Twelve-week treadmill endurance training in mice is associated with upregulation of interleukin-15 and natural killer cell activation and increases apoptosis rate in Hepa1-6 cell-derived mouse hepatomas

Regular exercise reduces the risk of malignancy and decreases the recurrence of cancer. However, the mechanisms behind this protection remain to be elucidated. Natural killer (NK) cells are lymphocytes of the innate immune system, which play essential roles in immune defense and effectively prevent cancer metastasis. Physical exercise can increase the activity of NK cells. Interleukin-15 (IL-15) is the best-studied cytokine activator of NK cells, and it was shown to have many positive functional effects on NK cells to improve antitumor responses. The aim of this study was to clarify the possible important mechanisms behind endurance exercise-induced changes in NK cell function, which may be highly correlated with IL-15. An animal model was used to study IL-15 expression level, tumor volume, cancer cell apoptosis, and NK cell infiltration after treadmill exercise. Although IL-15 was highly expressed in skeletal muscle, treadmill exercise further elevated IL-15 levels in plasma and muscle (P<0.05). In addition, tumor weight and volume of tumor-bearing mice were decreased (P<0.05), and liver tumor cell apoptosis was increased after 12 weeks of treadmill exercise (P<0.05). NK cell infiltration was upregulated in tumors from treadmill exercise mice, and the level of interferon-gamma (IFN-γ) and IL-15 were higher than in sedentary mice (P<0.05). The study indicated that regular endurance training can reduce cancer risk, which was related to increased IL-15 expression, activation of the immune killing effect of NK cells, and promotion of tumor cell apoptosis, which can ultimately control tumor growth.

Analysis of leukocyte and neutrophil changes before and after immune-related adverse events in patients treated with anti-PD-1 antibodies / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：通过对比免疫相关不良反应（irAE）发生前后血常规中主要指标的变化，为鉴别诊断irAE及感染性炎症提供新依据。方法：回顾性分析201例2018年8月至2022年6月在河南省肿瘤医院接受抗PD-1抗体治疗后出现irAE的肿瘤患者的临床资料，包括抗PD-1抗体治疗前、发生irAE前及irAE后血常规的主要指标，采用配对t检验分析治疗前后血常规指标值的统计学差异。采用定性变量的配对c2检验分析治疗前后血常规指标值的阳性率（高于正常值的比例）的统计学差异。结果：从201例患者中观察到了258次irAE，其中27例（13.4%）患者发生了2种及以上类型的irAE，214次（82.94%）irAE未引起发热；irAE发生后与抗PD-1抗体治疗前相比，白细胞计数（t=1.087, P=0.278）、中性粒细胞计数（t=0.959, P=0.338）及中性粒细胞百分比（t=0.817，P=0.414）未见明显升高，且三指标高于正常值的病例数分别为28 vs 38（χ2=1.737，P=0.187）、32 vs 44（χ2=2.222，P=0.136）、45 vs 55（χ2=1.240，P=0.265）,差异均无统计学意义。结论：irAE发生后患者外周血白细胞计数、中性粒细胞计数及中性粒细胞百分比无明显变化，这对鉴别诊断感染性炎症可能具有参考意义。

Association between low vision and sleep duration among primary and middle school students / 预防医学

Objective @#To understand the relationship between sleep duration and low vision among primary and middle school students, so as to provide the reference for promoting eye health of primary and middle school students.@* Methods @#Using stratified cluster sampling method, the students were selected from four primary schools, four junior high schools and three senior high schools in Dinghai, Putuo, Daishan and Shengsi of Zhoushan. The questionnaire for the influencing factors of myopia in the national monitoring and intervention project of common diseases and influencing factors among students in 2019 was used to collect their demography, video display terminal use, outdoor activity, parents'myopia and sleep duration. The multivariate logistic regression model was established to analyze the relationship between sleep duration and low vision among the students. @*Results @#A total of 3 016 questionnaires were sent out, and 2 932 valid ones were returned. The effective rate was 97.21%. There were 1 537 ( 52.42% ) males and 1 395 females ( 47.58% ); 947 ( 32.30% ) primary school students and 1 985 ( 67.70% ) middle school students; 2 328 ( 79.40% ) students with low vision. There were 1 022 ( 34.85% ), 903 (30.80%), 697 ( 23.77% ) and 310 ( 10.57% ) students with the daily sleep duration of <8 hours, 8-<9 hours, 9-<10 hours and ≥10 hours, respectively. The multivariate logistic regression analysis showed that the risk of low vision was lower when the daily sleep duration of students was 8-<9 hours ( OR=0.735, 95%CI: 0.561-0.963 ) and 9-<10 hours ( OR=0.605, 95%CI: 0.446-0.825 ). @*Conclusion @#Adequate sleep duration is conducive to reduce the risk of low vision among primary and middle school students.

