Microstructural Changes in the Cerebral White Matter After 12 Months of CPAP Treatment for Moderate to Severe Obstructive Sleep Apnoea: A TBSS Study.

Introduction: Continuous positive airway pressure (CPAP) therapy improves clinical symptoms in patients with obstructive sleep apnea (OSA); however, the mechanism of this clinical improvement and how it may be associated with the restoration of white matter (WM) structures in the brain is unclear. Therefore, this study investigated the relationship between the structural recovery of brain WM and improvements in cognitive function and emotion after long-term (12 months) CPAP treatment in patients with OSA. Methods: We collected data from 17 patients with OSA before and 12 months after CPAP treatment, including sleep monitoring, clinical assessment, and diffusion tensor imaging (DTI) magnetic resonance imaging. Results: We observed a partial reversible recovery of brain WM (mean and radial diffusion coefficients) after treatment. This recovery involved the commissural fibers (cingulum, body of corpus callosum), projection fibers (retrolenticular part of the internal capsule, posterior thalamic radiation, posterior limb of the internal capsule, superior corona radiata, posterior corona radiata), association fibers (external capsule, superior longitudinal fasciculus, inferior longitudinal fasciculus), and other regions. In addition, the improvements in WM fibers in one part of the brain significantly were correlated with the Hamilton Anxiety Scale and Hamilton Depression Scale scores. Discussion: Our results suggest that reversible recovery of reduced brain WM integrity due to OSA may require longer CPAP treatment. Moreover, changes in the integrity of the commissural fibers were associated with emotion regulation. These restored WM areas may explain the cognitive and mood improvements observed after OSA treatment.

Identification of a natural PLA2 inhibitor from the marine fungus Aspergillus sp. c1 for MAFLD treatment that suppressed lipotoxicity by inhibiting the IRE-1α/XBP-1s axis and JNK signaling

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

CCL21-DC in situ vaccination in murine NSCLC overcomes resistance to immunotherapy and generates systemic tumor-specific immunity.

BACKGROUND: Despite recent advances in immunotherapy, many patients with non-small cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICI). Resistance to ICI may be driven by suboptimal priming of antitumor T lymphocytes due to poor antigen presentation as well as their exclusion and impairment by the immunosuppressive tumor microenvironment (TME). In a recent phase I trial in patients with NSCLC, in situ vaccination (ISV) with dendritic cells engineered to secrete CCL21 (CCL21-DC), a chemokine that facilitates the recruitment of T cells and DC, promoted T lymphocyte tumor infiltration and PD-L1 upregulation. METHODS: Murine models of NSCLC with distinct driver mutations (KrasG12D/P53+/-/Lkb1-/- (KPL); KrasG12D/P53+/- (KP); and KrasG12D (K)) and varying tumor mutational burden were used to evaluate the efficacy of combination therapy with CCL21-DC ISV plus ICI. Comprehensive analyses of longitudinal preclinical samples by flow cytometry, single cell RNA-sequencing (scRNA-seq) and whole-exome sequencing were performed to assess mechanisms of combination therapy. RESULTS: ISV with CCL21-DC sensitized immune-resistant murine NSCLCs to ICI and led to the establishment of tumor-specific immune memory. Immunophenotyping revealed that CCL21-DC obliterated tumor-promoting neutrophils, promoted sustained infiltration of CD8 cytolytic and CD4 Th1 lymphocytes and enriched progenitor T cells in the TME. Addition of ICI to CCL21-DC further enhanced the expansion and effector function of T cells both locally and systemically. Longitudinal evaluation of tumor mutation profiles revealed that CCL21-DC plus ICI induced immunoediting of tumor subclones, consistent with the broadening of tumor-specific T cell responses. CONCLUSIONS: CCL21-DC ISV synergizes with anti-PD-1 to eradicate murine NSCLC. Our data support the clinical application of CCL21-DC ISV in combination with checkpoint inhibition for patients with NSCLC.

Status Quo and Research Progress in Diagnosis and Treatment of Patients With Diabetes Mellitus and Chronic Kidney Disease / 中国医学科学院学报

As the incidence of diabetes mellitus is rapidly increasing worldwide,that of related complications,such as diabetic kidney disease(DKD),also increases,conferring a heavy economic burden on the patients,families,society,and government.Diabetes mellitus complicated with chronic kidney disease(CKD)includes DKD and the CKD caused by other reasons.Because of the insufficient knowledge about CKD,the assessment of diabetes mellitus complicated with CKD remains to be improved.The therapies for diabetes mellitus complicated with CKD focus on reducing the risk factors.In clinical practice,DKD may not be the CKD caused by diabetes.According to clinical criteria,some non-diabetic kidney disease may be misdiagnosed as DKD and not be treated accurately.This review summarizes the status quo and research progress in the assessment,diagnosis,and treatment of diabetes mellitus complicated with CKD and predicts the directions of future research in this field.

