precursor protein (APP) and presenilin 1 (PSEN1) loci and demonstrated up to 82.0% biallelic editing efficiency after optimization. Our results indicate that this strategy can provide a new efficient approach for biallelic editing and lay a foundation for establishment of an easier and more efficient disease model.

Role of Yes-associated protein 1 in acute lung injury in septic mice: the relationship with ferroptosis / 中华麻醉学杂志

Objective:To evaluate the role of Yes-associated protein 1 (YAP1) in acute lung injury (ALI) and the relationship with ferroptosis in septic mice.Methods:Twenty-four male wild-type mice and 24 YAP1 conditional knockout mice, aged 9-10 weeks, weighing 22-25 g, were divided into 2 groups ( n=12 each) using a random number table method: wild-type sham operation group (WT+ Sham group) and wild-type sepsis-induced ALI group (WT+ ALI group); YAP1 conditional knockout sham operation group (CKO+ Sham group) and YAP1 conditional knockout sepsis-induced ALI group (CKO+ ALI group). The sepsis-induced ALI model was developed by cecal ligation and perforation (CLP) in anesthetized animals.The bronchoalveolar lavage fluid (BALF) was collected at 24 h after CLP to determine the protein concentration (by bicinchoninic acid method) and concentrations of interleukin-1beta (IL-1β) and tumor necrosis factor-α (TNF-α) (by enzyme-linked immunosorbent assay). Mice were then sacrificed, and the lung tissues were obtained for examination of ultrastructure (using a transmission electron microscope) and for determination of wet/dry lung weight ratio (W/D ratio), contents of Fe 2+ , malondialdehyde (MDA) and glutathione (GSH) (by colorimetric assay), and expression of YAP1, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) (by Western blot). Results:Compared with WT+ Sham group, the concentrations of protein in BALF, IL-1β and TNF-α were significantly increased, W/D ratio and contents of Fe 2+ and MDA were increased, GSH contents were decreased, the expression of GPX4 and SLC7A11 was down-regulated, ACSL4 expression was up-regulated ( P<0.05), alveolar epithelial cells showed characteristic changes of ferroptosis with mitochondrial shrinkage and decreased mitochondrial cristae in WT+ ALI group.Compared with WT+ CLP and CKO+ Sham groups, the concentrations of protein in BALF, IL-1β and TNF-α were significantly increased, W/D ratio and contents of Fe 2+ and MDA were increased, GSH contents were decreased, the expression of GPX4 and SLC7A11 was down-regulated, ACSL4 expression was up-regulated ( P<0.05), and the mitochondria in alveolar epithelial cells in lung tissues shrank obviously, and the mitochondrial cristae were reduced or even disappeared in CKO+ CLP group ( P<0.05). Conclusions:YAP1 is involved in the endogenous protective mechanism against ALI, which is related to inhibition of ferroptosis in septic mice.

Relationship between Nrf2 and ferroptosis during lung ischemia-reperfusion in rats / 中华麻醉学杂志