Mortality trend of bladder cancer in Qidong from 1972 to 2016 / 预防医学

Objective@#To analyze the mortality trend of bladder cancer among residents in Qidong, Jiangsu Province from 1972 to 2016, so as to provide the basis for the prevention and treatment strategy of bladder cancer in Qidong.@*Methods@#The data of bladder cancer was collected from Qidong Cancer Registry.The crude mortality rate ( CR ), age-standardized rate by Chinese population in 2000 (CASR) and world population in 1960 ( WASR ), truncated rate (35-64 years) and cumulative rate ( 0-74 years ) were calculated. The annual percent change ( APC ) was used to analyze the trend of mortality in bladder cancer.@*Results@#During from 1972 to 2016, There were 1 497 deaths due to bladder cancer in Qidong from 1972 to 2016. The CR, CASR and WASR were 2.96/105, 1.83/105 and 1.80/105, respectively. The APCs in CR, CASR, WASR of bladder cancer were 5.29%, 1.86% and 1.81%, respectively ( P<0.05 ), showing upward trends. The truncated rate, cumulative rate and cumulative risk were 1.47/105, 0.17% and 0.17%, respectively. The CR, CASR and WASR in males were 4.71/105, 2.97/105 and 3.31/105, respectively, which was higher than that of 1.26/105, 0.75/105, and 0.66/105 in females ( P<0.05 ). The APC of CR, CASR and WASR in males were 5.71%, 1.96% and 2.17%, respectively ( P<0.05 ), all showed upward trends. For females, the APC of CR was 4.47% ( P<0.05 ), showing an upward trend, but there was no significant change in CASR and WASR ( P>0.05 ). The CR of bladder cancer was high among people aged more than 55 years. The CR in 55-64-year-old group, 65-74-year-old group and more than 75-year-old group showed upward trends, with APC of 4.50%, 2.22% and 4.51%, respectively ( P<0.05 ). @*Conclusions@#From 1972 to 2016, the mortality of bladder cancer in Qidong showed an upward trend, which was relatively high in men and people aged over 55 years.

Effects of ergosteroside combined risedronate on fracture healing and BMP-2, BMP-7 and VEGF expression in rats

Purpose To evaluate the effect of ergosterol combined with risedronate on fracture healing. Methods Sixty male Sprague Dawley fracture model rats were assigned into group A (n=20), group B (n=20), and group C (n=20) at random. All rats were fed by gavage until their sacrifice as it follows: group A with ergosteroside and risedronate, group B with risedronate, and group C with saline solution. At weeks 2 and 4, 10 rats of each group were sacrificed. Healing effect and bone tissue changes in the fractures site were assessed by using hematoxylin and eosin stain histology. Enzyme-linked immunosorbent assay was used to detect the expression of serum bone morphogenetic protein-2 (BMP-2), bone morphogenetic protein-7 (BMP-7), and vascular endothelial growth factor (VEGF). Reverse transcriptase polymerase chain reaction was applied to detect the expression of osteoprotegerin (OPG) mRNA, osteocalcin (OCN) mRNA and core-binding factor subunit-?1 (CBF-?1) mRNA. Results In terms of serum BMP-2, BMP-7, and VEGF expression at weeks 2 and 4 after gavage, group A < group B < group C (P<0.05). At week 4 after gavage, serum VEGF expression in the three groups harbored positive relationship with serum BMP-2 and BMP-7 expression (P<0.05). Regarding serum OPG, OCN and CBF-?1 mRNA expression at weeks 2 and 4 after gavage, group A

