ObjectiveTo investigate the therapeutic effect of Ganmai Dazao Tang on breast cancer-related depression and explore the mechanism of the decoction in regulating immune inflammation and neurotransmitters via the mitogen-activated protein kinase （MAPK）/nuclear factor-κB （NF-κB） pathway. MethodBALB/c mice were randomized into control， model， fluoxetine （5 mg·kg^-1·d^-1）， and low- and high-dose （crude drug 20 and 40 g·kg^-1， respectively） Ganmai Dazao Tang groups （n=10）. The mouse model of 4T1 orthotopic transplantation-induced breast cancer-related depression-like behavior was established. The depression-like behavior of mice was assessed by the tail suspension test and the forced swimming test. RT-qPCR was employed to determine the mRNA levels of interleukin （IL）-17A， forkhead box P3 （FoxP3），IL-1β， IL-6， and tumor necrosis factor-α （TNF-α） in the cerebral cortex. Flow cytometry was employed to measure the proportions of immune cell subsets in the spleen and thymus. HPLC-MS/MS was employed to measure neurotransmitter levels in the cerebral cortex. Western blotting was employed to detect the activation of the MAPK/NF-κB pathway. ResultCompared with the model group， administration of Ganmai Dazao Tang at a dose of 40 g crude drug·kg^-1 continuously for 4 weeks shortened the immobility time of modeled mice in the tail suspension and forced swimming tests （P<0.05）， down-regulated the mRNA levels of IL-1β， IL-17A， and TNF-α （P<0.05）， increased the proportions of T cells， CD4⁺ T cells， B cells， helper T 17 （Th17） cells， and regulatory T （Treg） cells， and reduced the proportion of CD8⁺ T cells （P<0.05）. Furthermore， it lowered the levels of 5-hydroxyindoleacetic acid （5-HIAA） and kynurenine （Kyn）， decreased the kynurenine/tryptophan （Kyn/Trp） ratio （P<0.05）， increased the content of 5-hydroxytryptamine （5-HT）， and down-regulated the protein levels of phosphorylated extracellular signal-regulated kinase （p-ERK）， phosphorylated p38 MAPK， and phosphorylated nuclear factor-κB p65 （P<0.05）. ConclusionGanmai Dazao Tang can down-regulate the expression of inflammatory cytokines such as IL-1β， IL-17A， and TNF-α， restore 5-HT metabolism and Kyn/Trp balance， increase the 5-HT content， and reduce the activation of p38 MAPK， ERK， and the MAPK-mediated NF-κB signaling pathway to reduce neuroinflammation in the treatment of cancer-related depression.

Objectives:To explore the effects of interatrial shunt on cardiac function and clinical prognosis of patients with heart failure with reduced ejection fraction(HFrEF). Methods:This study was a prospective single-arm study.From December 2021 to December 2022,15 consecutive patients with HFrEF from Beijing Anzhen Hospital were enrolled in this study.Interatrial shunt was performed with a D-Shant atrial shunt device.Right heart catheterization was performed before and immediately after device implantation,pulmonary capillary wedge pressure(PCWP),mean right atrial pressure(RAP),interatrial gradient pressure,mean pulmonary artery pressure,total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),cardiac index(CI),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured.Patients were followed-up for 12 months after procedure,changes in cardiac structure and function were evaluated by echocardiography.NYHA classification,6-minute walking distance(6MWD),and Kansas City cardiomyopathy questionnaire(KCCQ)were observed.All-cause mortality and rehospitalization for heart failure served as clinical endpoints. Results:Interatrial shunt procedure was successful in all patients.Compared with preoperative value,PCWP,interatrial gradient pressure,mean pulmonary artery pressure,and TPR were significantly decreased,while Qp/Qs was significantly increased immediately after procedure(all P<0.01).There were no significant changes in RAP,PVR,and CI post procedure(all P>0.05).There were no significant differences in shunt size,shunt velocity,and shunt pressure difference between postoperative immediately and at 12-months follow-up(all P>0.05).At 12 months,left ventricular ejection fraction was significantly higher than baseline level(P<0.05),and there were no significant changes in right atrial diameter and right ventricular fractional area change(both P>0.05).Compared with preoperative status,NYHA classification was improved,KCCQ score was increased,and the number of patients with 6MWD>450 m was increased at 12 months(all P<0.05).N-terminal pro-B-type natriuretic peptide value was significantly decreased at 12 months(P<0.05).No patient died during the 12-months follow-up period,and there were no device-related adverse events.Two patients experienced hospital readmission for heart failure. Conclusions:Implantation of interatrial shunt device could effectively improve hemodynamic parameters in patients with HFrEF and is related to significantly improved cardiac function at 12-months follow-up.