Objective:To evaluate the relationship between nuclear factor E2-related factor 2 (Nrf2) and ferroptosis during lung ischemia-reperfusion (I/R) in rats.Methods:Fifty-four healthy male Sprague-Dawley rats, weighing 220-250 g, were divided into 3 groups ( n=18 each) using a random number table method: sham operation group (Sham group), lung I/R group (IR group), and lung I/R+ Nrf2 agonist sulforaphane group (IR+ SFP group). Lung I/R model was developed by clamping the left pulmonary hilum for 60 min followed by 120 min of reperfusion.In IR+ SFP group, SFP 500 μg/kg was intraperitoneally injected at 3 days before lung ischemia once a day for 3 consecutive days, and the model was developed at 2 h after the end of administration.The rats were sacrificed at the end of reperfusion, and the bronchoalveolar lavage fluid (BALF) was collected to determine the protein concentration (using bicinchoninic acid method), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations (by enzyme-linked immunosorbent assay). The animals were then sacrificed, and lung tissue specimens were harvested for microscopic examination of the pathological changes (with a transmission electron microscope) and for determination of wet/dry weight (W/D) ratio, contents of iron, malondialdehyde (MDA) and glutathione (GSH) (by chemical colorimetric) and expression of nuclear Nrf2, glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) (by Western blot). Results:Compared with Sham group, the concentrations of protein, IL-6 and TNF-α in BALF, W/D ratio, and contents of Fe 2+ and MDA were significantly increased, GSH content was decreased, GPX4 expression was down-regulated, the expression of nuclear Nrf2and ACSL4 was up-regulated ( P<0.05), and the mitochondrial morphology of type Ⅱalveolar epithelial cells showed the characteristic changes of ferroptosis, including the presence of smaller mitochondria and reduced cristae in IR group.Compared with IR group, the concentrations of protein, IL-6 and TNF-α in BALF, W/D ratio, and contents of Fe 2+ and MDA were significantly decreased, GSH content was increased, the expression of nuclear Nrf2 and GPX4 expression was up-regulated, ACSL4 expression was down-regulated ( P<0.05), and the pathological changes of lung tissues were significantly attenuated in IR+ SFP group. Conclusions:Nrf2 can inhibit ferroptosis during lung I/R and is involved in the endogenous protective mechanism in rats.

Deep learning: a new multifaceted tool assisting biomedical research and clinical diagnosis / 国际生物医学工程杂志

Artificial intelligence (AI) is one of the hottest research topics. The development of AI technology not only brings convenience to people's lives, but also integrates with other frontier fields to aid in data processing and result prediction. Deep learning is one of the emerging technologies that demonstrate outstanding performances. In this paper, the wide application of deep learning technology in many fields of biomedicine was summarized, common methods and models were briefly introduced including artificial neural network, deep neural network, convolutional neural network and recurrent neural network. Besides, the application of deep learning in biomedical image analysis, omics data processing and protein spatial structure prediction was summarized, and its limitations and development prospects in the above applications were briefly discussed.

Targeting RAS phosphorylation in cancer therapy: Mechanisms and modulators

RAS, a member of the small GTPase family, functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state. RAS gain-of-function mutations are one of the leading causes in human oncogenesis, accounting for ∼19% of the global cancer burden. As a well-recognized target in malignancy, RAS has been intensively studied in the past decades. Despite the sustained efforts, many failures occurred in the earlier exploration and resulted in an 'undruggable' feature of RAS proteins. Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins. Therefore, the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties. A better understanding of RAS phosphorylation can contribute to future therapeutic strategies. In this review, we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways. Importantly, the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.

Construction and verification of an intelligent measurement model for diabetic foot ulcer / 中南大学学报(医学版)

OBJECTIVES@#The measurement of diabetic foot ulcers is important for the success in diabetic foot ulcer management. At present, it lacks the accurate and convenient measurement tools in clinical. In recent years, artificial intelligence technology has demonstrated the potential application value in the field of image segmentation and recognition. This study aims to construct an intelligent measurement model of diabetic foot ulcers based on the deep learning method, and to conduct preliminary verification.@*METHODS@#The data of 1 042 diabetic foot ulcers clinical samples were collected. The ulcers and color areas were manually labeled, of which 782 were used as the training data set and 260 as the test data set. The Mask RCNN ulcer tissue color semantic segmentation and RetinaNet scale digital scale target detection were used to build a model. The training data set was input into the model and iterated. The test data set was used to verify the intelligent measurement model.@*RESULTS@#This study established an intelligent measurement model of diabetic foot ulcers based on deep learning. The mean average precision@.5 intersection over union (mAP@.5IOU) of the color region segmentation in the training set and the test set were 87.9% and 63.9%, respectively; the mAP@.5IOU of the ruler scale digital detection in the training set and the test set were 96.5% and 83.4%, respectively. Compared with the manual measurement result of the test sample, the average error of the intelligent measurement result was about 3 mm.@*CONCLUSIONS@#The intelligent measurement model has good accuracy and robustness in measuring the diabetic foot ulcers. Future research can further optimize the model with larger-scale data samples.