Clinical analysis for the short-term outcome of Da Vinci robotic-assisted left upper lobectomy for lung cancer / 中国胸心血管外科临床杂志

@#Objective    To summarize the clinical experience of Da Vinci robotic-assisted left upper lobectomy for treating lung cancer. Methods    We retrospectively analyzed the perioperative data of 33 patients with primary lung cancer who underwent Da Vinci robotic-assisted left upper lobectomy between December 2016 and December 2018 in our hospital. Meanwhile, the perioperative data of 41 patients with lung cancer who underwent video-assisted thoracoscopic left upper lobectomy during the same period by the same surgeon were studied as a control group. The resection was followed by the principle of "from back down to front up" way. Systemic lymph node dissection including No.4-9 was performed for all patients. Results    All patients received successful surgery with no case of conversion to thoracotomy and perioperative death. Comparing to video-assisted thoracoscopic surgery, the Da Vinci robotic-assisted left upper lobectomy had longer operating time (191.21±61.77 min vs. 154.51±38.81 min, P=0.003), more cost (82 307.75±11 859.03 yuan vs. 58 966.57±5 640.07 yuan, P=0.000), shorter chest tube duration (4.58±1.77 d vs. 5.41±1.52 d, P=0.031) and postoperative hospital stay (6.48±1.82 d vs. 7.66±2.12 d, P=0.014). However, there was no significant difference between the two groups regarding to blood loss, lymph node dissection, postoperative pain score, total chest drainage volume, chest drainage volume per day and the rate of pulmonary complications. Conclusion    The Da Vinci robotic-assisted left upper lobectomy for treating lung cancer is safe and more minimally invasive, but more expensive.

Application of magnetic surgery technique in thoracic surgery / 中国胸心血管外科临床杂志

@#The earliest research of magnetic surgery was the application of magnetic anastomotic device to anastomose the blood vessels. Now, it has been widely used for anastomosis of blood vessels, gastrointestinal tract and biliary tract. The concept of "magnetic surgery" was named firstly by LU Yi in 2010 and magnetic surgery was classified into magnetic anchoring technique, magnetic navigation technique, magnetic compression technique, magnetic tracing technique, and magnetic suspension technique. The applications of magnetic surgery in the field of thoracic surgery mainly include magnetic compression technique, magnetic anchoring technique and magnetic navigation technique. This paper summarizes the application of magnetic surgery in thoracic surgery and prospects its future development in the field of thoracic surgery.

Short-term efficacy analysis of different surgical methods for Siewert type Ⅰ and Ⅱ esophagogastric junction carcinoma / 中国胸心血管外科临床杂志

@#Objective    To compare and analyze the short-term efficacy of different surgical methods for Siewert type Ⅰ and type Ⅱ esophagogastric junction carcinoma. Methods    We selected 82 patients who accepted radical resection of esophagogastric junction carcinoma from March 2015 to March 2018 in our department, including 53 males and 29 females, aged 48-72 (61±6) years. The patients were divided into four groups according to the surgical method: a left thoracotomy group (n=14), a laparoscopic left small thoracotomy group (n=33), a thoracoscopic Ivor-Lewis group (n=17), and a thoracoscopic McKeown group (n=18). Their clinical characteristics, operative situations, postoperative complications and survival rate were analyzed. Results    Among the four groups, the left thoracotomy group cost the shortest operation time, followed by laparoscopic left small thoracotomy group, thoracoscopic McKeown group and thoracoscopic Ivor-Lewis group. The thoracoscopic McKeown group/laparoscopic left small thoracotomy group had the least bleeding. The fewest lymph nodes were dissected in the left thoracotomy group and the most in the thoracoscopic McKeown group. The laparoscopic left small thoracotomy group had the lowest total complication rate and the incidence of pneumonia and arrhythmia among the four groups (P<0.05). There was no significant difference in survival rate among the four groups (P>0.05). Conclusion    For Siewert type Ⅰ and type Ⅱ esophagogastric junction carcinoma, thoracoscopy combined with laparoscopic radical resection is safe and reliable. Laparoscopic left small thoracotomy has the advantages of minimal invasiveness and complete lymph node dissection, especially for the patients with poor cardiopulmonary function, which will significantly shorten operation time and reduce postoperative complications, so it is worth to be popularized.

