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.

[摘 要] 目的：设计和构建表达PD-1 shRNA的靶向CD19 CAR-T细胞并验证其体外肿瘤细胞杀伤能力。方法：设计并构建表达PD-1 shRNA的CD19 CAR分子基因，将其包装成逆转录病毒载体，通过qPCR法检测病毒载体拷贝数。将慢病毒转导人原代T细胞，获得三种CAR-T细胞，分别为RNAU6-CD19 CAR-T、PD-1 shRNA1-CD19 CAR-T、PD-1 shRNA2-CD19 CAR-T细胞。采用qPCR法检测三种CAR-T细胞中PD-1 mRNA的表达水平，流式细胞术检测三种CAR-T细胞中PD-1表达水平，萤光素酶报告基因实验、流式细胞术检测在不同效靶比时CAR-T细胞对CD19阳性靶细胞（人淋巴瘤daudi细胞）的杀伤功能。结果：RNAU6-CD19 CAR、PD-1 shRNA1-CD19 CAR、PD-1 shRNA2-CD19 CAR三种CAR分子成功包装成逆转录病毒载体，病毒载体拷贝数均高于1×107拷贝/mL，转导人原代T细胞获得CAR-T细胞，RNAU6-CD19 CAR-T、PD-1 shRNA1-CD19 CAR-T、PD-1 shRNA2-CD19 CAR-T细胞转导效率分别为43.1%、55.1%、41.7%。与RNAU6-CD19 CAR-T细胞相比，PD-1 shRNA1-CD19 CAR-T、PD-1 shRNA2-CD19 CAR-T细胞中PD-1 mRNA表达水平均显著降低（均P<0.01）、细胞表面PD-1表达水平更低（均P<0.01）、体外对daudi细胞的杀伤率更高（P<0.05或P<0.01）。结论：成功构建表达PD-1 shRNA的靶向CD19 CAR-T细胞，其对CD19阳性靶细胞的杀伤率显著提高，PD-1 mRNA及其翻译产物PD-1的表达减少，CAR-T细胞的耗竭减缓。

ObjectiveTo screen and establish animal models of combined stasis and toxin syndrome based on the comparison of three modeling methods， i.e.， carrageenan （Ca）， Ca combined with dried yeast （Ca+Yeast）， and Ca combined with lipopolysaccharide （Ca+LPS）. MethodForty SPF male SD rats were randomly divided into normal group， Ca group， Ca+Yeast group， and Ca+LPS group， with 10 rats in each group. The Ca group， Ca+Yeast group， and Ca+LPS group received an intraperitoneal injection of Ca （10 mg·kg^-1） on the first day. The Ca+LPS group received an intraperitoneal injection of LPS （50 μg·kg^-1） on the second day， and the Ca+Yeast group received a subcutaneous injection of dry yeast suspension （2 mg·kg^-1） on the back on the second day. The rectal temperature of each group was dynamically observed after modeling. After 24 hours of modeling， the macroscopic evaluation indexes， including tongue manifestation， pulse， and black tail length in each group were observed. The PeriCam PSI imaging system was used to detect the blood flow perfusion of the rat tail. The automatic hemorheology analyzer was used to measure the whole blood viscosity and plasma viscosity of each group. The PL platelet function analyzer was used to detect the platelet aggregation rate of the rats. The enzyme-linked immunosorbent assay （ELISA） was used to detect the interleukin-6 （IL-6） level in the rat plasma. The myocardial tissue， brain tissue， and lung tissue of each group of rats were observed by hematoxylin-eosin （HE） staining. ResultCompared with the normal group， all three model groups showed varying degrees of black tail （P<0.05， P<0.01）， reduced blood flow perfusion at the tail end （P<0.05， P<0.01）， decreased R， G， and B values of tongue manifestation （P<0.05， P<0.01）， and increased maximum platelet aggregation rate （P<0.05， P<0.01）. The pulse amplitudes of the Ca+Yeast group and the Ca+LPS group were lower than that of the normal group （P<0.05， P<0.01）. In addition， the average rectal temperature of the Ca+Yeast group increased after 24 hours of modeling （P<0.01）， and the low-， medium-， and high-shear whole blood viscosity and plasma viscosity increased （P<0.05， P<0.01） as compared with those in the normal group. Additionally， the expression level of the plasma inflammatory factor IL-6 was significantly up-regulated （P<0.05）. Pathological morphology results showed that the Ca+Yeast group had the most severe pathological changes， with small foci of myocardial fiber dissolution， inflammatory cell infiltration， and fibroblast proliferation observed. In the hippocampal area， the neurons were sparse and had undergone red degeneration. In the small focus of the lung interstitium， lymphocytes and neutrophils were infiltrated. ConclusionThe animal model of combined stasis and toxin syndrome was properly established using Ca+Yeast. The systematic evaluation system of the model， which includes traditional Chinese medicine four diagnostic information， western medicine microscopic indicators， and tissue pathological morphology， is worthy of consideration and reference by researchers.