Objective: To explore the therapeutic effects of ginseng total saponins (GTSs) on cognitive impairments in astronauts caused by prolonged exposure to microgravity environment. Methods: Fifty specific pathogen-free (SPF) male Wistar rats were randomized into control, hindlimb suspension (HLS), Huperzine A (HLS-Hup A 0.1 mg/kg), low-dose GTSs (HLS-GTSs 100 mg/kg), and high-dose GTSs (HLS-GTSs 200 mg/kg) groups, based on the completion time of reward-directed conditioning tasks. Except for rats in the control group, the others were subjected to HLS and treated with drugs (day 20 – 58), received reflex test under the condition of rewarding, and underwent Nissl body staining and Western blot detection on hippocampal. Results: After modeling, rats in HLS group exhibited a reduction in the number of lever presses and an increase in the completion time of the reward-directed operant conditioning task Ⅰ (P < 0.05) when compared with the control group, which were not substantially altered in the HLS-GTSs 100 and 200 mg/kg groups (P > 0.05). In the reward-directed operant conditioning task Ⅱ, the HLS group rats demonstrated a marked decrease in the number of lever presses (P < 0.05) and nose pokes (P < 0.01) when compared with the control group rats; the HLS-GTSs 100 mg/kg showed a significant increase in the number of lever presses and nose pokes (P < 0.05), while the HLS-GTSs 200 mg/kg demonstrated a significant reduction in completion time and an elevation in the number of lever presses (P < 0.05) when compared with the HLS group rats. In visual signal discrimination task, compared with the control group rats, the HLS group rats showed decrease in the indexes of the visual signal discrimination(P < 0.01), while HLS-GTSs 100 and 200 mg/kg groups exhibited manifest increase in it (P < 0.01). In reward extinction experiment, the number of lever presses in HLS rats significantly increased when compared with the control group (P < 0.01); compared with the HLS group, HLS-GTSs 100 and 200 mg/kg groups demonstrated a marked descrease (P < 0.05). The expressions of N-methyl-D-aspartic acid receptor 1 (NR1) and phosophorylated N-methyl-Daspartic acid receptor 2B (p-NR2B) proteins were markedly decreased in rats in the HLS group (P < 0.05 and P < 0.01, respectively), while that of NR2B protein maintained the same (P > 0.05). GTSs increased the expression levels of p-NR2B (P < 0.01). Conclusion GTSs improved the learning and memory ability of complex operations by regulating the NR1/NR2B phosphorylation pathways in rats.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

OBJECTIVE: To observe the effect of luteolin on the proliferation and expression of OPCML in breast cancer cell line MDA-MB-231. METHODS: Cultured MDA-MB-231 cells were treated with luteolin at the concentrations of 5, 10 and 20 μmol/L for 24 or 48 h. MTT assay was used to detect cell proliferation and flow cytometry was used to detect the cell apoptosis. The expressions of OPCML mRNA and protein were detected using real-time quantitative PCR and Western blotting, respectively. OPCML gene methylation in the promoter region was detected using methylation-specific PCR (MSP), and the activity of methylase in the cells was analyzed. RESULTS: MTT assay showed that treatment with luteolin at 5, 10 and 20 μmol/L for 24 h concentration-dependently decreased the viability of MDA-MB-231 cells ( < 0.05). Flow cytometry also showed that luteolin at different concentrations could induce apoptosis of MDA-MB-231 cells ( < 0.05). Luteolin dose-dependently induced the expression of OPCML mRNA and protein in MDA-MB-231 cells ( < 0.05), down-regulated the methylation status in the promoter region of OPCML gene, up-regulated the level of non-methylated OPCML, and reduced the activity of methylase in the cells ( < 0.05). CONCLUSIONS Luteolin inhibits the proliferation of MDA-MB-231 breast cancer cells probably by upregulating OPCML expression and its demethylation.
Apoptosis ; Breast Neoplasms ; Cell Adhesion Molecules ; Cell Line, Tumor ; Cell Proliferation ; GPI-Linked Proteins ; Humans ; Luteolin

