Vein graft (VG) failure (VGF) is associated with VG intimal hyperplasia, which is characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs). Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition, also known as dedifferentiation. There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation, exerting vasoprotective functions; however, the precise mechanisms have not been fully characterized. Therefore, we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation. Ginger significantly inhibited neointimal hyperplasia and promoted lumen (L) opening in a 3-month VG, which was primarily achieved by reducing ferroptotic stress. Ferroptotic stress is a pro-ferroptotic state. Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type, forming neointima (NI) after vein transplantation. Ginger and its two main vasoprotective ingredients (6-gingerol and 6-shogaol) inhibit VSMC dedifferentiation by reducing ferroptotic stress. Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53, while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase (Alox5), both promoting ferroptosis. Furthermore, both ingredients co-target peroxisome proliferator-activated receptor gamma (PPARγ), decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) expression. Nox1 promotes intracellular reactive oxygen species (ROS) production and directly induces VSMC dedifferentiation. In addition, Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production, indirectly leading to VSMC dedifferentiation. Ginger, a natural multi-targeted ferroptotic stress inhibitor, finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.

ObjectiveTo explore the establishment and evaluation methods of the rat model of acute myocardial infarction （AMI） in coronary heart disease with the syndrome of Qi and Yin deficiency by sleep deprivation （SD） combined with isoproterenol （ISO） and preliminarily explore its biological basis. MethodForty SD rats were assigned into normal （no treatment）， SD （treatment in modified multi-platform water environment for 96 h）， ISO （subcutaneous injection of ISO at 100 mg·kg^-1 once every other day for a total of 2 times）， and SD+ISO （injection of 100 mg·kg^-1 ISO after SD for 72 h and 96 h） groups. The cardiac function was detected by small animal echocardiography. The serum levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， and cardiac troponin T （cTnT） were measured by biochemical methods. The pathological changes of the myocardial tissue were observed by hematoxylin-eosin staining. The general state， body weight， grip strength， body temperature， behaviors in open field test， serum levels of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， cAMP/cGMP ratio， red （R）， green （G）， blue （B） values of the tongue surface， and pulse amplitude were observed and measured to evaluate the modeling results. Enzyme-linked immunosorbent assay was employed to determine the serum levels of interleukin-18 （IL-18）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， malondialdehyde （MDA）， corticotropin-releasing factor （CRF）， adrenocorticotropic hormone （ACTH）， triiodothyronine （T3）， tetraiodothyronine （T4）， cluster of differentiation 4 （CD4）， and cluster of differentiation 8 （CD8）. ResultIn terms of disease indicators， the ISO and SD+ISO groups had lower cardiac function indicators than the normal group （P<0.01）. The levels of CK， CM-MB， LDH and cTnT elevated in each model group compared with the normal group （P<0.01）. The pathological changes of myocardial tissue were obvious in the ISO and SD+ISO groups. In terms of syndrome indicators， compared with the normal group， the SD and SD+ISO groups showed decreased body weight at each time point （P<0.01）， and the ISO group showed decreased body weight at the time points of 48 h and 72 h （P<0.05， P<0.01）. The paw temperature and rectal temperature increased in the SD group （P<0.01）. The model groups showed weakened grasp strength， lowered R， G， and B values of the tongue surface （P<0.01）， prolonged immobility time （P<0.01）， reduced total distance and number of entering the central area （P<0.01）， decreased average speed （P<0.05， P<0.01）， and increased cAMP and cGMP （P<0.05， P<0.01）. The cAMP/cGMP ratio was increased in the SD+ISO group （P<0.01）， and the pulse amplitude was decreased in the SD and SD+ISO groups （P<0.01）. In terms of serological indicators，compared with the normal group， the levels of IL-18， TNF-α， SOD and MDA were significantly increased in the ISO and SD+ISO groups （P<0.01）， the CRF， ACTH， CORT， T3， T4， CD4 and CD8 in the model groups were increased （P<0.05， P<0.01）. ConclusionSleep deprivation for 96 h combined with high-dose ISO can successfully establish a rat model of acute myocardial infarction in coronary heart disease with the syndrome of Qi and Yin deficiency. The model evaluation system can be built with disease indicators of western medicine， histopathological indicators， macroscopic indicators of traditional Chinese medicine， and serological indicators.