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 investigate the effects and underlying mechanism of Yinxing Mihuan oral solution （YM） on neovascularization and vascular remodeling in chemical photothrombosis-induced focal cerebral ischemia model in mice. MethodFifty SPF C57BL/6J mice were randomly divided into sham group， model group， ginaton group （12.5 mg·kg^-1）， and low- （YM-L， 412 mg·kg^-1） and high-dose （YM-H， 824 mg·kg^-1） YM groups， with 10 mice in each group. The focal cerebral ischemia model was established by chemical photothrombosis method. Drugs in each group were administered by gavage for 14 consecutive days after operation. The modified neurological severity score （mNSS） and measurement of forelimb grasping were used to evaluate the neurologic impairment of mice. The vascular density of infarct border-zone （IBZ） was measured by fluorescein labelled dextran （FITC-dextran） method. The morphology of IBZ was evaluated and observed by hematoxylin-eosin （HE） staining. The expression of proteins related to neovascularization and vascular remodeling in brain tissues， including vascular endothelial growth factor （VEGF）， platelet and endothelial cell adhesion molecule 1 （CD31）， hypoxia-inducible factor-1α （HIF-1α）， von Willebrand factor （vWF）， and angiogenin （ANG）， was detected by Western blot. ResultCompared with the sham group， the model group showed manifest neurological deficits （P<0.01）， weakened forelimb grasping （P<0.01）， increased vascular density of IBZ （P<0.01）， and obvious pathological changes， such as neuronal necrosis and gliocyte proliferation. After treatment for 14 days， compared with the model group， the YM-H group showed improved neurological deficits （P<0.01）， and the YM-L group and the YM-H group showed strengthened forelimb grasping （P<0.01）. Moreover， the YM-L group displayed increased vascular density of IBZ （P<0.05）， reduced pathological damage， and up-regulated protein expression of CD31， ANG， HIF-1α， and vWF （P<0.05， P<0.01）. ConclusionYM could improve motor function and pathological morphological impairment in chemical photothrombosis-induced focal cerebral ischemia mouse model， and the underlying mechanism might be related to the promotion of neovascularization and vascular remodeling in IBZ.

Traumatic spinal cord injury (TSCI) is a common nerve injury in the world, which has a high incidence and disability rate. Intraspinal pressure (ISP) monitoring is performed by placing a pressure sensing probe under the dura of the most severe part of the spinal cord injury after anterior/posterior laminectomy or vertebral body decompression. ISP value is monitored dynamically and objectively in real time by the pressure sensing system. Recent studies have found that ISP monitoring plays an important role in the clinical management and prognosis evaluation of TSCI. The author reviews the recent advance in ISP monitoring in TSCI in order to provide references for the improvement of clinical diagnosis and treatment of TSCI.

