Taking the mechanism of glucose catabolism disorder in depression as an example to explore the research ideas and strategies of stable isotope tracer metabolomics / 药学学报

Stable isotope tracer metabolomics tracks and analyzes the whole metabolic process of the body through the tracer atoms, which belongs to the frontier technology in the field of biomedicine. This technology is of great significance and value for explaining the pathogenesis of diseases, finding biomarkers of diseases and drug action targets. Taking the mechanism of glucose catabolism disorder in depression as an example, this paper systematically expounds the stable isotope tracer metabolomics technology and its application. The research idea of stable isotope tracer metabolomics based on unmarked metabolomics was put forward, and the research strategy of biological significance interpretation from four dimensions of metabolite isotope abundance, key metabolic enzymes, metabolic flow direction and metabolite flow was given, which broke through the bottleneck of stable isotope tracer metabolomics research technology based on overall animal experiment, and provided scientific basis for the promotion and application of this technology.

Research progress of gut microbiota in the antidepressant effect of traditional Chinese medicine / 药学学报

Depression is a common emotional mental disorder. Patients not only continuously showed depression, pessimism and apathy in mood, but also have gastrointestinal symptoms such as anorexia and constipation in body. Widely attention has been also received in the potential biological role of gut microbiota in the pathogenesis of depression. It plays an important role in the interaction between the intestine and the brain, not only affecting the intestinal barrier function, but also maintaining the homeostasis of host through the microbiota-gut-brain axis. In recent years, the traditional Chinese medicine (TCM) has the advantages of obvious therapeutic effects and few side effects when treating neuropsychiatric diseases, such as depression. The pharmacological mechanism of TCM exerting antidepressant effects by regulating the structure of gut microbiota, reducing displacement, and maintaining the normal function of gut microbiota has been also widely concerned. By investigating the relevant literature in recent years, this paper summarizes the antidepressant effect of TCM in different directions such as Chinese medicine monomer, single medicine and compound medicine. And this paper reviews the antidepressant effects and mechanisms of TCM at different levels, such as the correction of gut microbiota structure, the regulation of immunity, the transplantation of gut microbiota and the regulation of its metabolites. This paper will provide a basis for further explaining the mechanism of gut microbiota in depression and the mechanism of antidepressant effect of TCM.

Long-term outcomes of posterior release and reduction for irreducible atlantoaxial dislocation / 中华骨科杂志

Objective:To evaluate the long-term outcomes of posterior release, reduction, fixation, and fusion for irreducible atlantoaxial dislocation (AAD).Methods:Between January 2005 and June 2016, a total of 31 patients with irreducible AAD who had received posterior approach surgery were included. Among them, there were 13 males and 18 females, the average age was 39.1±13.5 years (range 9-72 years). The clinical data of the eligible individuals were collected and analyzed. Neck disability index (NDI) and Japanese Orthopaedic Association (JOA) scores were recorded to evaluate the recovery of neck and neurological functions. The atlantodental interval (ADI), clivus-canal angle (CCA), and cervico-medullary angle (CMA) were measured to evaluate the reduction of AAD. C 0-C 2 angle and C 2-C 7 angle were measured to evaluate the recovery of cervical alignment. For individuals with basilar invagination, the distances from the tip of odontoid process to Chamberlain line and Wackenheim line were measured to assess the reduction in the vertical direction. The duration of bony fusion and complications were also analyzed. Results:The mean follow-up period was 82.7±26.4 months (range 61-170 months). In terms of functional scores, the NDI dropped from 43.41%±11.60% before surgery to 12.19%±6.97% at the six months follow-up, and 9.45%±7.51% at the last follow-up ( F=89.56, P<0.001). The JOA increased from 9.48±2.41 points before surgery to 14.71±1.42 points at the six months follow-up, and 14.97±1.47 points at the last follow-up ( F=52.89, P<0.001). Regarding the horizontal and vertical dislocations, the ADI decreased from 9.16±2.32 mm before surgery to 1.39±1.04 mm at the six months follow-up, and 1.29±1.08 mm at the last follow-up ( F=189.61, P<0.001). The distance from the tip of odontoid process to Chamberlain line decreased from 11.15±4.35 mm before surgery to 2.03±2.83 mm at the six months follow-up, and 2.15±3.02 mm at the last follow-up ( F=37.58, P<0.001). The distance from the tip of odontoid process to Wackenheim line reduced from 6.81±2.57 mm before surgery to -2.23±1.58 mm at the six months follow-up, and -2.27±1.58 mm at the last follow-up ( F=122.16, P<0.001). For the amelioration of the compression on medulla and spinal cord, the CCA increased from 113.68°±12.67° before surgery to 143.39°±7.38° at the six months follow-up, and 142.39°±7.13° at the last follow-up ( F=67.13, P<0.001). The CMA increased from 115.71°±13.69° before operation to 145.58°±10.78° at the last follow-up ( F=41.44, P<0.001). Regarding the curvature of the cervical spine, the C 0-C 2 angle recovered from 1.94°±15.82° before surgery to 14.84°±6.45° at the last follow-up ( F=11.97, P<0.001), and the C 2-C 7 angle ameliorated from 27.26°±8.49° before operation to 19.26°±5.44° at the last follow-up ( F=11.13, P<0.001). Bony fusion was achieved in all cases, the fusion time was 9.71±2.55 months (range 5-15 months). A total of five complications occurred in the cases (two cerebrospinal fluid leakages, one deep infection, one transient neurologic deficit, and one dysphagia). They were all cured with corresponding treatments. In the last follow-up, none of the cases developed failure of internal fixation or re-dislocation. Conclusion:Posterior approach release, reduction, fixation and fusion technique is a safe and efficient surgical strategy with favorable long-term follow-up outcomes for irreducible AAD.