Clinical analysis of bone mineral density in patients with newly diagnosed untreated systemic lupus erythematous / 中华风湿病学杂志

Objective:The study was aimed to investigate the bone mineral density (BMD) status of newly diagnosed systemic lupus erythematous (SLE) patients.Methods:Newly diagnosed SLE patients and healthy controls in Peking University Third Hospital from 2014 to 2018 were enrolled into this cross-sectional study. Medical records including systemic lupus erythematosus disease activity index (SLEDAI)-2000 and BMD of the lumbar vertebrae and hips measured by dual-energy X-ray absorptiometry were collected. Patients were divided into normal and low BMD groups. Parameters were compared by Student- t test, Mann-Whitney U test and χ 2 test. Results:Eighty-nine patients and 20 healthy controls were included. Approximately 52.8% of the SLE patients had low BMD. Compared to the healthy control group, the BMD of lumbar spine and hip was obviously lower than in the newly diagnosed SLE group[(0.97±0.14) g/cm 2, (1.08±0.10) g/cm 2, t=3.548, P<0.01; (0.88±0.15) g/cm 2, (1.00±0.08) g/cm 2, t=3.878, P<0.01]. The BMD of lumbar spine and hip in the low BMD group was lower than that in the normal BMD group [(0.88±0.10) g/cm 2, (0.80±0.11) g/cm 2; (1.07±0.11) g/cm 2, (0.97±0.13) g/cm 2, respectively]. Compared with the normal BMD group, the body mass index (BMI) was significantly lower [(19.2±2.0) kg/m 2, (23.2±3.6) kg/m 2 respectively, t=3.678, P<0.01], the disease duration was longer [(45.7±7.7) weeks, (16.0±19.5) weeks, respectively, t=-3.306, P<0.01). Patients with low BMD tended to have lower 25-hydroxy-vitamin-D(25-OH-VD 3) level and higher bone metabolism marker levels (Degradation products of collagen B) [(9±5) nmol/L vs (12±7) nmol/L, t=1.385, P>0.05; 0.62(0.21, 1.61) ng/ml vs 0.43(0.19, 0.88) ng/ml, Z=0.624, P>0.05], although their differences didn't reach the statistical significant difference. Conclusion:Newly diagnosed SLE patients' BMD is lower than the healthy people. About 52.8% newly diagnosed untreated SLE patients have low BMD. Lower BMI and longer disease duration are their clinical characteristics. High bone metabolism marker levels, low 25-hydroxy-vitamin-D level might have clinical significance, although the current findings do not find statistically significant difference. Large sample size is required for subsequent research analysis.

Effect of oxycodone hydrochloride injection on focal cerebral ischemia-reperfusion injury in rats / 中华急诊医学杂志