Research progress of targeting miRNAs in prevention and treatment of ventricular remodeling after myocardial infarction / 中国药理学通报

Myocardial infarction is one of the leading causes of death worldwide, appearing at the last point of atherosclerotic plaque progression and unstable rupture. Impaired cellular signals after myocardial infarction leads to maladaptive changes, leading to ventricular remodeling and heart failure. MicroRNAs (miRNAs/miRs) are a kind of non-coding small RNAs that negatively regulate gene expression and regulate protein synthesis rate by changing the stability of targeted mRNA. This article reviews the latest research progress on the involvement of miRNAs in the progression of atherosclerotic plaques, the molecular mechanism of cardiac injury and subsequent remodeling during infarction, as well as the results of clinical studies, and puts forward the problems and limitations of targeted miRNAs in the treatment of cardiovascular diseases such as myocardial infarction and ventricular remodeling.

Baicalin modulates let-7i-3p/PI3K/Akt/NF-KB signaling axis to reduce NLRP3 inflammasome activation in fibroblast like synoviocytes of rheumatoid arthritis / 中国药理学通报

Aim To study the effect of baicalin on the activation of NLRP3 inflammasomes in human fibroblast like synoviocytes of rheumatoid arthritis ( HFLS-RA) and its mechanism. Methods To confirm that baicalin alleviated the activation of NLRP3 inflammasome in HFLS-RA, immunofluorescence was used to observe the expression of NLRP3 before and after baicalin treatment. Western blot was used to detect the protein expression of p-PI3K, p-Akt, NF-κB p65, NL-RP3, ASC and caspase-1 after baicalin treatment for 48 h, and ELISA was employed to detect the contents of IL-1 and IL-18 in the supernatents. In order to explore the mechanism of baicalin alleviating the activation of NLRP3 inflammasome, double luciferin and Westen blot analysis were applied to verify the corresponding relationship between let-7i-3p and PIK3CA. RT-qPCR was utilized to determine the expression of let-7i-3p and PI3K before and after baicalin intervention. let-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasomes. Results Baicalin (50, 100 mg · L

Effect of Linggui Zhugan Decoction on myocardial infarction induced heart failure in rats based on Nrf2/BNIP3 pathway and its mechanism / 中国药理学通报

Aim To investigate whether Linggui Zhugan Decoction ( LGZGD) can inhibit ventricular remodeling and prevent heart failure in rats after myocardial infarction by regulating Nrf2/BNIP3 pathway. Methods The model of heart failure after myocardial infarction was established by left coronary artery ligation in rats. Two weeks after modeling, all rats were randomly divided into model group, LGZGD group, and captopril group. Meanwhile sham operation group was set up. The rats were given continuous intragastric administration with drug or distilled water for 28 days, once a day. The behavioral signs of rats in each group were observed. The cardiac function of rats in each group was examined by echocardiography. Serum BNP and NT-ProBNP content were detected by enzyme -linked immunoassay; The changes of myocardial his-topathological and collagen fibers in rats were detected using sirius staining. The contents of oxidative stress index including ROS, SOD in myocardial tissue of rats in each group were observed by DCFH-DA fluorescent probe and Enzyme-linked immunoassay. The ultra-structure of mitochondria was observed by transmission electron microscopy. Expressions of apoptotic proteins ( mitochondrial CytC, cytoplasmic CytC) were detected by Western blot. Expression of proteins related to the Nrf2/BNIP3 pathway were examined by immunofluorescence and Western blot. Results LGZGD could significantly improve the cardiac function of rats, reduce the contents of BNP and NT-ProBNP, inhibit the excessive deposition of collagen in myocardial interstiti-um, reduce ROS, increase the content of SOD, improve mitochondrial structure damage, up-regulate the expression of Nrf2 and nuclear translocation, and reduce the expression of BNIP3. Conclusions LGZGD can inhibit the ventricular remodeling and prevent the occurrence of heart failure after myocardial infarction. Its pharmacological effects are mainly related to regulating the Nrf2/BNIP3 pathway, activating Nrf2, promoting its nuclear transfer, and further down-regulating BNIP3, protecting mitochondrial function, and reducing cardiomyocyte apoptosis.