Research progress of metabolic flux analysis technology in glucose metabolism pathway research / 药学学报

With the wide application of stable isotope tracer metabolomics technology, its comprehensive analysis and in-depth mining of data are particularly important, and metabolic flux analysis is one of the main technical means, especially in the study of glucose metabolism. Metabolic flux analysis technology combines isotope tracing with mathematical models to deduce and calculate the metabolic flux between metabolites. The metabolic flux provides more information for research and reflects a dynamic metabolic process more clearly and specifically. This paper reviews the basic process, precautions, and application examples of metabolic flux analysis in glucose metabolism research, and provides a reference for the application of metabolic flux analysis based on stable isotope tracer metabolomics in glucose metabolism research.

Analysis of the equity of health human resource allocation for echinococcosis control based on Gini index / 中国血吸虫病防治杂志

OBJECTIVE@#To analyze the current status and evaluate the equity of health human resource allocation for echinococcosis control in Ganzi Tibetan Autonomous Prefecture, Sichuan Province, so as to provide the empirical evidence for optimizing the health human resource allocation for echinococcosis control.@*METHODS@#A questionnaire survey was performed to collect the numbers of health human sources for echinococcosis control, including health workers, healthcare professionals, certified/assistant physicians and registered nurses, per 1 000 permanent residents, per 1 000 m2, per 1 000 residents screened using Bmode ultrasonography and per 1 000 echinococcosis patients in two highly endemic counties and three lowly endemic counties in Ganzi Tibetan Autonomous Prefecture, Sichuan Province from 2016 to 2019. The equity of health human resource allocation for echinococcosis control was evaluated by permanent residents and geographical areas using Lorenz curve and Gini index in Ganzi Tibetan Autonomous Prefecture from 2016 to 2019.@*RESULTS@#The numbers of health workers, healthcare professionals, certified/assistant physicians and registered nurses per 1 000 permanent residents, per 1 000 permanent residents, per 1 000 m2, per 1 000 residents screened using B-mode ultrasonography and per 1 000 echinococcosis patients were 0.99-, 1.06-, 1.78- and 1.88-fold; 3.38-, 3.67-, 6.00- and 6.00-fold; 1.64-, 1.74-, 3.22- and 3.18-fold; and 64.92-, 70.39-, 139.34- and 117.44-fold more in lowly endemic counties than in highly endemic countries in Ganzi Tibetan Autonomous Prefecture, Sichuan Province, 2019. The Gini indexes of health human resource allocation for echinococcosis control were 0.371 to 0.397 by permanent residents and 0.477 to 0.591 by geographical areas in Ganzi Tibetan Autonomous Prefecture from 2016 to 2019, and the Gini indexes (0.469 to 0.730) for allocation of certified/assistant physicians and registered nurses were both higher than those of health workers and healthcare professionals (0.302 to 0.451) by both permanent residents and geographical areas.@*CONCLUSIONS@#The health human resource allocation for echinococcosis control showed general equity by permanent residents and poor equity by geographical areas in Ganzi Tibetan Autonomous Prefecture, Sichuan Province from 2016 to 2019.