Objective:To investigate the anti-inflammatory and analgesic effects of Zhonghua Dieda Pills; To preliminarily explore its mechanism on adjuvant arthritis model rats.Methods:Three inflammatory models and two pain models were used to investigate the anti-inflammatory and analgesic effects of Zhonghua Dieda Pills. After establishing the adjuvant arthritis rat model, the rats were divided into normal group, model group, dexamethasone group (0.8 mg/kg), and Zhonghua Dieda Pills (2.0, 1.0, 0.5 g/kg) groups according to random number table method. Each group was given corresponding drugs once a day for 5 weeks. The toe volume was measured at 1, 3 and 5 weeks after administration, and the swelling degree was calculated; the organ indices of rats were calculated and the histopathological changes of articular cartilage were observed by HE staining; the expressions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in joint tissues were detected by immunohistochemistry.Results:Zhonghua Dieda Pills (2.0 g/kg) group significantly reduced the swelling of foot and plantar of rats, reduced the swelling of ear of mice, and reduced the dry weight of granuloma of rats ( P<0.05); Zhonghua Dieda Pills (1.4 g/kg) group significantly reduced the number of twisting of rats, and the pain threshold after 3 h of administration was significantly higher than that of the control group ( P<0.05); Zhonghua Dieda Pills (2.0 g/kg) group significantly reduced the swelling of the foot and metatarsal of arthritic rats after 3-5 weeks of administration ( P<0.05), decreased the thymus index ( P<0.05), and reduced the expression levels of IL-1β, TNF-α and TGF-β in joint tissues ( P<0.05). Conclusion:Zhonghua Dieda Pills have confirmed anti-inflammatory and analgesic effects, which may play a therapeutic role in adjuvant arthritis model rats by reducing the levels of inflammatory factors such as IL-1β, TNF-α and TGF-β.

ObjectiveTo collect common prescriptions from multiple channels based on the mainstream guidance materials combined with ancient books to provide references for the selection principles of common prescriptions in clinical practice guidelines of traditional Chinese medicine （TCM） and western medicine. MethodWith the research on the selection of commonly used prescriptions in Clinical Practice Guidelines of Chinese and Western Medicine for Cough in Children as an example，the nation-recommended Schedule Ⅲ drugs and prescriptions for cough in children in the clinical diagnosis and treatment guidelines of TCM （TCM and western medicine）/expert consensus/clinical pathway/diagnosis and treatment protocols，three TCM pediatric textbooks， the experience of famous experts， and ancient books were searched for the establishment of a prescription database and analysis of medication regularity. ResultThe results showed that there were 71 commonly used prescriptions for the treatment of cough in children. The top 3 clinically indicated syndromes were the syndrome of phlegm-heat blocking the lung，the syndrome of wind-heat invading the lung，and the syndrome of wind-cold attacking the lung，and the top 5 efficacies corresponding to high-frequency drugs were reliving cough and dyspnea， clearing heat/resolving phlegm， dispersing wind/dissipating cold， clearing heat/purging fire， and dispersing wind/dissipating heat. The most commonly used Chinese medicines included Armeniacae Semen Amarum， Platycodonis Radix， Bolbostemmatis Rhizoma， Ephedrae Herba， Scutellariae Radix， Pinelliae Rhizoma， and Citri Reticulatae Pericarpium. Some drugs showed high internal correlations with Armeniacae Semen Amarum and Platycodonis Radix. There were 228 prescriptions for the treatment of cough in children based on the ancient books in the Chinese Medical Code. The most commonly used Chinese medicines were Pinelliae Rhizoma， Armeniacae Semen Amarum， Ginseng Radix et Rhizoma， Poria， Citri Reticulatae Pericarpium， Platycodonis Radix， Zingiberis Rhizoma Recens， and Bolbostemmatis Rhizoma. The top 5 efficacies corresponding to high-frequency drugs were dispersing wind/dissipating cold， relieving cough and dyspnea， clearing heat/resolving phlegm， warming cold/resolving phlegm， and tonifying Qi. Some drugs showed high internal correlations with Pinelliae Rhizoma and Platycodonis Radix. As revealed by the comparison of ancient and modern medication， the medication principles could be roughly classified into two categories： ventilating the lung/descending Qi and resolving phlegm. In ancient medication， the drugs for cough in children were mainly used for warming， tonifying， dissipating cold， excreting water， alleviating edema， and astringing lung and intestines， while in modern medication， the prescriptions were mainly for dispersing wind， clearing heat， tonifying yin， and moistening dampness. ConclusionThis study systematically analyzed the commonly used prescriptions for the treatment of cough in children and provided references for the selection of TCM in clinical practice guidelines.