Eucommia lignans alleviate the progression of diabetic nephropathy through mediating the AR/Nrf2/HO-1/AMPK axis in vivo and in vitro / 中国天然药物

Lignans derived from Eucommia ulmoides Oliver (Eucommia lignans) inhibit the progression of inflammatory diseases, while their effect on the progression of diabetic nephropathy (DN) remained unclear. This work was designed to assess the function of Eucommia lignans in DN. The major constituents of Eucommia lignans were analyzed by UPLC-Q-TOF-MS/MS. The binding between Eucommia lignans and aldose reductase (AR) was predicted by molecular docking. Eucommia lignans (200, 100, and 50 mg·kg-1) were used in model animals to evaluate their renal function changes. Rat glomerular mesangial cells (HBZY-1) were transfected with sh-AR, sh-AMPK, and oe-AR in the presence of high glucose (HG) or HG combined with Eucommia lignans to evaluate whether Eucommia lignans affected HG-induced cell injury and mitochondrial dysfunction through the AR/Nrf2/HO-1/AMPK axis. Eucommia lignans significantly attenuated the progression of DN in vivo. Eucommia lignans notably reversed HG-induced upregulation of inflammatory cytokines and mitochondrial injury, while downregulating the levels of Cyto c, caspase 9, AR, and NOX4 in HBZY-1 cells. In contrast, HG-induced downregulation of Nrf2, HO-1 and p-AMPKα levels were abolished by Eucommia lignans. Meanwhile, knockdown of AR exerted similar therapeutic effect of Eucommia lignans on DN progression, and AR overexpression reversed the effect of Eucommia lignans. Eucommia lignans alleviated renal injury through the AR/Nrf2/HO-1/AMPK axis. Thus, these findings might provide evidence for the use of Eucommia lignans in treating DN.

Mining and analysis of risperidone adverse event signals based on FAERS database / 中国药房

OBJECTIVE To provide reference for safe use of risperidone in clinic. METHODS Data mining and analysis of risperidone-related adverse drug event （ADE） reports from the first quarter of 2017 to the third quarter of 2021 in the United States FAERS database were carried out using reported odds ratio and composite criteria methods from Medicines and Healthcare Products Regulatory Agency. RESULTS There were 101 181 ADE reports with risperidone as the primary suspect drug，involving a total of 33 179 patients. Among those reports，the male-to-female ratio was about 6.21 to 1； most of them were ＜18 years old （15.01%）； ADE was mainly reported by consumers （69.74%） and mainly reported by the United States （79.72%）； oral dosage form was the most used，accounting for 83.71%. A total of 409 ADE signals were obtained，including male breast development， pseudogynecomastia，abnormal increase in body mass，hyperprolactinemia and Wellens syndrome，etc. Twenty-six systems and organs were involved，mainly including reproductive system and breast diseases，various injuries，poisoning and operational complications， mental diseases，metabolic and nutritional diseases，and various nervous system diseases，etc. CONCLUSIONS The common ADE signals of risperidone and the system involved are consistent with the instructions，but we should also be alert to the ADE not recorded in the instruction，such as Wellens syndrome，fibroproliferative endocarditis，cavernous degeneration of portal vein，rabbit syndrome，etc.

Effect of group mindfulness-based stress reduction therapy in managing comorbid depression in patients with stable chronic obstructive pulmonary disease / 四川精神卫生