Simple pulmonary artery approach in subarterial ventricular septal defect repair in 102 patients: A clinical analysis / 中国胸心血管外科临床杂志

@#Objective    To summarize and analyze the experience of subarterial ventricular septal defect (VSD) repaired with simple pulmonary artery approach. Methods    We retrospectively anlyzed the clinical data of 102 patients with subarterial VSD repaired with simple pulmonary artery approach in our hospital from August 2015 to October 2018. There were 67 males and 35 females at median age of 3 years (ranging 4 months to 49 years). Results    The median operation time was 82 (54-136) min. Median cardiopulmonary bypass time was 36 (21-62) min. The median aortic cross-clamping time was 13 (7-32) min. Thirty two patients of tracheal intubation were removed from the fast-track operating room immediately after surgery. Of the 102 patients, 67 patients underwent a small incision in the lower sternum. The median postoperative ICU stay time was 26 (13-36) h. There was no planned reoperations and no early death. Conclusion    Simple pulmonary artery approach for subarterial ventricular septal defect repair with less intracardiac procedures, short operation time, less trauma, quick postoperative recovery has certain advantages in the application of specific groups.

Cyclo-oxygenase-2 promotes migration and invasion of breast cancer MDA-MB231 cells by regulating EMT / 中国肿瘤生物治疗杂志

@#Objective:To investigate the role of cyclo-oxygenase-2 (COX-2) in breast cancer metastasis and its possible mechanism. Methods: A total of 45 cases of primary breast cancer tissues and brain metastatic breast cancer tissues were collected from patients, who underwent mastectomy in Yunnan Cancer Hospital from October 2015 to April 2018, including 30 cases of primary lesions and 15 cases of brain metastasis. qPCR was used to detect the expression of COX-2 in breast cancer tissues and brain metastatic breast cancer tissues. Recombinant viruses with COX-2 over-expression (LV6-COX2) or COX-2 knockdown (LV3-COX2 shRNA1, LV3-COX2 shRNA2) were transfected into human breast cancer MDA-MB-231 cells; After obtaining the stable expression cell lines, the effect of COX-2 expression on the proliferation of MDA-MB-231 cells was detected by CCK-8, and the effects of COX-2 expression on the migration and invasion of MDA-MB-231 cells were detected by scratch test and Transwell assay, respectively. The mRNAand protein expressions of COX-2 in each group were examined by qPCR and WB, respectively. The effect of COX-2 expression on the expression of EMT-related genes in MDA-MB-231 cells was analyzed by qPCR. Results: The expression of COX-2 in tissues of patients with brain metastases was significantly higher than that in patients with primary breast cancer tissues (P<0.01), and it was correlated with tumor TMN stage in breast cancer patients. MDA-MB-231 cell lines with stable COX-2 over-expression/knockout were successfully constructed. Over-expression of COX-2 promoted the migration and invasion of MDA-MB-231 cells (all P<0.01), and significantly increased the expressions of MMP2, MMP1, N-cadherin and vimentin (all P<0.01), but exerted insignificant effect on cell proliferation. The effect of COX-2 silence exerted the opposite effect and promoted cell proliferation (P<0.05). Conclusion: COX-2 is highly expressed in brain metastatic breast cancer tissues, which may promote the migration and invasion of breast cancer MDA-MB-231 cells by regulating EMT processes.

Mechanisms of miR-503 inhibiting radio-resistance of esophageal squamous cell carcinoma cells by targeting ERCC1 / 中国肿瘤生物治疗杂志