Objective:To investigate the effect of oxycodone hydrochloride injection pretreatment on focal cerebral ischemia-reperfusion injury in rats.Methods:Seventy-two male SD rats weighing 200-250 g were randomly divided into 3 groups( n=24 each group): sham operation group (sham group), focal cerebral I/R group (I/R group), and oxycodone hydrochloride injection group (Oxy group). Focal cerebral I/R was induced by middle cerebral artery occlusion for 2 h followed by reperfusion. In the Oxy group, oxycodone hydrochloride 0.5 mg/kg was injected iv at 5 min before ischemia. While the same volume of saline (1 mL) was injected in the sham group and I/R group. The neurological deficit score (NDS) was assessed at 24 h of reperfusion, the rats were then sacrificed, and their brains were immediately removed for determination of brain water content and the infarct volume, and the histopathological changes were observed after HE staining. The levels of cytokines (TNF-α, IL-1β and IL-10) in the ischemia cortex were quantified by ELISA. MPO activity in the ischemia cortex was assessed. Western blot was used to detect the expression of NF-κB in the ischemia cortex. The data were analyzed using SPSS 20.0 software, multiple-group comparisons were performed using one-way ANOVA, and LSD- t test was used for pairwise comparison between groups. A P<0.05 was considered statistically significant different. Results:Compared with the sham group, NDS, brain water content, relative infarction volume and rate of nerve cell necrosis were significantly increased in the I/R and Oxy groups (all P<0.05). Levels of TNF-α, IL-1β, IL-10, NF-κB and the activities of MPO were increased in the ischemia cortex (all P<0.05). Compared the Oxy group with the I/R group, NDS, brain water content, relative infarction volume and rate of nerve cell necrosis were significantly decreased [(1.7±0.9) vs (2.6±1.1);(79.2±2.4)% vs (84.7±4.2)%; (23.0±5.4)% vs (34.8±6.0)%; (25.2±12.4)% vs (54.8±14.8)%, all P<0.05]. The levels of TNF-α, IL-1β, relative expression of NF-κB, and the activities of MPO were significantly decreased in the ischemia cortex [(4.4±1.2) pg/mg vs (6.5±1.2) pg/mg; (5.4±0.7) pg/mg vs (7.8±0.8) pg/mg; (0.83±0.11) vs (1.23±0.33); (0.27±0.09) U/g vs (0.36±0.14) U/g, all P<0.05] , while the concentration of IL-10 was significantly increased [(20.9±4.5) pg/mg vs (9.2±1.6) pg/mg, t=6.036, P=0.000 1]. Conclusions:Oxycodone hydrochloride can attenuate focal cerebral I/R injury through inhibiting NF-κB activity.

Role of Erbin in muramyl dipeptide-induced inflammatory responses in macrophages of mice / 中华麻醉学杂志

Objective:To evaluate the role of ErbB2-interacting protein (Erbin) in muramyl dipeptide (MDP)-induced inflammatory responses in the macrophages of mice.Methods:Erbin gene knockout RAW264.7 cell line (Erbin -/ -RAW264.7) was constructed by CRISPR/CAS9 gene-editing technology.RAW264.7 cells were cultured in vitro.Each type of cells was divided into 2 groups ( n=16 each)by a random number table method: RAW264.7 group, RAW264.7 plus MDP group, erbin -/ -RAW264.7 group, and erbin -/ -RAW264.7 plus MDP group.In each MDP group, cells were incubated with 10 μg/ml MDP for 6 h, then immunofluorescence was used to determine the expression of nuclear factor kappa B (NF-κB) p65, and the concentrations of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in the culture medium were determined by enzyme-linked immunosorbent assay. Results:Compared with RAW264.7 group, the concentrations of TNF-α and IL-6 in the culture medium were significantly increased( P<0.05), NF-κB p65 moved to the nucleus, and the red fluorescence area was increased in RAW264.7+ MDP group.Compared with RAW264.7+ MDP group and Erbin -/- RAW264.7 group, the concentrations of TNF-α and IL-6 in the culture medium were significantly increased ( P<0.05), NF-κB p65 moved more markedly to the nucleus, and the red fluorescence area was increased in Erbin -/-RAW264.7+ MDP group. Conclusion:Erbin inhibits MDP-induced inflammatory responses in macrophages through inhibiting the activity of NF-κB p65 in mice.

Diabetes Mellitus and Cause-Specific Mortality: A Population-Based Study

BACKGROUND: To investigate whether diabetes contributes to mortality for major types of diseases. METHODS: Six National Health and Nutrition Examination Survey data cycles (1999 to 2000, 2001 to 2002, 2003 to 2004, 2005 to 2006, 2007 to 2008, and 2009 to 2010) and their linked mortality files were used. A population of 15,513 participants was included according to the availability of diabetes and mortality status. RESULTS: Participants with diabetes tended to have higher all-cause mortality and mortality due to cardiovascular disease, cancer, chronic lower respiratory diseases, cerebrovascular disease, influenza and pneumonia, and kidney disease. Confounder-adjusted Cox proportional hazard models showed that both diagnosed diabetes category (yes or no) and diabetes status (diabetes, prediabetes, or no diabetes) were associated with all-cause mortality and with mortality due to cardiovascular disease, chronic lower respiratory diseases, influenza and pneumonia, and kidney disease. No associations were found for cancer-, accidents-, or Alzheimer's disease-related mortality. CONCLUSION: The current study's findings provide epidemiological evidence that diagnosed diabetes at the baseline is associated with increased mortality risk due to cardiovascular disease, chronic lower respiratory diseases, influenza and pneumonia, and kidney disease, but not with cancer or Alzheimer's disease.