BackgroundChronic obstructive pulmonary disease （COPD） is a common chronic respiratory disease， and patients with COPD often experience substantially emotional difficulties， such as anxiety and depression， all of which may cause serious detriment to the prognosis of patients. As a non-pharmacological intervention in clinical practice， group mindfulness-based stress reduction therapy （MBSR） is beginning to emerge， while has rarely been studied in COPD patients with concurrent emotional difficulties. ObjectiveTo evaluate the effects of group MBSR on depression， state of mindfulness and pulmonary function in stable COPD patients， so as to provide references for the application of group MBSR in patients with COPD. MethodsA total of 97 patients with stable COPD who were followed up in the Department of Respiratory and Critical Care Medicine of Mianyang Third People's Hospital from January to October 2019 were selected as the study objects， and they were assigned into study group （n=50） and control group （n=47） by random number table method. All individuals received routine medication therapy and an 8-week health education， based on this， participants in study group partook an 8-week intervention comprising group MBSR. At the baseline， 4 weeks and 8 weeks of intervention， participants were assessed with Self-rating Depression Scale （SDS）， Five Facet Mindfulness Questionnaire （FFMQ） and COPD Assessment Test （CAT）， as well as the pulmonary function testing. ResultsThere were 41 patients in study group and 42 cases in control group completed the study. The group * time interaction was interpreted as significant between two groups for SDS， FFMQ and CAT scores （F=54.858， 86.161， 69.862， P<0.01）. Baseline SDS， FFMQ and CAT scores of the two groups yielded no statistical difference between two groups （F=0.240， 0.052， 0.019， P>0.05）， while study group scored lower on SDS and CAT （F=12.900， 38.511， 7.797， 28.824， P<0.01） and higher on FFMQ （F=27.324， 82.412， P<0.01） than those of the control group after 4 and 8 weeks of intervention. With the prolongation of intervention time in study group， participants demonstrated an overall reduction in SDS and CAT scores （F=109.753， 124.144， P<0.01）， and an increase in FFMQ scores （F=228.194， P<0.01）. There were no between-group differences in forced expiratory volume in one second as percentage of predicted volume （FEV1%pred） after 4 and 8 weeks of intervention （F=0.104， P=0.748） ， and the within-group changes in FEV1%pred value over the intervention period in study group was not statistical （F=0.561， P=0.458）. ConclusionGroup MBSR may help relieve depressive symptoms， enhance mindfulness level， and alleviate clinical symptoms in stable COPD patients， but has no effect on pulmonary function. ［Funded by Mianyang Health and Health Commission Scientific Research Project （number， 201916）］

Recognition models of cigarette smoking behavior by real-time indoor PM2.5 concentrations in public places / 环境与职业医学

Background Public places are frequently polluted by cigarette smoking, and there is a lack of accurate, real-time, and intelligent monitoring technology to identify smoking behavior. It is necessary to develop a tool to identify cigarette smoking behavior in public places for more efficient control of cigarette smoking and better indoor air quality. Objective To construct a model for recognizing cigarette smoking behavior based on real-time indoor concentrations of PM2.5 in public places. Methods Real-time indoor PM2.5 concentrations were measured for at least 7 continuous days in 10 arbitrarily selected places (6 public service providers and and 4 office or other places) from Oct. to Nov. 2022 in Pudong New Area, Shanghai. Indoor nicotine concentrations were monitored with passive samplers simultaneously. Outdoor PM2.5 concentration data were obtained from three municipal environmental monitoring stations which were nearest to each monitoring point during the same period. Mann-Whitney U test was used to compare indoor and outdoor means of PM2.5 concentrations, and Spearman rank correlation was used to analyze indoor PM2.5 and nicotine concentrations. An interactive plot and a random forest model was applied to examine the association between video observation validated indoor smoking behavior and real-time indoor PM2.5 concentrations in an Internet cafe. Results The average indoor PM2.5 concentration in the places providing public services [(97.5±149.3) µg·m−3] was significantly higher than that in office and other places [(19.8±12.2) µg·m−3] (P=0.011). The indoor/outdoor ratio (I/O ratio) of PM2.5 concentration in the public service providers ranged from 1.1 to 19.0. Furthermore, the indoor PM2.5 concentrations in the 10 public places were significantly correlated with the nicotine concentrations (rs=0.969, P<0.001). Among them, the top 3 highly polluted places were Internet cafes, chess and card rooms, and KTV. The results of random forest modeling showed that, for synchronous real-time PM2.5 concentration, the area under the curve (AUC) was 0.66, while for PM2.5 concentration at a lag of 4 min after the incidence of smoking behavior, the AUC increased to 0.72. Conclusion The indoor PM2.5 concentrations in public places are highly correlated with smoking behavior. Based on real-time indoor PM2.5 monitoring, a preliminary recognition model for smoking behavior is constructed with acceptable accuracy, indicating its potential values applied in smoking control and management in public places.