@# Objective: To investigate the mechanism of miR-503 modulates radio-resistance of esophageal squamous cell carcinoma (ESCC) by targeting excision-repair cross-complementing 1 (ERCC1). Methods: The expression level of miR-503 in radio-resistant ESCC tumor tissues and KYSE140 and KYSE140R cells was detected by qPCR. The miR-503 mimic, miR-503 inhibitor or si-ERCC1 was transfected into KYSE140 and KYSE140R cells.After radiation treatment, the colony formation assay and CCK-8 assay were used to detect the proliferation of KYSE140R cells. Flow cytometry was used to detect apoptosis of KYSE140R cells. WB was used to detect changes in protein expression of ERCC1. Dual luciferase reporter gene assay was used to validate the targeting relationship between miR-503 and ERCC1. Results: The expression level of miR-503 was down-regulated in radio-resistant tissues and ESCC cell lines (all P<0.01). Over-expression of miR-503 significantly inhibited cell proliferation and promoted apoptosis of KYSE140R cells (all P<0.01). Dual-luciferase reporter assay validated that ERCC1 was a target gene of miR-503, and miR-503 negatively regulated the expression of ERCC1. Over-expression of miR-503 significantly down-regulated the expression of ERCC1 in KYSE140 and KYSE140R cells (both P<0.01), inhibited cell proliferation (both P<0.01), but significantly increased apoptosis rate (all P<0.01); knockdown of ERCC1 exhibited a similar effect, while knockdown of both ERCC1 and miR-503 reversed the above effects. Conclusion: Over-expression of miR-503 up-regulated the radio-sensitivity of KYSE140R cells by targeting ERCC1.

Current status and future of adult congenital heart disease / 中国胸心血管外科临床杂志

@#Congenital heart disease refers to the structural or functional abnormality of the macrovascular in the heart or thoracic cavity caused by the failure of the formation of the heart and large blood vessels during the embryonic development or the abnormal closure of the heart or the closure of the channel after birth. In the past few years, a new and broader definition of structural heart disease has been gradually proposed. Structural heart disease narrowly refers to the pathological and physiological changes of the heart caused by abnormal anatomical structures in the heart, including congenital heart disease. A few decades ago, congenital heart disease was considered as a pediatric disease, because most patients with severe lesions rarely survive to adulthood. Due to recent advances in echocardiography, anesthesia, intensive care, percutaneous intervention, especially cardiac surgery in recent decades, the treatment and intervention strategies for congenital heart disease in children have been greatly improved, a fatal defect in childhood can now be successfully repaired or alleviated. Because of these successes, more than 90% of congenital heart disease patients are expected to survive to adulthood, which has led to emerge a new population: adult patients with congenital heart disease. Adult congenital heart disease patients are different from children. Pulmonary hypertension leads to right heart failure and eventually progresses to whole heart failure. The appearance of Eisenmenger syndrome leads to severe cyanosis and worsening of the disease. At present, the continuous development of mechanical assisted circulation support devices and heart or cardiopulmonary transplantation technology has increased the survival rate of end-stage adult congenital heart disease patients with heart failure. The high incidence of cardiovascular events in pregnant patients requires comprehensive multidisciplinary team care and early coordination planning for delivery, including early counseling for pregnancy-related risks, close monitoring of cardiac function and regular scan of fetal assessment. The prenatal and postpartum integrated diagnosis and treatment model and the development of intrauterine treatment technology reduce the incidence of congenital heart disease in adults from the source through fetal intervention. Other complications such as arrhythmia, infective endocarditis, cerebrovascular accidents, and other medical underlying metabolic diseases also challenge future diagnosis and treatment. The incidence and epidemiology of adult congenital heart disease, pulmonary hypertension and end-stage heart failure complications, as well as prenatal and postpartum integrated diagnosis and treatment and intrauterine treatment are summarized in this review.

Application of pulmonary valve reconstruction technology in right ventricular outflow tract reconstruction / 中国胸心血管外科临床杂志

@#Objective To evaluate possibility and reliability of the technique of artificial pulmonary valve reconstruction in right ventricular outflow tract reconstruction. Methods We retrospectively analyzed the clinical data of 35 patients with artificial pulmonary valve reconstruction of right ventricular outflow tract reconstruction surgery in our hospital between February 2012 and December 2016. There were 35 patients with 19 males and 16 females at age of 10 years ranged 5 months to 42 years and body weight of 26 (8–62) kg. There were 21 patients with artificial moncusp valve, 6 patients with bicuspid technology, 8 patients with comprehensive forming method. Results Average extracorporeal circulation time was 75–251 (120±37) min. Aorta blocking time was 32–185 (72±28) min. ICU stay time was 14–225 (59±51) hours. Breathing machine auxiliary time was 6–68 (24±18) hours. There were 3 early postoperative deaths. There was no death during the long term following-up time. Thirty-two patients survived with heart function of class Ⅰ in 20 patients, class Ⅱ in 10 patients, class Ⅲ in 2 patients. Conclusion In right ventricular outflow tract reconstruction using the technique of artificial pulmonary valve reconstruction in the operation, it can reduce early postoperative right ventricular volume load. To smooth out perioperative patients, the surgical technique is simple, cheap, safe, but long-term follow-up still needs further observation.