Relationship between cholinergic anti-inflammatory pathway and autophagy during liver injury in septic mice / 中华麻醉学杂志

Objective To evaluate the relationship between cholinergic anti-inflammatory pathway and autophagy during liver injury in septic mice.Methods SPF healthy male 32 C57BL/6 mice,aged 6-8 weeks,weighing 18-22 g,were divided into 4 groups (n=8 each) using a random number table method:sham operation group (group Sham),sepsis group (group Sep),α7nAChR agonist GTS-21 plus sepsis group (GTS-21+Sep group),and α7nACh antagonist α-BGT plus sepsis plus GTS-21 group (α-BGT+Sep+GTS-21 group).Sepsis was induced by cecal ligation and puncture.GTS-21 4 mg/kg was intraperitoneally injected immediately after operation in group GTS-21 +Sep.α-BGT 1 mg/kg was intraperitoneally injected at 15 min before operation,and GTS-21 4 mg/kg was intraperitoneally injected immediately after operation in group α-BGT+Sep+GTS-21.Blood samples were obtained at 6 h after surgery for determination of serum aspartate transaminase (AST) and alanine transaminase (ALT) concentrations by enzyme-linked immunosorbent assay.Liver tissues were obtained for determination of the expression of microtubule-associated protein-1 light chain 3-Ⅱ (LC3 Ⅱ) and sequestosome-1/p62 (by Western blot) and for examination of the number of autophagosomes in liver cells (under a transmission electron microscope).Results Compared with Sham group,the expression of LC3 Ⅱ and sequestosome-1/p62 was significantly up-regulated,the number of autophagosomes was increased,and the serum AST and ALT concentrations were increased in Sep group (P＜0.05).Compared with Sep group,the expression of LC3 Ⅱ was significantly up-regulated,the expression of sequestosome-1/p62 was down-regulated,the number of autophagosomes was increased,and the serum AST and ALT concentrations were decreased in GTS-21 +Sep group (P＜0.05).Compared with GTS-21 +Sep group,the expression of LC3 Ⅱ was significantly down-regulated,the expression of sequestosome-1/p62 was up-regulated,the number of autophagosomes was decreased,and the serum AST and ALT concentrations were increased in α-BGT+Sep+GTS-21 group (P＜0.05).Conclusion Activation of the cholinergic anti-inflammatory pathway can enhance the level of autophagy in liver cells and is involved in the endogenous protective mechanism of sepsis-induced liver injury in septic mice.

The dynamic expr ession and significance of regulatory T cells, T helper cell 17 , interleukin-17 and interleukin-23 in patients with multiple sclerosis / 中华风湿病学杂志