Genomic and transcriptomic analysis unveils population evolution and development of pesticide resistance in fall armyworm Spodoptera frugiperda

The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.

Based on plasma metabonomics and network analysis to research the mechanisms of Chaigui granules for treating depression / 药学学报

The purpose of this study was to systematically analyze the antidepressant mechanism of Chaigui granules from the perspective of biological metabolic network by using integrated metabolomics and biological network analysis tools. The model of chronic unpredictable mild stress (CUMS) depression rat was established, and LC-MS-based plasma metabolomics was used to identify the key metabolites and analyze metabolic pathways underlying the antidepressant effects of Chaigui Granules. The key metabolites regulated by Chaigui granules was integrated with biological network analysis tools to further focus on the key metabolic pathways and explore the potential targets of the antidepressant effect of Chaigui granules. The results showed that there were significant differences in the plasma levels of 20 metabolites in the model group compared with the control group (P < 0.05), Chaigui granules significantly regulated 12 metabolites including docosatrienoic acid, 3-hydroxybutyric acid, 4-hydroxybenzaldehyde, chenodeoxycholic acid, cholic acid, L-glutamine, glycocholic acid, linoleyl carnitine, L-tyrosine, N-acetylvaline, palmitoylcarnitine, arachidonic acid. Further network analysis of the key metabolites regulated by Chaigui granules indicated that plasma arachidonic acid metabolism might be the core pathway for the antidepressant effect of Chaigui granules, with 10 proteins were potential targets for the antidepressant effect of Chaigui granules, including CYP2B6, CYP2E1, CYP2C9, CYP2C8, PLA2G6, PTGS2, ALOX15B, PTGS1, ALOX12 and ALOX5. The animal experimental operations involved in this paper was followed the regulations of the Animal Ethics Committee of Shanxi University and passed the animal experimental ethical review (Approval No. SXULL2020028).

Application of stable isotope-resolved metabolomics in glucose catabolism / 药学学报

With the rapid development of high sensitivity detection techniques such as nuclear magnetic resonance and mass spectrometry, stable isotope-resolved metabolomics has been widely used in elucidating the regulatory mechanism of metabolic pathways and metabolic flow analysis, and some breakthroughs have been made. In this paper the application of stable isotope-resolved metabolomics in glucose catabolic regulation, metabolic flow analysis and functional interpretation of key metabolic pathways is reviewed, providing references for the wider use and application of this technology.

Application progress of experimental animal model of humanized fecal microbiota transplantation in depression research / 药学学报

The incidence rate of depression is increasing, but its pathological mechanism is still unknown. More evidence shows that the occurrence and development of depression is closely related to the changes of gut microbiome. However, due to the huge differences in bacterial composition among individuals caused by different environmental factors, researchers usually need a large number of samples to get reliable results. Experimental animal models play an important role in the pathogenesis of diseases and the mechanism of drug action because of their highly consistent background, controllable experimental environment, and the characteristics of artificial intervention. Therefore, the selection of appropriate experimental animal models can not only simulate the clinical symptoms of human depression, but also reveal the causal relationship between clinical characteristics and gut microbiome changes. In this review, the development and application of fecal microbiota transplantation technology, the close relationship between flora and depression, the application of humanized fecal microbiota transplantation experimental animal model in the study of depression, as well as the preparation methods and key technologies of humanized fecal microbiota were summarized, which provided a reference for the research on the pathogenesis of depression and the mechanism of antidepressant drugs of humanized fecal microbiota transplantation experimental animal model. This review provides a reference for the reasonable application of this aspect.