Objective To observe the regulation of microRNA (miRNA,miR)-758-3p on the expression of murine double microsomal gene 2 (MDM2) and its effect on invasion and proliferation of gastric cancer cell line MGC803.Methods The bioinformatics software was used to predict MDM2 as target gene of miR-758-3p.The wild type MDM2 gene 3'untranslated region luciferase reporter gene vector and miR-758-3p target sequence mutated vector and the corresponding miRNA were transfected into gastric cancer cells MGC803 by lipofectamine.Dual luciferase reporter system detects luciferase activity.The miR-758-3p mimics were transfected into gastric cancer cell MGC803 by lipofectamine.Real-time PCR was used to detect the transfection efficiency.Real-time PCR and Western blot were used to detect miR-MDM2 expression level in cells after transfection.Transwell assay and CCK-8 assay were used to detect cell invasion and proliferation.SPSS 20.0 was used to conduct the statistical analysis.Results Dual luciferase reporter assay confirmed that miR-758-3p could target MDM2 gene(P ＜ 0.05).The expression level of miR-758-3p in MGC803 cells transfected with miR-758-3p mimics was significantly higher than that in miR-NC cells [(6.68 ±0.53) vs (0.84 t0.12),P ＜0.01].Compared with miR-NC group,MDM2 expression was down-regulated in MGC803 cells transfected with miR-758-3p mimics (P ＜ 0.05).The number of invasive cells in miR-NC group and miR-758-3p group were (136.00 ± 16.62) and (79.49 ± 6.42).After knockdown MDM2,the invasiveness of cells was significantly decreased (P ＜ 0.05).The results of CCK-8 showed that the proliferation of MGC803 cells transfected with miR-758-3p group was significantly lower than that of miR-NC group (P ＜ 0.01).Conclusion miR-758-3p can reduce the invasion and proliferation of MGC803 cells by targeting MDM2.

Objective In view of the controversy over radiotherapy target volume for patients with limited-stage small cell lung cancer ( SCLC), a prospective randomized controlled trial was conducted to compare the impact of different radiotherapy target volumes on prognosis. Methods After 2 cycles of EP chemotherapy,patients without progressive disease were randomly assigned to receive thoracic radiotherapy (TRT) to either the post-or pre-chemotherapy primary tumour extent as study arm or control. Involved field radiotherapy (IFRT) to the entire metastatic lymph node regions was applied for both arms. TRT consisted of 45 Gy/30Fx/19 d administered concurrently with cycle 3 chemotherapy. Prophylactic cranial irradiation was administered to patients achieved complete or partial remission. Kaplan-Meier method was used for survival analysis. Results Between June 2002 and December 2017,159 and 150 patients were randomly assigned to study arm and control respectively. The 1-,2-,and 5-year local/regional control rates were 79. 4%,61. 5% and 60. 1% respectively in the study arm versus 79. 8%,66. 5%,and 57. 3% in the control arm (P=0. 73). The median OS time was 22. 1 months in the study arm (95%CI,18. 2-26. 0 months) and 26. 9 months (95%CI,23. 5-30. 3 months) in the control arm,the 1-,3-,5-,and 7-year OS rates were 81. 1%,31. 6%, 23. 9% and 22. 2% respectively in the study arm versus 85. 3%,36. 6%,26. 1% and 20. 0% in the control arm (P=0. 51).Grade 2-3 acute esophagitis was developed in 32. 9% and 43. 2% of patients respectively in study arm and control arm (P=0. 01),while grade 2-3 pulmonary fibrosis was observed in 2. 0% and 10. 9% of patients ( P= 0. 01 ) respectively. Conclusions For patients with limited-stage SCLC who received induction chemotherapy,thoracic radiotherapy can be limited to post-chemotherapy tumour extent and IFRT can be routinely applied.