Combining extracorporeal shock wave treatment with proprioceptive neuromuscular facilitation can improve the lower limb motor function of stroke survivors with foot drop / 中华物理医学与康复杂志

Objective:To observe any effect of combining extracorporeal shock wave stimulation with proprioceptive neuromuscular facilitation (PNF) on the lower limb motor function of stroke survivors with foot drop.Methods:Thirty-six stroke survivors with foot drop were randomly divided into an extracorporeal shock wave group, a PNF group and a combination group, each of 12. The extracorporeal shock wave group and PNF group were given those therapies alone, while the combination group was provided with both. The extracorporeal shock wave therapy protocol was 2000 times on each muscle at an intensity of 2.5 bar and a frequency of 10Hz, twice a week for 4 weeks, while the PNF was provided at least 3 times per week for 4 weeks. Before and after the intervention, all of the participants were evaluated using the modified Ashworth scale (MAS), the 10-metre walk test (10 MWT) and the Fugl-Meyer lower limb motor function scale (FMA). Active range of the ankle joint and toe out angle were also observed.Results:After the intervention the lower limb muscle tone had decreased significantly in 8 of the PNF group members and in 9 of those in the extracorporeal shock wave group, but it has decreased significantly in all 12 members of the combination group. And the average magnitude of the improvement was also significantly greater in the combination group than in the other two groups. Moreover, significant differences were observed in the active range of the ankle joint after the treatment in the combination group, but not in the other two groups. After the intervention the average 10 MWT times and FMA scores of the PNF and combination groups had improved significantly, but not those of the extracorporeal shock wave group, but significant improvement in toe out angles was observed in all three groups, though the average improvement in the combination group was significantly greater than in the other 2 groups.Conclusion:Combining extracorporeal shock waves with PNF can effectively improve the lower limb motor function of stroke survivors with foot drop.

The influence of embodied emotion priming on the attentional bias of individuals with depression tendency / 中华行为医学与脑科学杂志

Objective:To explore the effects of embodied emotion priming on attentional bias of individuals with depression tendency.Methods:From June to December 2018, a total of 91 college students with depression tendency were recruited to participate in the experiment.A 3(embodied emotion priming: positive priming, negative priming and no priming) × 2 (emotional face: happy and sad) mixed design was adopted to measure the attentional bias of individuals with depression tendency using the dot probe paradigm. SPSS 22.0 statistical software was used for repeated measurement analysis of variance.Results:In terms of attentional bias, the interaction effect between embodied emotion priming types and emotional faces was significant ( F(2, 88)=5.97, P=0.004, ηp2=0.119). Further simple effect analysis showed that, under the happy-face condition, participants' attentional bias reaction time(△RT) was significantly higher when primed with embodied positive emotion than those primed with embodied negative emotion((14.30±18.23)ms, (-6.53±38.17)ms, P<0.05). The participants' attentional bias △RT was significantly lower when primed with embodied negative emotion than participants with no priming ((-6.53±38.17)ms, (9.16±30.62)ms, P<0.05). Under the sad-face condition, the participants' attentional bias △RT was significantly higher when primed with embodied negative emotion((28.22±35.33)ms) than participants primed with embodied positive emotion((11.71±29.24)ms, P<0.05) and no priming ((7.63±30.60)ms, P<0.05). Conclusion:Embodied emotion priming can affect the attentional bias of individuals with depression tendency.

Staging study of single-channel sleep EEG signals based on data augmentation.

Introduction: Accurate sleep staging is an essential basis for sleep quality assessment and plays an important role in sleep quality research. However, the occupancy of different sleep stages is unbalanced throughout the sleep process, which makes the EEG datasets of different sleep stages have a class imbalance, which will eventually affect the automatic assessment of sleep stages. Method: In this paper, we propose a Residual Dense Block and Deep Convolutional Generative Adversarial Network (RDB-DCGAN) data augmentation model based on the DCGAN and RDB, which takes two-dimensional continuous wavelet time-frequency maps as input, expands the minority class of sleep EEG data and later performs sleep staging by Convolutional Neural Network (CNN). Results and discussion: The results of the CNN classification comparison test with the publicly available dataset Sleep-EDF show that the overall sleep staging accuracy of each stage after data augmentation is improved by 6%, especially the N1 stage, which has low classification accuracy due to less original data, also has a significant improvement of 19%. It is fully verified that data augmentation by improving the DCGAN model can effectively improve the classification problem of the class imbalance sleep dataset.

Effect of foliage applied chitosan-based silicon nanoparticles on arsenic uptake and translocation in rice (Oryza sativa L.).