Objective: To understand the epidemic status and influencing factors of Mongolian children with ASD in central and eastern Inner Mongolia, so as to provide data support for formulating prevention and intervention strategies and improving the overall epidemiological investigation of ASD in Inner Mongolia. Methods: Sixteen kindergartens and primary schools were selected from Chifeng City, Ulanqab City, Tongliao City, Hulunbuir City and Xilingol League cities in Inner Mongolia by means of random cluster sampling. Firstly, 7 108 children aged 3-14 were initially screened with the Kirschner Autism Behavior Scale(CABS), and then the children with ASD positive were given the autism behavior test scale (ABC). According to the diagnostic criteria, the professionals, including chief physicians and associate chief physicians from the major of child psychiatry, diagnosed ASD with the total score of ABC scale ≥62. Univariate and Logistic regression multivariate analysis were carried out among Mongolian children to find out the influencing factors related to the occurrence of Mongolian ASD in Inner Mongolia. Results: The prevalence of Mongolian children was 0.37%. Mongolian ASD group and Mongolian normal children series in the household register, habitual twitch, hyperactivity, bite lips, families have extreme introverts, mothers age, father s cultural level, cultural degree of mother, father mother mild character, irritable, neonatal diseases, fetal gestational age distribution had statistical significance( χ 2/Z= 12.58 , 16.68, 14.93, 64.43, -3.76, -2.86, 4.57, 11.12, 12.33, 16.66, P <0.05). Conclusion Measures such as shaping a healthy growth environment, adjusting parental style, paying attention to the level of early childhood language development, and preventing neonatal diseases might lower the risk of ASD in children.

Objective: To understand the prevalence and influencing factors of children with ASD in central and eastern Inner Mongolia, and to provide theoretical basis for disease prevention and prevalence of ASD. Methods: Sixteen primary schools and kindergartens were selected from 5 cities in central and eastern Inner Mongolia through random cluster sampling. A total of 15 817 children aged 3-14 years were selected. Children who were positive using Clancy Autism Behavior Scale were further diagnosed according to the teacher s nomination form and the Autism Behavior Checklist, as well as the diagnostic criteria of the fifth edition of the American Diagnostic & Statistical Manual of Mental Disorders by 2 professionals. Results: The prevalence of ASD was 0.27% (42/15 817), with prevalence in urban areas (0.16%, 15/9 231) higher than that of rural areas (0.41%, 27/6 586) ( χ 2=8.89, P <0.01). Logistic regression analysis showed that maternal education and language development were negatively associated with ASD in urban children [ OR =0.29(95% CI =0.12-0.69) and 0.18(95% CI =0.05-0.60), P <0.05]. ASD in rural children were positively associated with enuresis and introverted family members [ OR =7.09(95% CI =1.60-32.27) and 8.63(95% CI =3.10- 24.01 ), P <0.05]. Conclusion High prevalence of ASD is found in urban area of central and eastern Inner Mongolia. Unhealthy habits, neonatal diseases, low parental education, delayed language development and poor exercise performance are primary factors associated with ASD in both urban and rural areas.

Objective To investigate the intervention effect of Xuebijing Injection on the differentiation of bone marrow hematopoietic stem cells (HSC) in septic mice. Methods Fifty-four male C57BL/6N mice were randomly divided into three groups: normal control group, model group and Xuebijing group, each group with 18 mice. The mouse models of sepsis were duplicated by intra-peritoneal injection of 10 mg/kg E. coli lipopolysaccharide (LPS) method. Starting from the day of modeling, Xuebijing Injection 20 mL/kg was intravenously injected into the tail vein in Xuebijing group, once a day for consecutive 4 days; the normal control and model groups were intravenously injected with normal saline at the same dose and site for 4 days. The bone marrow cells of the femur and tibia of the mice were isolated after 4 days of various treatments in the three groups, and the proportions of bone marrow HSC Lin-Sca-1+c-Kit+ (LSK) and hematopoietic progenitor cells Lin-Sca-1-c-Kit+ (LS-K) of each group were detected by flow cytometry. Results Finally, 14 mice were included in the normal control group, 17 in the model group, and 12 in the Xuebijing group. With the prolongation of time, the body weight of the normal control group gradually increased, the body masses of the model group and the Xuebijing group were decreased first and then increased, reaching a peak at 96 hours after the model was established, but they were still significantly lower than the body mass of normal control group (g: 19.81±0.27, 19.58±0.39 vs. 22.23±0.30, both P < 0.05). Compared with the normal control group, the proportions of LSK, LS-K, long-term HSC (LT-HSC), and megakaryocyte-erythroid progenitor cells (MEP) were all significantly increased in the model group [LSK: (16.62±1.28)% vs. (12.89±0.83)%, LS-K: (44.77±1.77)% vs. (30.34±0.90)%, LT-HSC: (6.88±0.48)% vs. (1.83±0.24)%, MEP: (13.89±1.26)% vs. (9.38±0.66)%, all P < 0.05], the proportion of multipotential progenitor cells (MPP) was significantly decreased [(2.41±0.34)% vs. (5.99±0.59)%, P < 0.05]. Compared with the model group, the LSK and myeloid progenitor (CMP) of the Xuebijing group were significantly reduced [LSK: (12.25±0.69)% vs. (16.62±1.28)%, CMP :(0.31±0.05)% vs. (0.55±0.13)%, both P < 0.05], and LS-K, LT-HSC, MEP showed a decreasing trend [LS-K: (42.75±2.48)% vs. (44.77±1.77)%, LT-HSC:(5.98±0.70)% vs. (6.88±0.48)%, MEP: (10.94±1.36)% vs. (13.89±1.26) %], but the differences were not statistically significant (all P > 0.05). There were no significant differences in the proportions of short-term HSC (ST-HSC) and granulocyte-macrophage progenitor cells (GMP) among the three septic groups (all P > 0.05). Conclusion Xuebijing Injection can improve the differentiation function of bone marrow cells in septic mice, which may be possibly related to the inhibition of pathological proliferation of bone marrow hematopoietic stem cells and progenitor cells in septic mice by Xuebijing Injection.