Objective To investigate the levels of T helper cell 17 (Th17), Th17-related cytokines in-terleukin 17 (IL-17) and interleukin 23 (IL-23) and regulatory T cell (Treg) in relapsing remitting multiple sclerosis (RRMS). Methods In a case-control study, plasma was collected from RRMS patients (n=20) and healthy subjects as control group (n=20). The percentages of Th17 and Treg cells and the levels of IL-17 and IL-23 were tested. The levels of Th17, Treg, IL-17 and IL-23 of the two groups were compared. Patients were treated with methylprednisolone. The levels of Th17, Treg, IL-17 and IL-23 of multiple sclerosis (MS) patients b efore and after treatment were compared. Expanded disability status scale (EDSS) score and the number of Gd-enhancing lesions were evaluated in the case group. Statistical analysis was made by body mass index (IBM) statistical program for social sciences (SPSS) 17.0 software. Independent sample t test was conducted to compare the measurement data of the case group and the healthy control group, and enumeration data were compared by χ2 test; paired sample t test was performed to compare the data of the case group before and after treatment; Pearson correlation analysis was made forthe variables of the MS group before treatment. Results In the RRMS group, the percentage of Th17 cells in peripheral blood was significantly higher than the control group [(2.10±0.45)％vs (1.09±0.20)％](t=9.130, P<0.01), the levels of Th17-related cytokines IL-17 and IL-23 were remarkably higher than the control group (IL-17:t=19.843, P<0.01;IL-23:t=22.747, P<0.01), and the percentage of Treg cells was significantly lower than the control group [(1.33 ±0.30)％vs (2.52±0.30)％], (t=12.422, P<0.01). The levels of Th17 and IL-17 were positively associated with EDSS score (Th17: r=0.458, P<0.05; IL-17: r=0.480, P<0.05), there was no significant-correlation between the level of IL-23 and EDSS score (r=0.368, P>0.05), and Th17, IL-17 and IL-23 were positively correlated with the number of Gd-enhancing lesions (Th17: r=0.446, P<0.05; IL-17: r=0.544, P<0.05; IL-23: r=0.461, P<0.05). The levels of Th17, IL-17 and IL-23 in the RRMS group after the treatment with methylprednisolone were obviously decreased than before treatment (Th17: t=5.747, P<0.01; IL-17: t=9.967, P<0.01; IL-23: t=14.697, P<0.01), while that of Treg was apparently increased (t=10.050, P<0.01). Compared with the control group, the levels of Th17, IL-17 and IL-23 in the RRMS group after treatment were higher (Th17: t=6.889, P<0.01;IL-17:t=7.185, P<0.01;IL-23:t=13.284, P<0.01), and the percentage of Treg was lower (t=7.622, P<0.01). EDSS score of the RRMS group after treatment was remarkably decreased than before treatment(t=6.190, P<0.01), but the number of Gd-enhanced lesions after treatment was no significantiy changed (t=1.453, P>0.05). Conclusion Th17/Treg expression imbalance and Th17-related cytokines IL-17, IL-23 may participate in the pathological process of MS, and they might be therapeutic target for MS.

Effect of irisin preconditioning on global cerebral ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective@#To evaluate the effect of irisin preconditioning on global cerebral ischemia-reperfusion (I/R) injury in rats.@*Methods@#Thirty-six healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 3 groups (n=12 each) using a random number table method: sham operation group (group S), global cerebral I/R group (group I/R) and irisin preconditioning group (group I). Global cerebral I/R was induced by occlusion of bilateral common carotid arteries combined with hypotension (MAP maintained at 35-45 mmHg) in anesthetized rats.At 30 min before ischemia, irisin 10 μg/kg (diluted to 10 μg/ml in normal saline) was intravenously injected in group I, and the equal volume of normal saline was intravenously injected in S and I/R groups.Morris water maze test was performed at day 3 of reperfusion to assess the cognitive function.Rats were sacrificed after the end of morris water maze test, and brains were removed for determination of histopathologic changes in hippocampal CA1 region (using HE staining), neuronal apoptosis in hippocampal CA1 region (Tunel staining), glial fibrillary acidic protein (GFAP) expression (by Western blot), myeloperoxidase (MPO) activity in the hippocampal tissues (by colorimetric assay), and contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in hippocampal tissues (by enzyme-linked immunosorbent assay). The cell necrosis rate and apoptotic rate were calculated.@*Results@#Compared with group S, the escape latency was significantly prolonged on 1-5 days in group I/R and on 1-3 days in group I, the time of staying at 1st quadrant was significantly shortened, the cell necrosis rate and apoptotic rate were increased, the expression of GFAP was up-regulated, and the activity of MPO and contents of TNF-α and IL-1β were increased in I/R and I groups (P<0.05 or 0.01). Compared with group I/R, the escape latency was significantly shortened on 1-5 days, the time of staying at 1st quadrant was prolonged, the cell necrosis rate and apoptotic rate were decreased, the expression of GFAP was down-regulated, and the MPO activity and contents of TNF-α and IL-1β were decreased in group I (P<0.05 or 0.01).@*Conclusion@#Irisin preconditioning can reduce the global cerebral I/R injury in rats, and the mechanism may be related to inhibiting activation of astrocytes in hippocampus and reducing inflammatory responses.