In this study, chitosan-based silicon nanoparticles (Chsi-NPs) are prepared that primarily consists of C (57.9%), O (31.3%), N (5.6%), and Si (3.5%) and are 10-180 nm in size. We then explore the effect on the foliage applied on rice planted on soil contaminated with 104 mg·kg-1 arsenic (As); low (3 mg·L-1)and high (15 mg·L-1) doses of the foliar Chsi-NPs are administered during the rice grain filling stage. The results showed that the higher dose foliar Chsi-NPs treatment reduced the As concentration in the grain by 61.2% but increased As concentration in the leaves by 47.1% compared to the control treatment. The foliar spraying of the Chsi-NPs inhibited As transport to the grain by facilitating the attachment of As to the cell wall, with higher doses of the foliar Chsi-NPs treatment increased by 8.7%. The foliar spraying of Chsi-NPs increased the malondialdehyde levels by 18.4%, the catalase activity by 49.0%, and the glutathione activity by 99.0%. These results indicated that the foliar Chsi-NPs application was effective for alleviating As toxicity and accumulation in rice. This study provides a novel method for effectively alleviating As accumulation in rice.

Functional outcomes of 100 patients with adenocarcinoma of the esophagogastric junction undergoing Cheng's GIRAFFE(®) reconstruction after proximal gastrectomy / 中华胃肠外科杂志

Objective: To investigate the functional outcomes and postoperative complications of Cheng's GIRAFFE reconstruction after proximal gastrectomy. Methods: A descriptive case series study was conducted. Clinical data of 100 patients with adenocarcinoma of the esophagogastric junction who underwent Cheng's GIRAFFE reconstruction after proximal gastrectomy in Cancer Hospital of University of Chinese Academy of Sciences (64 cases), Zhejiang Provincial Hospital of Chinese Medicine (24 cases), Lishui Central Hospital (10 cases), Huzhou Central Hospital (1 case) and Ningbo Lihuili Hospital (1 case) from September 2017 to June 2021 were retrospectively analyzed. Of 100 patients, 64 were males and 36 were females; the mean age was (61.3 ± 11.1) years and the BMI was (22.7±11.1) kg/m(2). For TNM stage, 68 patients were stage IA, 24 were stage IIA and 8 were stage IIB. Postoperative functional results and postoperative complications of radical gastrectomy with Giraffe reconstruction were analyzed and summarized. Gastroesophageal reflux disease questionnaire (RDQ) score and postoperative endoscopy were used to evaluate the occurrence of reflux esophagitis and its grade (grade N, grade A, grade B, grade C, and grade D from mild to severe reflux). The continuous data conforming to normal distribution were expressed as (mean ± standard deviation), and those with skewed distribution were presented as median (Q1, Q3). Results: All the 100 patients successfully completed R0 resection, including 77 patients undergoing laparoscopic surgery and 23 patients undergoing laparotomy. The Giraffe anastomosis time was (38.6±14.0) min; the blood loss was (73.0±18.4) ml; the postoperative hospital stay was 9.5 (8.2, 13.0) d; the hospitalization cost was (6.0±0.3) ten thousand yuan. Fourteen cases developed perioperative complications (14.0%), including 7 cases of pleural effusion or pneumonia, 3 cases of anastomotic leakage, 2 cases of gastric emptying disorder, 1 case of gastrointestinal hemorrhage and 1 case of anastomotic stenosis, who were all improved and discharged after symptomatic management. Patients were followed up for (33.3±1.6) months. Eight patients were found to have reflux symptoms by RDQ scale six months after surgery, and 11 patients (11/100,11.0%) were found to have reflux esophagitis by gastroscopy, including 6 in grade A, 3 in grade B, and 2 in grade C. All the patients could control their reflux symptoms with behavioral guidance or oral PPIs. Conclusion: Cheng's GIRAFFE reconstruction has good anti-reflux efficacy and gastric emptying function; it can be one of the choices of reconstruction methods after proximal gastrectomy.

Experience and thoughts on digestive tract reconstruction after radical resection of adenocarcinoma of the esophagogastric junction / 中华胃肠外科杂志

In the surgical treatment of adenocarcinoma of the esophagogastric junction (AEG), the scope of lymph node dissection, surgical approach selection, extent of tumor resection and digestive tract reconstruction have always been controversial, with the digestive tract reconstruction in AEG facing many challenges especially. The digestive tract reconstruction is related to the extent of resection. At present, the digestive tract reconstruction after total gastrectomy includes Roux-en-Y anastomosis, jejunum interposition and its derivatives. According to different reconstruction methods, they can be divided into tube anastomosis, linear anastomosis and manual anastomosis. Anti-reflux digestive tract reconstruction after proximal gastrectomy mainly includes esophagogastric anastomosis, interposition jejunum and double channel anastomosis. At present, double channel anastomosis is the most common reconstruction method in China. Based on the concept of interposition tubular stomach and reconstruction of gastric angle for anti-reflux, we propose "Giraffe" anastomosis, which moves artificial fundus and His angle downward to retain more residual stomach, showing good gastric emptying and anti-reflux effect. In this paper, combined with our clinical experience and understanding, we discuss the selection and technical key points of digestive tract reconstruction methods in AEG, and suggest that composite anti-reflux mechanism design may be the development trend of anti-reflux reconstruction in the future. The composite mechanism includes the retention of gastric electrical pacemaker in greater curvature of the middle part of gastric body to increase the emptying capacity of residual stomach, the reconstruction of gastric fundus and His angle anti-reflux barrier, and the establishment of an interposition tubular stomach acting as a buffer zone in Giraffe construction, and so on.