OBJECTIVE: To investigate the effect of 1,2-dichloroethane(1,2-DCE) acute inhalation exposure on the differential gene expression of phase Ⅰ metabolic enzymes. METHODS: The specific pathogen free SD rats were randomly divided into control group(16 rats), low-and high-dose groups(24 rats in each group, half males and half females). Low-and high-dose group were given daily 600, 1 800 mg/m~(3 ) of 1,2-DCE, and the control group given the fresh air by dynamic inhalation for 8 hours per day for consecutive 7 days. After the end of exposure, the relative mRNA expression of cytochrome P450 2 E1(CYP2 E1), alcohol dehydrogenase(ADH1) and acetaldehyde dehydrogenase 3 alpha 1(ALDH3α1) in the liver tissue was detected by real-time fluorescence quantitative polymerase chain reaction. RESULTS: The relative expression of CYP2 E1 in male high-dose group was higher than that in male low-dose group and female high-dose group(P<0.05). The relative expression of ADH1 in male low-and high-dose groups was higher than that in male control group(P<0.05). The relative expression of ADH1 in male high-dose group was higher than that in male low-dose group and female high-dose group(P<0.05). The relative expression of ALDH3α1 in high-dose group was higher than that in control group and low-dose group(P<0.05). CONCLUSION: High dose 1,2-DCE could increase the gene expression of phase Ⅰ metabolic enzymes in rat liver. The 1,2-DCE has more obvious effect in male rats than in female rats.

Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-1/PD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural information will benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.
Antibodies, Monoclonal ; immunology ; therapeutic use ; Antibodies, Monoclonal, Humanized ; immunology ; therapeutic use ; B7-H1 Antigen ; antagonists & inhibitors ; immunology ; Humans ; Neoplasms ; drug therapy ; immunology ; pathology ; Programmed Cell Death 1 Receptor ; antagonists & inhibitors ; immunology ; Signal Transduction ; drug effects ; immunology ; T-Lymphocytes ; immunology

Objective The aim of this study was to investigate the distribution and clinical significance of CD8+ T cells in bladder cancer tissues in situ.Methods Immunohistochemistry were used to examine the distribution of CD8+ T cells in bladder cancer tissues,which were obtained from January 2003 to December 2009 from 302 patients.Among all the patients,262 were male while 40 were female;mean age is 60 years;tumor size ≤ 3 cm was in 235 and tumor size ＞ 3 cm was in 67;Unifocal tumor was in 214 and multifocal tumors were in 88.Amount of tumor stage Ta-T1 was 212 and T2-T4 was 90.Sixteen patients have lymph node metastasis.Histological low grade was diagnosed in 175 and histological high grade was diagnosed in 127.According to the differences between anatomic structure and cellular composition,bladder tumor tissues can be classified to two localization patterns:(1) intratumoral regions,defined as tumor cell nests;(2) stromal regions,defined as stromal areas that lack direct contact with tumor cells.Therefore,we divided 302 bladder cancer patients into two groups based on the median frequency of intratumoral CD8+ T cells (median,3/× 400 high resolution) and stromal CD8+ T cells (median,37/× 400 high resolution),respectively.x2 analysis was used to evaluated the correlation between CD8+ T cell density and clinicalpathological variables.Kaplan-Meier analysis and Cox proportional hazards regression models were applied to estimate overall survival (OS).Results CD8+ T cells were predominantly located in the intratumoral regions (mean,14 ± 2/× 400 high resolution) rather than in associated stromal regions (mean,50 ± 3/× 400 high resolution,P ＜ 0.05).The density of intratumoral CD8+ T cells was inversely associated with age (P =0.026),tumor size (P ＜ 0.05) and tumor stage (P ＜ 0.05),and could represent a favorable prognostic predictor of OS (HR =0.427,P =0.003).However,the density of stromal CD8+ T cells was positively associated with age (P =0.004) and histological grade (P ＜ 0.01),and could represent an adverse prognostic predictor of OS (HR =2.206,P =0.009).Conclusions Our findings suggest that intratumoral/ stromal CD8+ T cells could potentially serve as favorable/ adverse prognostic markers for bladder cancer patients,respectively.