SOD mimicAEOL-10150 improve lifespan and delay brain aging via inhibition of senescence-associated secretory phenotype in SAMR1 strain / 中国药理学与毒理学杂志

OBJECTIVE To observe the anti-aging effects of SOD mimicAEOL-10150 in anti-senescence accelerated mouse resistant 1 (SAMR1) strain. METHODS The lifespan of SAMR1 mice were observed by subcutaneous injection AEOL-101502 mg·kg- 1 once a week. Morris water maze, new object recognition, nesting and forced swimming were used to observe the behavioral changes of animals. Lymphocyte subgroups and ROS were measured by Flow cytometry. The cytokines levels were determined by Luminex method. The number of DCX + neurons in brain tissue was observed by immunofluorescence. RESULTS The results showed that AEOL-10150 could prolong the mean lifespan of SAMR1 mice, but it had no obvious effect on maximal lifespan. What's more, AEOL-10150 could significantly improve the spatial learning memory of aged mice, but it could not increase the number of DCX+ neurons in the hypothalamic MBH and hippocampal DG regions. Then, we observed the effects of AEOL-10150 on peripheral blood lymphocyte subgroups and cytokines. We found that AEOL-10150 significantly modulated the lymphocyte subgroups and cytokine release. Especially, AEOL-10150 can dose-dependently inhibit plasma levels of SASP related inflammatory cytokines TNF-α and IL-17. CONCLUSION The results indicate that AEOL-10150 has anti-aging effects, and the effects are closely related to modulating immunity and inhibiting SASP production.

Effects of LW-AFC, a new formula derived from Liuwei Dihuang decoction, on intestinal microbiome in senescence-accelerated mouse prone 8 strain, a mouse model of Alzheimer disease / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effects of LW-AFC, a new formula derived from Liuwei Dihuang decoction, on gut microbiota and the behavior of learning and memory of SAMP8 mice, a mouse model of Alzheimer Disease (AD), and identify the specific intestinal microbiota correlating with cognitive ability. METHODS Morris-water maze test, novel object recognition test and shuttle-box test were conducted to observe the ability of learning and memory. 16S rRNA amplicon sequencing (Illumina, San Diego, CA, USA) was employed to investigate gut microbiota. RESULTS The treatment of LW- AFC improved cognitive impairments of SAMP8 mice, including spatial learning and memory ability, active avoidance response, and object recognition memory capability. Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units (OTUs) in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1 (SAMR1) strains, the control of SAMP8 mice. The treatment of LW- AFC altered 22 (16 increased and 6 decreased) OTUs in SAMP8 mice and among them, 15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice. We further showed that there were 7 (3 negative and 4 positive correlation) OTUs significantly correlated with all the three types of cognitive abilities, at the order level, including Bacteroidales, Clostridiales, Desulfovibrionales, CW040, and two unclassified orders. LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice. CONCLUSION The effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.

LW-AFC and its active components ameliorate corticosterone-induced long-term potentiation impairment in mice / 中国药理学与毒理学杂志

