Carcinoma, Squamous Cell ; genetics ; Cell Division ; Chromosome Deletion ; Humans ; Laryngeal Neoplasms ; genetics ; Telomere ; genetics ; Tumor Cells, Cultured

Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) catalyze the initial and rate limiting step in the catabolism of tryptophan, which is related to tumor immune tolerance and poor prognosis in patients. In this regard, two enzymes have become important therapeutic targets for tumor immunotherapy. So far, nine IDO1 inhibitors and three IDO1/TDO dual inhibitors have entered clinical trials. This review summarizes the research progress of IDO1 inhibitors, TDO inhibitors and IDO1/TDO dual inhibitors from the perspective of medicinal chemistry.

Adult ; Brain Hemorrhage, Traumatic ; diagnosis ; etiology ; Humans ; Male ; Neck Injuries ; complications ; diagnosis ; Vertebral Artery

Objective:To analyze the clinical manifestations and esophageal motility characteristics of patients with gastroesophageal reflux disease (GERD) and extra-esophageal symptoms.Methods:From January 1 to October 30, 2018, at PLA Rocket Force Characteristic Medical Center, 180 hospitalized patients diagnosed with GERD and extra-esophageal symptoms were retrospectively analyzed. The patients were divided into laryngopharyngeal symptom group (65 cases), airway symptom group (58 cases) and mixed symptom group (57 cases). General data, clinical symptoms, gastroscopic manitestations, the results of high-resolution esophageal manometry and 24-hour multichannel intraluminal impedance and pH monitoring of each group were analyzed and compared. Chi-square test and one-way analysis of variance were used for statistical analysis.Results:The patients aged <40, 40 to 60 and >60 years accounted for 12.8% (23/180), 53.3% (96/180) and 33.9% (61/180), respectively, and the difference was statistically significant ( χ2=12.030, P=0.017). There were 18.9%(34/180) of patients without typical reflux symptoms. There were statistically significant differences in the incidence of ectopic esophagogastric mucosa or Barrett esophagus under gastroscopy between laryngopharyngeal symptom group, airway symptom group and mixed symptom group (21.5%, 14/65; 5.2%, 3/58 and 8.8%, 5/57, respectively) ( χ2=8.578, P=0.014). There were no statistically significant differences in the lower esophageal sphincter pressure (LESP), upper esophageal sphincter pressure or distal contractile integral between laryngopharyngeal symptom group, airway symptom group and mixed symptom group ((8.57±0.76), (8.87±0.79), and (10.51±0.97) mmHg (1 mmHg=0.133 kPa); (44.75±2.86), (42.81±4.06), and (39.14±3.20) mmHg; (506.13±64.30), (432.59±78.10), and (682.99±82.28) mmHg·s·cm)(all P>0.05). The DeMeester score of laryngopharyngeal symptom group , mixed symptom group and airway symptom group was (14.33±2.09), (21.94±5.30) and (30.47±5.85) points, respectively, and the difference was statistically significant ( F=3.226, P=0.043). The results of multi-channel impedance monitoring showed that acid reflux and weak acid reflux were the main reflux in the patients, which accounted for 55.5% (76/137) and 34.3% (47/137), respectively. Among 87.6% (120/137) of the patients, reflux mainly occurred in the upright position while 12.4% (17/137) of the patients had reflux in the supine position. Conclusions:The extra-esophageal symptoms of GERD is associated with age. Ectopic esophagogastric mucosa or Barrett esophagus are more common in GERD patients with laryngopharyngeal symptoms. There are more acid exposure and pathologic acid reflux in GERD mainly with airway symptoms. Weak acid reflux at upright position plays an important role in the reflux mechanism of GERD with extra-esophageal symptoms.

98 %).Conclusions Saponins are the major active ingredients in Radix Polygalae.Tenuifolin as an alkaline hydrolysis product of total saponins can be used as a chemical reference substance for the quality control of Radix Polygalae.

Objective　To study the effect of portal vein blocking on the permeability of the intestinal mucosa in pigs. Methods　Healthy Rongchang pigs were divided into 3 groups: ① sham operation group(SO), ② portal vein clamping for 45 min group (PVC-45'), ③ portal vein clamping for 60 min group (PVC-60'). Urine lactulose/mannitol(L/M) ratio was measured after portal vein blocking. Results　The L/M ratio was increased significantly (P<0.05) in PVC-45' and 60' groups than in SO group, with that of PVC-60' higher than that of PVC-45' group, but not significantly. Conclusion　The increase of intestinal mucosal permeability after portal vein blocking is an early and important index for the damage of the intestinal mucosa barrier.

To study the effects of Feiyanning Decoction, a compound traditional Chinese herbal medicine, on the ratio of CD4(+)CD25(+) regulatory T cells and expression of transcription factor Foxp3 in mice with Lewis lung cancer.

Objective To observe the effects of tea polyphenols (TP) on cardiac function and myocardial ultrastructure in rats after repeated +10 Gz stress. Method Twenty four male Wistar rats were randomly divided into three groups (n=8 each): group A (control), group B (+10 Gz), group C (+Gz with TP). Group B and C were repeatedly exposed to +10 Gz (each for 30 s, onset rate about 0.5 G/s, 3 times/d with +1 Gz 1 min intervals, 3 d/wk, 4 weeks in total), but group A was only submitted to +1 Gz. TP(200 mg.kg-1) was given orally to group C about 1h prior to the +Gz experiment, and distilled water was given to group A and B.Function of isolated rat working hearts and myocardial ultrastructure were observed. Result A significant decrease of left ventricular systolic pressure (LVSP) and injury of myocardial structure in rats were demonstrated after repeated +10 Gz stress. But TP could remarkably elevate the LVSP and improve myocardial ultrastructural injury in +10Gz stressed rats. Conclusion These results indicated that repeated high G exposure may produce cardiac structural and functional injuries in rats which might be partly related to free radical metabolism; and antioxidant TP had significant protective effects on the hearts of +Gz stressed rats.

To study the effect of Feiyanning Decoction (FYN), a compound traditional Chinese medicine, on expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) activated by tumor necrosis factor-α (TNF-α) in human lung adenocarcinoma epithelial cell line (A549).