Effects of XELOX regimen and FOLFOX4 regimen on colon cancer and their influences on serum tumor markers and cytological indicators / 肿瘤研究与临床

Objective:To compare the effects of XELOX (oxaliplatin + capectabine) regimen and FOLFOX4 (oxaliplatin + calcium leucovorin + fluorouracil) regimen on colon cancer and their influences on serum tumor markers and cytological indexes.Methods:A total of 84 patients with colon cancer treated in Wuhu Hospital of Chinese Medicine of Anhui Province from January 2016 to January 2019 were selected, and the patients were randomly divided into the observation group (XELOX regimen, 42 cases) and the control group (FOLFOX4 regimen, 42 cases) according to the random number table. The efficacy, side effects, the changes of cytological indicators and serum tumor markers before and after chemotherapy between the two groups were compared.Results:The short-term effective rate was 76.19% (32/42) in the observation group and 61.91% (26/42) in the control group, and the difference was not statistically significant (χ 2 = 2.005, P=0.156). The incidence of side effects in the observation group was lower than that in the control group [35.71% (15/42) vs. 59.53% (25/42), χ 2 = 4.773, P = 0.029]. There was no significant difference in the levels of carbohydrate antigen 199 (CA19-9), colon cancer-specific antigen (CCSA-2) and osteopontine (OPN) between the two groups before treatment (all P > 0.05); after treatment, CA19-9, CCSA-2, OPN levels were lower than those before treatment of the two groups (all P < 0.05); after treatment, CA19-9, CCSA-2, OPN levels in the observation group were lower than those in the control group (all P < 0.05). Before treatment, there was no significant difference in the levels of neutrophils to lymphocytes ratio (NLR), platelet-lymphocytes ratio (PLR), and red cell distribution width (RDW) between the two groups (all P > 0.05); the levels of NLR, PLR and RDW after treatment in the two groups were decreased compared with those before treatment (all P < 0.05); NLR, PLR and RDW levels in the observation group after treatment were lower than those in the control group (all P < 0.05). In the observation group, the recurrence rate of 1-year, 2-year, 3-year was 4.76% (2/42), 14.26% (6/42), and 19.05% (8/42), respectively; in the control group, the recurrence rate of 1-year, 2-year, 3-year was 11.90% (5/42), 21.43% (9/42), and 26.19% (11/42), respectively; there was no statistical difference between the two groups (all P > 0.05); in the observation group, the survival rate of 1-year, 2-year, 3-year was 92.86% (39/42), 78.57% (33/42), and 71.43% (30/42), respectively; in the control group, the survival rate of 1-year, 2-year, 3-year was 85.71% (36/42), 69.05% (29/42), and 64.28% (27/42), and there was no statistically significant difference between the two groups (all P > 0.05). Conclusions:XELOX regimen and FOLFOX regimen have similar short-term and long-term effects on patients with colon cancer. They both can decrease the levels of serum tumor markers and cytological indicators of patients, and improve their prognosis, while XELOX regimen has low side effects.

Metabolic module identification and biological mechanism of Xiaoyaosan for treatment of depression / 药学学报

The antidepressant effect of Xiaoyaosan has been demonstrated. It is of value to explore the biological mechanism of Xiaoyaosan in the treatment of depression from the perspective of functional modules by using the method of functional module division of the metabolic network. The differential metabolites and related enzymes and proteins regulated by Xiaoyaosan were identified in the database. Pathway enrichment analysis and crosstalk pathway analysis of Xiaoyaosan regulated metabolites was carried out. A network of differentially regulated metabolites and their enzymes and proteins was constructed by using the STRING tool. The CNM decomposition algorithm was used to extract the functional modules of the network and enrichment analysis of functional modules was carried out. The results show that Xiaoyaosan regulates 97 differential metabolites, 234 related enzymes and 258 depression-related proteins. The pathways crosstalk analysis was divided into two sub-networks, one of which is related to the neural system and cell signal transduction, the other is related to the endocrine system and metabolic pathways. KEGG pathway enrichment analysis of the network and 9 functional modules extracted by the CNM algorithm shows that module 1 and module 3 belong to the pathways that can be enriched into more pathways with fewer proteins. The corresponding functions of these pathways include the endocrine system, amino acid metabolism, the nervous system and signal transduction. In this study, pathway crosstalk analysis and metabolic network module division strategies were used to explain the biological mechanism of Xiaoyaosan in the treatment of depression, providing ideas and methods for in-depth study of the pharmacological mechanism of this traditional Chinese medicine from the perspective of metabolic regulation.