OBJECTIVE LW- AFC is extracted from the classical traditional Chinese medicinal prescription-Liuwei Dihuang Decoction. Previous studies have showed that LW-AFC could improve learning & memory ability in amny animal models. In this study, we focused on evaluating the effect of several main active components from LW-AFC (B-B; loganin, LOG; morroniside, MOR; paeoniflorin, PF and stachyose, STA) on LTP. METHODS In vivo recording of LTP was used in this study to evaluate the effects of LW-AFC and it's active components on coticorsterone (Cort) induced LTP impairment. RESULTS The results showed that LW-AFC could ameliorate Cort-induced LTP impairment. The effect of LW-AFC was abolished when the immune function was inhibited. Single administration (ig, ip, icv) of any of the components had no effect on Cort-induced LTP impairment. Consecutively intragastric admin?istration or intraperitoneal injections (chronic administration) of B-B, LOG, MOR or PF for 7 d showed protective effect on Cort-induced LTP impairment. Intragastric administration of STA for 7 d protected LTP from impairment induced by Cort, while there was little improving effect when STA was administrated via intraperitoneal injection. In addition, when the intestinal microbiota was disrupted by applying the antibiotic cocktail, STA showed little protective effect against Cort. CONCLUSION In conclusion, LW-AFC and it' s components showed positive effects against cort induced LTP impairment, it seems that all displayed protective effects via indirectly, immune modulation might be the common pathway for all components; the exact pathways are different in each component, B-B, LOG, MOR and PF could be absorbed into the bloods tream and then modulate the peripheral immune function, while STA could not be absorbed and modulates the immune function via modulating intestinal microbiota. Further studies are needed to invesgate the underlying mechanisms and the synergetic effects of all components.

LW-AFC, a new formula derived from Liuwei Dihuang decoction, ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune abnormalities in PrP-hAβPPswe/PS1ΔE9 transgenic mice / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of LW- AFC, a new formula of the main active components extracted from Liuwei Dihuang decoction, on treatment of Alzheimer disease (AD) in mouse models. METHODS After treatment LW- AFC, mice were cognitively evaluated in behavioral experiments. Neuron loss, amyloid-β(Αβ) deposition, and Αβ level were analyzed using Nissl staining, immunofluorescence, and an AlphaLISA assay, respectively. Multiplex bead analysis, a radioimmunoassay, immunochemiluminometry, and an ELISA were used to measure cytokine and hormone levels. Lymphocyte subsets were detected using flow cytometry. RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice, including the impairment of object recognition memory, spatial learning and memory, and active and passive avoidance. In addition, LW-AFC alleviated the neuron loss in the hippocampus, suppressed Αβ deposition in the brain, and reduced the concentration of Aβ1- 42 in the hippocampus and plasma of APP/PS1 mice. LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone, luteinizing hormone, and follicle- stimulating hormone in the pituitary. Moreover, LW-AFC increased CD8+CD28+T cells, and reduced CD4+CD25+Foxp3+T cells in the spleen lymphocytes, down- regulated interleukin(IL)- 1β, IL- 2, IL- 6, IL- 23, granulocyte- macrophage colony stimulating factor, and tumor necrosis factor-α and -β, and up-regulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice. CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic micevia the restoration of the NIM network to a greater extent than either memantineor donepezil, which supports the use of LW-AFC as a potential agent for AD therapy.

Pharmacological study on traditional Chinese medicine and natural product in China / 中国药理学与毒理学杂志

China is abundant in natural medicinal resources. Natural medicine (NP), especially traditional Chinese medicine (TCM), have been widely employed in prevention and treatment of diseases in China for thousands of years, which make a great contribution to health care of Chinese people and the prosperity of the Chinese nation. TCM is the excellence culture inheritance of China and a medicine system with long history, tradition and unique theory and technique. Prescriptions or formula are the main form of TCM and the compatibility and composition of them are made up following the theory of TCM among which the theory of compatibility is the essential part. Clinical application and modern pharmacological study both demonstrated that TCM prescription possesses unique effect in comparison with chemical drugs. However, the pharmacological study of TCM prescription is very difficult due to multiple herbs which contain complicated chemical components in the prescription. So, the key point for the pharmacological study of TCM prescription is to elucidate its integrative effect and the mechanism of action. In recent years, great advances have been achieved in the research on TCM prescription and modern study of TCM prescription, including pharmacological and chemical studies, has becoming a hot research field in China. The pharmacological studies of TCM and NP are conducted with different ways and methods including holistic approaches in various experimental model animals and in vitro experiments in tissue, organ and cell models. In addition, a lot of new technics and methods such as″ omics″ technologies were employed in the molecular level studies, for example, researches on the mechanism of action of TCM and NP. In addition, a lot of new drugs have been developed from TCM prescriptions in China. The classical preparations of TCM, including decoction, pill, powder, ointment and pellet, etc, are prepared with traditional methods. While, the new preparations are similar to modern pharmaceutical preparations such as tablet, capsule, oral liquid, even injection and manufactured under the condition of modern pharmaceutical industry according to the requirements of GMP. To elucidate the activity mechanism and the active fractions or components are very important basis for the development of new drugs from TCM prescription. Although pharmacological study of TCM has made great progresses, it is still a great challenge to elucidate the active components and the mechanism of action of TCM prescription due to the complexity of the prescription. However, with the rapid development of science and technology and their continuous application in this research field, the pharmacological study on TCM prescription has been progressing and getting deeper rapidly.