Anatomic basis and clinical application of periorbital flap pedicled with zygomatic orbital artery / 中华整形外科杂志

Objective@#To explore the clinical application effect of the orbital periorbital perforator flap pedicled with zygomatic artery to repair the defect of eyelid ectropion and the defect after tumor resection.@*Methods@#(1)Perfused 10 fresh cadavers gelatin lead oxidate with one-time arteriography and CT spiral scanning, and imported DICOM data into Mimics 17.0 for rapid body mapping and three-dimensional reconstruction, and observed the source of zygomatic orbital artery and distribution rules of perforating branches. (2)From July 2012 to July 2017, 18 clinical cases were repaired by orbital periorbital perforator flap pedicled with zygomatic artery, the flap was cut with the same width as the defect width, and the length of the flap was 2 to 3 times the defect length, with an area of 0.3 cm × 1.5 cm to 2.0 cm × 3.0 cm.@*Results@#The zygomatic orbital artery originated from the superficial temporal artery, extending up to about the midpoint of the line between the anterior ear and the lateral canthus.The clinical application of the orbital periorbital flap with the perforating branch of the zygomatic orbital artery in 18 cases survived and healed well. After 1 month to 2 years of follow-up, the color, texture and shape function recovered well.@*Conclusions@#The orbital periorbital flap with the perforating branch of the zygomatic orbital artery is a good method for reconstruction of ectropion and palpebral defect due to its reliable movement and the arterial arch connected with the orbicularis suborbicularis.

Effect of irisin preconditioning on global cerebral ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective To evaluate the effect of irisin preconditioning on global cerebral ischemiareperfusion (I/R) injury in rats.Methods Thirty-six healthy male Sprague-Dawley rats,aged 8-10 weeks,weighing 250-300 g,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),global cerebral I/R group (group I/R) and irisin preconditioning group (group I).Global cerebral I/R was induced by occlusion of bilateral common carotid arteries combined with hypotension (MAP maintained at 35-45 mmHg) in anesthetized rats.At 30 min before ischemia,irisin 10 μg/kg (diluted to 10 μg/ml in normal saline) was intravenously injected in group I,and the equal volume of normal saline was intravenously injected in S and I/R groups.Morris water maze test was performed at day 3 of reperfusion to assess the cognitive function.Rats were sacrificed after the end of morris water maze test,and brains were removed for determination of histopathologic changes in hippocampal CA1 region (using HE staining),neuronal apoptosis in hippocampal CA1 region (Tunel staining),glial fibrillary acidic protein (GFAP) expression (by Western blot),myeloperoxidase (MPO) activity in the hippocampal tissues (by colorimetric assay),and contents of tumor necrosis factor-alpha (TNF-cα) and interleukin-1 beta (IL-1β) in hippocampal tissues (by enzyme-linked immunosorbent assay).The cell necrosis rate and apoptotic rate were calculated.Results Compared with group S,the escape latency was significantly prolonged on 1-5 days in group I/R and on 1-3 days in group I,the time of staying at 1st quadrant was significantly shortened,the cell necrosis rate and apoptotic rate were increased,the expression of GFAP was up-regulated,and the activity of MPO and contents of TNF-α and IL-1β were increased in I/R and I groups (P＜0.05 or 0.01).Compared with group I/R,the escape latency was significantly shortened on 1-5 days,the time of staying at 1st quadrant was prolonged,the cell necrosis rate and apoptotic rate were decreased,the expression of GFAP was down-regulated,and the MPO activity and contents of TNF-α and IL-1β were decreased in group I (P＜0.05 or 0.01).Conclusion Irisin preconditioning can reduce the global cerebral I/R injury in rats,and the mechanism may be related to inhibiting activation of astrocytes in hippocampus and reducing inflammatory responses.