Pharmacokinetic/pharmacodynamic modeling of the antitumor action of bispecific CD3/EpCAM antibody M701 in human colorectal cancer xenograft mice / 药学学报

M701 is a bispecific CD3/EpCAM T-cell engager antibody for the treatment of malignant ascites. We developed a population pharmacokinetic/pharmacodynamic (PK/PD) model to quantitatively describe and predict the antitumor effect of M701 in human colorectal cancer xenograft mice. We developed the M701 PK model based on plasma concentration data after i.v. administration. A tumor growth model for human colorectal cancer xenograft was developed to evaluate the antitumor effect of M701. We additionally simulated the inhibitory effect of M701 on tumor volume under different dose regimens based on a PK/PD model. A two-compartment model was developed to predict the PK in human colorectal cancer xenograft mice. The relationship between the M701 concentration and tumor growth inhibition was characterized by a combined Simeoni tumor growth/transit compartment model. The estimated pharmacodynamic parameters were related to the tumor growth characteristics λ0 (0.212 d-1) and λ1 (0.044 7 cm3·d-1), to the drug potency k2 (0.071 5 mL·ng-1·d-1), and to the kinetics of tumor cell death k1 (2×10-5 d-1). A model visual predictive check showed that both the PK model and the tumor growth model closely fit the observed data. Simulated tumor growth after administration of M701 (0.5 mg·kg-1 every 6 days and 0.25 mg·kg-1 every 3 days) could be effectively inhibited. This population PK/PD model of M701 provides insight into the antitumor effect of M701 and supports the further therapeutic development of M701.

Lignans with NO inhibitory activity from Tinospora sinensis / 中国天然药物

Two new lignan glucosides, tinsinlignans A and B (1 and 2), two new oxyneolignans, tinsinlignans C and D (3 and 4), along with one known analogue (5), were isolated from the stems of Tinospora sinensis. The structures of the new compounds were elucidated based on analysis of spectroscopic data, and the absolute configuration of 1 was determined through electronic circular dichroism (ECD) calculation based on the time-dependent density functional theory (TD-DFT). Compounds 1-4 were evaluated for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells and compounds 1 and 2 exhibited moderate inhibitory activities with IC

Lipid Accumulation and IL-6 Production in L02 Hepatocytes Induced by Sodium Oleate: Dose and Time Dependence / 生物医学与环境科学（英文）

To explore interleukin-6 (IL-6) production and characterize lipid accumulation in L02 hepatocytes induced by sodium oleate. L02 hepatocytes were incubated with 0, 37.5, 75, 150, 300, 600, or 1,200 μmol/L sodium oleate for 24 h, and the supernatant was collected to detect the concentration of IL-6. L02 hepatocytes were incubated with 300, 150, 75, or 0 μmol/L sodium oleate for 0-24 h. The supernatant was collected for detection of IL-6 and free fatty acids. L02 hepatocytes treated with 300 μmol/L sodium oleate for 0-24 h were stained with Oil Red O. With extended sodium oleate incubation time, IL-6 levels increased, and free fatty acids decreased. After 24 h incubation, IL-6 levels increased as sodium oleate increased from 37.5 to 300 μmol/L (

Pathogenesis of chronic social defeat stress model induced depressive-like mouse model according to LC-MS/MS-based metabolomics / 中国药理学与毒理学杂志

OBJECTIVE To explore the pathogenesis of depression according to the LC-MS/MS-based metabolo?mics in the mouse model which exhibits social avoidance state induced by the chronic social defeat stress model (CSDS). METHODS Twenty male C57BL/6N mice were randomly divided into control group and model group suffering CSDS, and the ICR retired breeder mice were used to attack the model group for 14 d of chronic social defeated stress. The open field test and source preference test were both used to observe depression-like behavior. Besides, the social inter?action test is used to observe the social interaction state, especially. After the stress, the serum samples of mice were collected, and the changes of endogenous metabolites were analyzed by LC-MS metabolomics technology, and the pathway analysis of the differential metabolites was performed to explore the pathogenesis of the CSDS induced depres?sive-like mouse model. RESULTS After the stress of CSDS was completed, the mice in the model group showed a significant slowdown in body weight growth, a reduction in the source preference rate, and a significant reduction in the total distance and the number of rearing in the open field test. Distinctively, the social interaction rate is remarkably decreasing. There are 24 differential metabolites found in the serum of CSDS model mice. CONCLUSION The mouse who suffered CSDS stress would show depressive-like behavior. Based on the LC-MS/MS metabolomics, 24 differential metabolites were found in the serum of CSDS model mice. The amino acid metabolism might be significant to the patho?genesis of the CSDS induced depressive-like mouse model.