Berberine exerts pro-apoptotic effects on PC-9 cells via activation of JNK/FOXO3 signaling / 中国肿瘤临床

Objective:To investigate the pro-apoptotic effect of berberine (Ber) on human lung adenocarcinoma PC-9 cell line, and to detect the role of c-Jun N-terminal kinase (JNK)/forkhead box protein O3 (FOXO3) signaling in this process. Methods:The PC-9 cells were randomly divided into the control group and the Ber group, which was treated with 30 and 60μM Ber. The survival rate, apoptot-ic rate, ROS generation, caspase-3 activity, and mitochondrial membrane potential of cells were detected. Western blot was per-formed to detect the expression of JNK/FOXO3 signaling and apoptosis-related proteins. A JNK-specific activation inhibitor, SP600125, was used to block the phosphorylation of FOXO3 in PC-9 cells, and then treated with Ber (30 and 60μM) for further detection after 24 h. Results:Ber treatment resulted in an obvious reduction in cell viability, promotion of cell apoptosis, downregulation of mitochondri-al membrane potential, and an increase of ROS and caspase-3 in a dose-dependent manner. Western blot analysis demonstrated that Ber treatment resulted in a significant upregulation of p-JNK, FOXO3, and Bax expression, and a downregulation of p-FOXO3 and Bcl2 levels. Moreover, the inhibition of JNK activation by SP600125 antagonized the anti-FOXO3 phosphorylation role and the pro-apoptotic role of Ber on PC-9 cells. Conclusion:Ber treatment effectively inhibits the viability of PC-9 cells and enhances apoptosis and oxidative stress injury, which may be related to the upregulation of p-JNK and FOXO3 and the downregulation of p-FOXO3.

Berberine exerts pro-apoptotic effects on PC-9 cells via activation of JNK/FOXO3 signaling / 中国肿瘤临床

Objective:To investigate the pro-apoptotic effect of berberine (Ber) on human lung adenocarcinoma PC-9 cell line, and to detect the role of c-Jun N-terminal kinase (JNK)/forkhead box protein O3 (FOXO3) signaling in this process. Methods:The PC-9 cells were randomly divided into the control group and the Ber group, which was treated with 30 and 60μM Ber. The survival rate, apoptot-ic rate, ROS generation, caspase-3 activity, and mitochondrial membrane potential of cells were detected. Western blot was per-formed to detect the expression of JNK/FOXO3 signaling and apoptosis-related proteins. A JNK-specific activation inhibitor, SP600125, was used to block the phosphorylation of FOXO3 in PC-9 cells, and then treated with Ber (30 and 60μM) for further detection after 24 h. Results:Ber treatment resulted in an obvious reduction in cell viability, promotion of cell apoptosis, downregulation of mitochondri-al membrane potential, and an increase of ROS and caspase-3 in a dose-dependent manner. Western blot analysis demonstrated that Ber treatment resulted in a significant upregulation of p-JNK, FOXO3, and Bax expression, and a downregulation of p-FOXO3 and Bcl2 levels. Moreover, the inhibition of JNK activation by SP600125 antagonized the anti-FOXO3 phosphorylation role and the pro-apoptotic role of Ber on PC-9 cells. Conclusion:Ber treatment effectively inhibits the viability of PC-9 cells and enhances apoptosis and oxidative stress injury, which may be related to the upregulation of p-JNK and FOXO3 and the downregulation of p-FOXO3.