Xiao Xianxiongtang Regulates Ca2+ Load and Inhibits Epithelial-mesenchymal Transition， Invasion， and Migration of MGC-803 Cells： Based on Wnt5a/ Ca2+/NFAT Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect of Xiao Xianxiongtang （XXXT） on the transforming growth factor （TGF）-β1-induced invasion， metastasis， and epithelial-mesenchymal transition （EMT） of gastric cancer MGC-803 cells and the underlying mechanism. MethodThe molecular docking between XXXT and nuclear factor of activated T cells （NFAT） was performed by CB-DOCK （http：//clab.labshare.cn/cb-dock/）. The invasion and metastasis model of MGC-803 cells was established with 10 μg·L-1 TGF-β1. MGC-803 cells were classified into blank group， model group， 0.1 g·L-1 XXXT group， 0.2 g·L-1 XXXT group， and 0.4 g·L-1 XXXT group. For further clarifying the key role of Wnt5a/Ca2+/NFAT signaling pathway in the inhibition of XXXT on gastric cancer， MGC-803 cells were transfected with Wnt5a overexpression plasmid， and then the cells were classified into blank plasmid group， Wnt5a-OE group， blank plasmid + XXXT （0.4 g·L-1） group， and Wnt5a-OE + XXXT （0.4 g·L-1） group. Cell viability was determined by cell counting kit-8 （CCK-8） assay， cell invasion and migration ability by Transwell invasion assay and wound healing assay， expression of EMT-related proteins （E-cadherin， N-cadherin， Vimentin， Snail） and Wnt5a/Ca2+/NFAT signaling pathway-related key proteins ［Wnt5a， calcineurin （CaN）， NFAT1， and p-NFAT1］ by Western blot， and changes in intracellular Ca2+ concentration by immunofluorescence assay. ResultMolecular docking suggested that XXXT acted on Wnt5a/Ca2+/NFAT signaling pathway. XXXT （0.1， 0.2， 0.4 g·L-1） significantly promoted the loss of MGC-803 cell viability （P<0.05，P<0.01）. It inhibited cells from invading the transwell lower chamber and slowed down the healing of cell wounds in a dose-dependent manner （P<0.05， P<0.01）. Moreover， it promoted the expression of E-cadherin while suppressed the expression of N-cadherin， Vimentin， and Snail （P<0.05， P<0.01）. Further experiments showed that XXXT could inhibit the expression of Wnt5a， CaN， NFAT1， and p-NFAT1， and reduce the nuclear expression of NFAT1 and the transcription activity mediated by NFAT1， so as to reduce the cellular Ca2+ concentration （P<0.05， P<0.01）. XXXT can reverse the effect of Wnt5a （P<0.05， P<0.01）. ConclusionXXXT can attenuate the invasion， metastasis， and EMT of MGC-803 cells via the Wnt5a/Ca2+/NFAT pathway， thereby weakening the tumor-promoting effect of TGF-β1. In summary， XXXT may exert therapeutic effect on gastric cancer by regulating the invasion， metastasis， and EMT of gastric cancer cells.