Effects of Electroacupuncture on Learning-memory and P35/P25-Cyclin-dependent Kinase 5-Tau Phosphorylation Signal Pathway in Prefrontal Cortex of Rats with Alzheimer's Disease / 中国康复理论与实践

Objective:To observe the effect of electroacupuncture at Baihui (DU20) and Shenshu (BL23) acupoints on learning-memory ability and expression of the relative protein of P35/P25-cyclin-dependent kinase 5 (CDK5)-Tau phosphorylation signaling pathway in the prefrontal cortex (PFC) in rats with Alzheimer's disease (AD), so as to reveal its potential mechanisms in treating AD. Methods:Male adult Sprague-Dawley rats were randomly divided into normal control group, sham group, model group and treatment group with six rats in each group. The AD model was constructed by bilateral hippocampal injection of Aβ25-35 in latter two groups. Equal amount of normal saline was injected into the sham group. The treatment group was acupunctured at Baihui and Shenshu once a day for ten days. All the rats were tested with Morris Water Maze. Immunohistochemistry staining and Western blotting were used to detect the related protein of P35/P25-CDK5-Tau protein phosphorylation in the PFC. Results:Compared with the normal control group and the sham group, the escape latency and escape length increased (P < 0.05) and the times crossing the platform reduced (P < 0.05) in the model group; compared with the model group, the escape latency and escape length reduced (P < 0.05), and the times crossing the platform increased (P < 0.05) in the treatment group. The optical density of P35/P25 and CDK5 were significantly higher in the model group than in the normal control group and the sham group (P < 0.01), and they were lower in the treatment group than in the model group (P < 0.001). The relative expression of P35/P25, CDK5, Tau[pS199] and Tau[pS202] were higher in the model group than in the normal control group and the sham group (P < 0.05), and the expression of the above proteins was lower in the treatment group than in the model group (P < 0.05). Conclusion:Electroacupuncture could improve the learning-memory and spatial exploration ability, which associate with inhabiting the P35/P25-CDK5-Tau protein phosphorylation signaling pathway in the PFC to delay the development of AD.

Effect of Electroacupuncture on Expression of Phosphatidylinositol 3 Kinase/Glycogen Synthase Kinase 3 Alpha Pathway Related Proteins and Senile Plaque Deposition in Cortex of APP/PS1 Mice / 中国康复理论与实践

Objective:To observe the effects of electroacupuncture (EA) on expression of phosphatidylinositol 3 kinase/glycogen synthase kinase 3 alpha (PI3K/GSK3α) signaling pathway related proteins in cortex of APP/PS1 double transgenic mice, and the senile plaque (SP) deposit. Methods:Three-month-old male APP/PS1 mice were randomly divided into model group (n = 6) and EA group (n = 6) after gene identification, and other six wild C57 mice were as control group. EA group accepted EA at Baihui (GV20) and bilateral Shenshu (BL23) for 14 days. Then, the amount of SP in cortex, the expression of P85α and P110α, subunits of PI3K, and GSK3α and pS21-GSK3α, were detected with Western blotting and immunohistochemistry. Results:The SP increased in the model group compared with that of the control group (P < 0.001), and it decreased in EA group compared with that of the model group (P < 0.001). All the proteins expressed in the cytoplasm of cortical neurons. The expression of pS21-GSK3α, P110α and P85α decreased in the model group compared with that of the control group (P < 0.01), while the expression of GSK3α increased (P < 0.05). The expression of pS21-GSK3α, P110α and P85α increased in EA group compared with that of the model group (P < 0.01), while the expression of GSK3α decreased (P < 0.05). Conclusion:EA may adjust the PI3K/GSK3α signaling pathway, to reduce the formation and deposition of SP in APP/PS1 double-transgenic mice.