Traumatic spinal cord injury (TSCI) is a common nerve injury in the world, which has a high incidence and disability rate. Intraspinal pressure (ISP) monitoring is performed by placing a pressure sensing probe under the dura of the most severe part of the spinal cord injury after anterior/posterior laminectomy or vertebral body decompression. ISP value is monitored dynamically and objectively in real time by the pressure sensing system. Recent studies have found that ISP monitoring plays an important role in the clinical management and prognosis evaluation of TSCI. The author reviews the recent advance in ISP monitoring in TSCI in order to provide references for the improvement of clinical diagnosis and treatment of TSCI.

Objective:To investigate the efficacy and safety of nano-particle albumin bound paclitaxel in the treatment of patients with advanced and relapsed cervical cancer.Methods:A retrospective cohort study was conducted. Among the cervical cancer patients who were diagnosed and treated in Affiliated Hospital of Yan'an University from January 2013 to January 2018, 52 advanced and relapsed cases were selected as the research objects. The chemotherapy protocol of nano-particle albumin bound paclitaxel and cisplatin was used, and the efficacy and toxicity of chemotherapy were analyzed.Results:The total objective remission rate of 52 patients with advanced or relapsed cervical cancer was 67.3% (35/52), the disease control rate was 88.5% (46/52), and the progression-free survival time was (11.7±3.6) months. The objective remission rate in patients who had received radiotherapy and with a time interval of > 12 months since their last chemotherapy was higher than that in patients who had not received radiotherapy and with a time interval of ≤ 12 months since their last chemotherapy [76.9% (30/39) vs. 46.2% (6/13), χ2 = 4.333, P = 0.037; 78.9% (15/19) vs. 43.8% (7/16), χ2 = 4.609, P = 0.032]. Late stage, relapse, whether received radiotherapy, whether received chemotherapy and the time from the previous chemotherapy had no effect on the disease control rate (all P > 0.05). The progression-free survival time in patients who underwent radiotherapy and with a time interval of > 12 months since their last chemotherapy was longer than that in patients who had not received radiotherapy and with a time interval of ≤12 months since their last chemotherapy [(13.0±4.4) months vs.(8.7±2.9) months, t = 3.029, P = 0.004; (12.8±3.1) months vs. (9.6±4.0) months, t = 2.665, P = 0.012]. The highest incidence rates of adverse reactions were myelosuppression (82.7%, 43/52) and gastrointestinal reaction (65.4%, 34/52), and the most common grade Ⅲ-Ⅳ adverse reaction was myelosuppression (20 cases). Conclusion:The efficacy and safety of nano-particle albumin bound paclitaxel combined with cisplatin in the treatment of advanced and relapsed cervical cancer are reliable.

Homoeostasis depends on the close connection and intimate molecular exchange between extracellular, intracellular and intercellular networks. Intercellular communication is largely mediated by gap junctions (GJs), a type of specialized membrane contact composed of variable number of channels that enable direct communication between cells by allowing small molecules to pass directly into the cytoplasm of neighbouring cells. Although considerable evidence indicates that gap junctions contribute to the functions of many organs, such as the bone, intestine, kidney, heart, brain and nerve, less is known about their role in oral development and disease. In this review, the current progress in understanding the background of connexins and the functions of gap junctions in oral development and diseases is discussed. The homoeostasis of tooth and periodontal tissues, normal tooth and maxillofacial development, saliva secretion and the integrity of the oral mucosa depend on the proper function of gap junctions. Knowledge of this pattern of cell-cell communication is required for a better understanding of oral diseases. With the ever-increasing understanding of connexins in oral diseases, therapeutic strategies could be developed to target these membrane channels in various oral diseases and maxillofacial dysplasia.
Bone and Bones ; Cell Communication ; Connexins ; metabolism ; physiology ; Gap Junctions ; metabolism ; pathology ; Homeostasis ; physiology ; Humans ; Mouth Diseases ; Phosphorylation