Modified Xiao Xianxiongtang Inhibits Epithelial-Mesenchymal Transition of Human Gastric Cancer MGC803 Cells via Wnt/β-catenin Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the inhibitory effect of modified Xiao Xianxiongtang on epithelial-mesenchymal transition （EMT） of human gastric cancer MGC803 cells and its relationship with secretory glycoprotein Wnt/β-catenin pathway. MethodThe BALB/c nude mice were implanted with human gastric cancer MGC803 cell suspension in the heterotopic subcutaneous position for inducing tumor. After successful modeling， they were randomly divided into the model group， low-， medium-， and high-dose （16.0，32.0，and 64.0 g·kg-1） groups of modified Xiao Xianxiongtang， and capecitabine （400 mg·kg-1） group， with eight mice in each group， and gavaged with the corresponding drugs， once per day， for 28 consecutive days. Those in the capecitabine group received one-week discontinuation after every two weeks of treatment. The general state and body weight of the nude mice were observed， and the transplanted tumor volume was measured. After being killed， they were weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was carried out for observing the pathological changes in transplanted tumor tissues. The gene and protein expression levels of Wnt1 and β-catenin were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， followed by the determination of matrix metalloproteinase-9 （MMP-9）， vascular endothelial growth factor （VEGF）， N-cadherin， E-cadherin， Vimentin， and Snail protein expression by Western blot. The expression levels of cyclooxygenase 2 （COX2） and prostaglandin E2 （PGE2） were detected by enzyme-linked immunosorbent assay （ELISA）. ResultIt was found that the transplanted tumor in each group showed different growth trends with time， with the most obvious growth observed in the model group. Compared with the model group， the low-， medium-， and high-dose modified Xiao Xianxiongtang groups exhibited reduced tumor volume and slowed growth to varying degrees over time. After medication for days 7，14，21，and 28， the tumor volumes in the low- and high-dose modified Xiao Xianxiongtang groups and capecitabine group declined （P<0.05， P<0.01）， and that in the medium-dose Xiao Xianxiongtang group was also remarkably reduced after medication for days 14，21，and 28 （P<0.01）. Compared with the model group， the high-dose modified Xiao Xianxiongtang group and capecitabine group showed a significant reduction in the relative tumor volume after treatment for days 7，14，21，28 （P<0.01）， and the low- and medium-dose modified Xiao Xianxiongtang groups also presented with decreased relative tumor volume after treatment for days 14，21，28 （P<0.05， P<0.01）. Compared with the model group， the modified Xiao Xianxiongtang at low， medium， and high doses and capecitabine all increased the tumor inhibition rate to varying degrees （P<0.01）， down-regulated the mRNA and protein expression levels of Wnt1 and β-catenin in tumor tissue （P<0.05， P<0.01） and protein expression levels of MMP-9， VEGF， N-cadherin， Vimentin， and Snail （P<0.05， P<0.01）， up-regulated E-cadherin protein expression （P<0.05， P<0.01）， and reduced COX2 and PGE2 contents （P<0.05， P<0.01）. ConclusionModified Xiao Xianxiongtang inhibits the EMT of human gastric cancer MGC803 cell-transplanted tumor， which may be related to Wnt/β-catenin pathway.

Ginsenoside Rg_1 protects PC12 cells against Aβ-induced injury through promotion of mitophagy by PINK1/parkin activation / 中国中药杂志

Amyloid β-protein(Aβ) deposition in the brain is directly responsible for neuronal mitochondrial damage of Alzheimer's disease(AD) patients. Mitophagy, which removes damaged mitochondria, is a vital mode of neuron protection. Ginsenoside Rg_1(Rg_1), with neuroprotective effect, has displayed promising potential for AD treatment. However, the mechanism underlying the neuroprotective effect of Rg_1 has not been fully elucidated. The present study investigated the effects of ginsenoside Rg_(1 )on the autophagy of PC12 cells injured by Aβ_(25-35) to gain insight into the neuroprotective mechanism of Rg_1. The autophagy inducer rapamycin and the autophagy inhi-bitor chloroquine were used to verify the correlation between the neuroprotective effect of Rg_1 and autophagy. The results showed that Rg_1 enhanced the viability and increased the mitochondrial membrane potential of Aβ-injured PC12 cells, while these changes were blocked by chloroquine. Furthermore, Rg_(1 )treatment increased the LC3Ⅱ/Ⅰ protein ratio, promoted the depletion of p62 protein, up-regulated the protein levels of PINK1 and parkin, and reduced the amount of autophagy adaptor OPTN, which indicated the enhancement of autophagy. After the silencing of PINK1, a key regulatory site of mitophagy, Rg_1 could not increase the expression of PINK1 and parkin or the amount of NDP52, whereas it can still increase the LC3Ⅱ/Ⅰ protein ratio and promote the depletion of OPTN protein which indicated the enhancement of autophagy. Collectively, the results of this study imply that Rg_1 can promote autophagy of PC12 cells injured by Aβ, and may reduce Aβ-induced mitochondrial damage by promoting PINK1-dependent mitophagy, which may be one of the key mechanisms of its neuroprotective effect.