Comparison of efficacy between anterior and posterior combined approach and posterior reduction alone in the treatment of basilar invagination with irreducible atlantoaxial dislocation / 中华骨科杂志

Objective:To compare the clinical efficacy and complications of combined anterior and posterior approach and simple posterior release reduction and internal fixation in the treatment of basilar invagination (BI) with irreducible atlantoaxial dislocation (IAAD) .Methods:The medical records of 47 patients with basilar invaginationdepression complicated with refractory atlantoaxial dislocation who received surgical treatment from July 2000 to December 2017 were retrospectively analyzed. The patients were divided into anterior and posterior combined approach group (23 cases) and posterior approach group (24 cases). Key observation indicators include: Chamberlain line (CL), Wackenheim line (WL), McGae line (ML), atlantodens interval (ADI), cervicomedullary angle (CMA), clivus-canal angle (CCA), JOA scores (Japanese Orthopedic Association, JOA) and Ranawat grade.Results:The average follow-up was 48.7±31.2 months in the A-P group and 44.4±33.4 months in the P group. The average preoperative JOA score of the A-P group was 8.20±2.75 points and 14.98±1.05 points at the last follow-up, and the improvement rate was 77.35%±11.35%. The average preoperative JOA score of the P group was 8.06±2.52 points, and the last follow-up was 14.71±0.62 points, and the improvement rate was 74.38%±10.52%. There was no statistically significant difference between the two groups in JOA score ( t=0.877, P=0.262) and improvement rate ( t=1.478, P=0.206) at the last follow-up. The preoperative CL, WL, ML, ADI, CMA and CCA angles of the A-P group were 13.12±5.76 mm, 6.94±3.55 mm, 7.04±4.57 mm, 9.75±2.06 mm, 110.85°±13.6°, 95.32°±18.3°, respectively. The last follow-up was 1.68±2.53 mm, -2.76±2.26 mm,-1.52±2.43 mm, 1.12±1.55 mm, 149.26°±12.6°, and 141.42°±13.7°, respectively, with statistically significant differences from preoperative. The preoperative CL, WL, ML, ADI, CMA and CCA angles of P group were 12.52±5.17 mm, 6.59±3.04 mm, 6.94±4.32 mm, 9.88±1.93 mm, 115.35°±12.4°, 97.25°±16.4°, respectively. The results of the last follow-up were 2.00±3.67 mm, -3.06±1.85 mm, -1.76±2.88 mm, 1.17±1.18 mm, 146.76°±11.4° and 137.56°±10.4°, respectively, which were statistically significant compared with the preoperative results. There was no significant difference between the two groups in preoperative and final follow-up. The average bone graft fusion time of the A-P group was 9.2±4.9 months, and the average bone graft fusion time of the P group was 9.5±4.7 months. There was no statistically significant difference in the bone graft fusion time between the two groups ( t=0.547, P=0.382). Postoperative complications occurred in a total of 8 cases in the two groups, including 6 cases (21.7%) in the combined approach group and 2 cases (8.3%) in the posterior approach group. The incidence of complications in the posterior approach group was significantly lower than that in the combined approach group. Conclusion:The clinical and imaging results of the treatment of basilar depression with atlantoaxial dislocation by one-stage posterior release reduction and internal fixation are basically the same as those obtained by the anterior and posterior combined approach, but the complication rate of the posterior approach is significantly lower than that of the anterior and posterior combined approach.