Objective To investigate the relationship between different brain developmental stages and changes of cognitive function in rats. Methods 1-month, 2-month and 8-month-old rats were selected to imitate the juvenile, adolescent and adulthood, respectively, and their behavioral functions were compared. The reward operant conditioning and Morris water maze task were used to investigate the differences in exploration interest, executive and recognition ability, spatial learning and memory of the rats at different ages. Results In the reward operant conditioning and Morris water maze task, there was no significant difference in the cognitive function between 1-month and 2-month-old rats. In the reward conditioning phase, the nose pokes numbers of 8-month-old rats were significantly decreased compared with the 1-month-old rats (P＜ 0. 01). There was no significant difference in nose pokes accuracy. During the operant conditioning phase, the lever press numbers and accuracy of 8-month-old rats were significantly decreased ( P ＜ 0. 05 or P ＜ 0. 01) and the press latency was longer (P ＜ 0. 05). At the phase of visual identification, the press and reward numbers, and the visual identification index were significantly decreased ( P ＜ 0. 05 or P ＜ 0. 01). In the Morris water maze test, compared with the 1-month-old rats, the total swimming distance and escape latency of the 8-month-old rats were significantly increased (P＜ 0. 05), as well as average swimming speed ( P ＜ 0. 05 or P ＜ 0. 01) in spatial learning phage. In spatial memory phage, the swimming distance and time spent in the target quadrant were obviously decreased (P＜ 0. 01). Conclusions The cognitive functions of rats at different brain developmental stages are different. The juvenile and adolescent rats have similar cognitive functions, but 8-month-old adult rats appear decline in the exploration interest, executive and recognition ability, and spatial learning and memory function.

Objective To study the effects of different color light stimulus, duration of stimulus and day/night training on the incentive conditioned reflex of rats,and to provide a data basis for the methodology of incentive conditional reflection experiments. Methods Three experiments were included in this study. During the experiment 1, a total of 30 male 8-week-old Wistar rats were divided into three groups:red light stimulation group,yellow light stimulation group and blue light stimulation group. During the experiment 2, a total of 32 male 8-week-old Wistar rats were divided into three groups:the group I(with a light stimulation duration of 10 s), the group II(with a light stimulation duration of 30 s), and the group III(with a light stimulation duration of 60 s). During the experiment 3,a total of 16 male 8-week-old Wistar rats were randomly divided into two groups,of which the first group was trained at 9:00 a.m. every day, and the second group was trained at 21:00 every day. All the laboratory animals were given reward conditioned reflex training, and indicators such as the number of correct nose pokes,the number of incorrect nose pokes,the ratio of correct nose pokes and so on were counted and calculated. Results During the experiment 1,there was no significant difference in the numbers of correct nose pokes and incorrect nose pokes,movement distances and average speeds of the rats among the three groups. During the experiment 2,compared with the group with a light duration of 10 s,the rats in the groups with a light duration of 30 s or 60 s had a higher number of correct nose pokes(P< 0.05). Moreover,on the 13th and 14th days,the ratio of correct nose pokes of the group with a light duration of 30 s was significantly higher than that of the group with a light duration of 10 s(P< 0.001). During the experiment 3,there were no significant differences in the number of correct nose pokes and the nose poke accuracy of the rats between the two groups. Conclusions In the reward conditioned reflex test, red,yellow and blue light stimuli have similar reward prediction effect. When stimulated with the same light, the time of stimulation has an impact on the learning ability of the rats,and an appropriate extension of stimulation is beneficial to the formation of conditioned reflex in them. The day/night training has no effect on the learning and memory ability of the rats.

Objective To develop a multi-mode,detailed and sensitive object recognition method for learning and memory research,including novel object recognition task,object location recognition task,temporal order memory task and object context recognition task in animals based on their spontaneous behavior. Methods Two strains of mice(KM and ICR)and four patterns were used to establish the object recognition method and several relative factors,such as time of test phase,delay between test phase and familiar phase were investigated. Results It was stable and reasonable to set the time of familiar phase as 5 min,the interval between test phase and familiar phase as 10 min,and the time of test phase as 3-5 min,under the precondition of habituation for three days and selecting the appropriate object pairs. Conclusions Object recognition test including four patterns has been systematically established as a stable, reliable and normative way for the research of animal learning and memory and drug development.