Effect of percutaneous coronary intervention and medical therapy on quality of life and cognitive function in patients with coronary heart disease / 中南大学学报(医学版)

Objective:To explore the effect and difference of percutaneous coronary intervention (PCI) and medical therapy on quality of life and cognitive function in patients with coronary heart disease (CHD),and to investigate the relationship between quality of life and cognitive function.Methods:A total of 320 patients with CHD,who underwent coronary angiography and PCI (PCI group,n=160),or underwent coronary angiography and medical therapy (drug therapy group,n=160),were selected.The quality of life was assessed by using the Health Survey Form SF-36 (SF-36) and the Seattle Angina Questionnaire (SAQ),and the cognitive function was assessed by using the Mini-Mental State Examination (MMSE).General data of patients were collected on the day of coronary angiography.Telephone follow-up was conducted in 1 month after treatment,and the outpatient review was carried out in 3 and 6 months after treatment.Results:A total of 309 valid questionnaires were collected.The scores of quality of life in the PCI group and the drug therapy group after treatment were both increased compared with those before treatment (both P＜0.05).The SF-36 scores of four dimensions (role physical,bodily pain,vitality and mental health) in the PCI group were all significantly greater than those in the drug therapy group (all P＜0.05).The SAQscores of two dimensions (angina stability and angina frequency) were both higher in the PCI group than those in the drug therapy group in 6 months of post-operation (all P＜0.05).There was no significant difference in cognitive function before and after the treatment in the 2 groups (P＞0.05).There was no significant difference in cognitive function between the PCI group and the drug therapy group (P＞0.05).In the PCI group,physical function,role physical,bodily pain,and role emotional were positively correlated with cognitive function (r=0.207,0.182,0.184,0.176 respectively,all P＜0.05).In the drug therapy group,there was no correlation between quality of life and cognitive function.Conclusion:The quality of life for the patients is improved in the PCI group and the drug therapy group,but the improvement degree in the PCI group is more obvious.Both PCI and drug therapy do not result in the decrease of cognitive function,and there is no difference between the 2 groups.There is positive correlation between quality of life and cognitive function in the PCI group,there is no correlation between quality of life and cognitive function in the drug therapy group.

Levels of peripheral T helper17 cells and serum T helper17-related cytokines in patients with multiple sclerosis: a Meta-analysis / 中华风湿病学杂志

Objective To test whether T helper 17 (Th17) cells was involved in the pathogenesis of multiple sclerosis (MS) by conducting a meta-analysis of the researches documenting the levels of Th17 cells and Th17-related cytokines [interleukin (IL)-17,IL-23] in patients with MS.Methods We identified articles reporting proportion of Th17 cells and the serum levels of IL-17,IL-23 in MS patients by searching CNKI,Wanfang med online,Embase,PubMed,Cochrane,WebofKnowledge,Food and Drug Administration (FDA).gov,and ClinicalTrials.gov.We registered this study at the International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42017059113).The evidence level of selected studies was identified by guidelines from the Oxford Center for Evidence-Based Medicine 2011.We employed the Newcastle-Ottawa Quality Assessment Scale (Case Control Studies) to perform the included resear.Stata 12.0 was adopted for processing Meta-analysis of the data by using a random effects model.Results A total 16 researches were included in our Meta-analysis from 587 identified studies.The proportion of Th17 cells [1.89％(1.10％,2.69％),P＜0.01] and the levels of serum IL-17 [2.77(1.77,3.77) pg/ml,P＜0.01] and IL-23 [2.96(1.51,4.40)pg/ml,P＜0.01] increased dramatically in MS individuals compared with control subjects.Conclusion The results of this Meta-analysis has demonstrated that MS patients have a higher proportion of Th 17 cells in higher levels of serum IL-17 and IL-23 compared to control subjects,which has demonstrated that Th17 cells may play an vital role in the pathogenesis process of MS patients.