Surgical treatment of post-traumatic epiphyseolisthesis at odontoid process in children / 中华骨科杂志

Objective:To evaluated the indications, methods, outcomes and prognosis of surgical treatment for post-traumatic epiphyseolisthesis at odontoid process in children.Methods:Retrospective analysis was performed on 5 cases of children with delayed epiphyseolisthesis of odontoid process in our institution from July 2009 to October 2016, including 1 male and 4 females. Initial surgery age were at1.7~5.4 years old, averaged (39.6±19.4) months and were 0.67-8 months, averaged (87.0±95.1) days. Disease duration ranged from 23 days to 8 months, with an average of 88 days. X-ray, CT and MRI examinations of the occipital-cervical area were taken to evaluate the type of the fracture and the severity of spinal cord compression. Children were treated with anterior loosening combined with posterior fixation fusion or posterior loosening reduction and internal fixation respectively.The function of spinal cord was evaluated by Frankel scale at pre- and post- operation. During the follow-up, X-ray and CT were performed to assess the fusion condition of the grafted bone.Results:The duration of operation was ranged from 75-145 months, with an average of (101.0±20.7) months; Blood loss ranged from 50-100 ml, with an average of (70.0±21.2) ml; follow-up duration ranged from 6 to 48 months, with an average of (23.5±17.6) months. Two cases preoperatively evaluated as Frankel C and D recovered to postoperative Frankel E. Among the five cases, two received satisfactory reduction, two cases received incomplete reduction, and one experienced failure reduction. The epiphyseolisthesis and bone grafted sites achieved solid fusion at 6-15 months after surgery, with an average of (9.5±3.4) months. The physiological curvature of cervical remained well without bone resorption, nonunion, pseudoarthrosis, as well as screw loosening or broken. Internal fixation of 2 cases were removed.Conclusion:Children with post-traumatic epiphyseolisthesis at odontoid process are not common in clinical practice. The detailed diagnosis of medical history, physical examination and comprehensive imaging evaluation. The posterior approach technique of C1-2 was feasible and effective, which could obtain decompression, reconstruction andstability all together.

The Nomogram model in predicting prognosis of hepatocellular carcinoma patients based on four inflammatory markers / 中华肝胆外科杂志

Objective:To construct a Nomogram model in predicting recurrence-free survival (RFS) and overall survival (OS) at six months, one year and two years after hepatocellular carcinoma (HCC) resection by using inflammatory markers combined with other routine clinical indicators.Methods:The data of 314 patients with HCC who underwent first time hepatectomy at Beijing Chaoyang Emergency Rescue Center and Air Force Characteristic Medical Center from January 2013 to January 2018 were analyzed. HCC patients who underwent hepatectomy at the First Medical Center of PLA General Hospital from January 2011 to January 2016 ( n=106) were used as the external validation group. Univariate and multivariate Cox proportional risk model was used to analyze independent risk factors of recurrence and death in HCC patients. A Nomogram model was constructed based on independent risk factors. Validation of the efficacy of the Nomogram model was done based on external data. Results:In the experimental group, 174 patients relapsed. The median RFS was 26 months. The 6 months, 1 year and 2 years RFS were 26.8%, 43.9%, and 68.8%, respectively. A total of 142 patients had died. The median survival time was 30 months. The 6 months, 1 year and 2 years OS were 5.9%, 23.6% and 63.1%, respectively. In the external validation group, 63 patients had developed recurrence, with a median RFS time of 28 months. The 6 months, 1 year and 2 years RFS were 26.4%, 45.3%, 54.7%, respectively. The median survival time was 31 months. The 6 months, 1 year and 2 years OS were 7.5%, 25.5%, 46.6%, respectively. Tumor size (>6.0 cm, HR: 1.447), vascular invasion ( HR: 1.408), TBil (>0.94 mg/dl, HR: 1.949), NLR (>2.54, HR: 2.843), AGR (≤0.88, HR: 2.447) were independent risk factors of HCC recurrence ( P<0.05). Tumor size (>6.0 cm, HR: 2.207), vascular invasion ( HR: 1.529), and NLR (>2.54, HR: 2.708) were independent risk factors of death for HCC patients ( P<0.05). The C-indexes of half-year, one-year and two-year RFS were 0.764 (95% CI: 0.677-0.854), 0.710 (95% CI: 0.615-0.824) and 0.673 (95% CI: 0.601-0.786), respectively. The C-indexes of half-year OS, one-year OS and two-year OS were 0.729 (95% CI: 0.648-0.841), 0.708 (95% CI: 0.608-0.813) and 0.664 (95% CI: 0.618-0.771), respectively. Conclusion:In this study, the construction of a Nomogram model in predicting prognosis of HCC patients was helpful to guide clinicians in improving preoperative treatment plans and in providing ideas for individualized treatment of patients.