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.

Objective To explore the relation between the level of oxygen pressure and lactate in arterial blood and prognosis of cardiopulmonary resuscitation (CPR).Methods 36 patients with sudden cardiac arrest received CPR were selected.Patients were divided into 3 groups.The 21 patients who 30 minutes of CPR didn't regain heart beats were group A,those 10 who kept blood circulation for over 2 hours but finally died were group B,and the remaining 5 who survived were group C.Control group was made up of 20 people with no disease.In CPR immediately (0h),1h,3h,6h,12h were measured in blood specimens from arterial partial pressure of oxygen and lactate levels were compared among groups of patients dynamic changes of the index.Results The 3 groups A,B,C significantly reduced blood oxygen pressure,blood lactate increased significantly the CPR in the early,and compared with the control group there was significant difference( P ＜ 0.01 ).The group B CPR 3h,6h,and continue until no significant changes in 12h;The group C CPR 3h,6h began to increase blood oxygen pressure and blood lactate levels begin to decline,blood oxygen pressure increased significantly,lower blood lactate to a lower level after 12h.Taken with marked changes in B group,the difference was significant ( P ＜ 0.05 ).Conclusion Arterial partial pressure of oxygen and blood lactate levels could be used as indicators of prognosis of patients with CPR.Sustained increase in arterial oxygen partial pressure showed a good prognosis,lactate levels continued to rise that a poor prognosis.

Objective To analyze the concentration of epithelial cell derived neutrophil-activating protein 78(CXCL-5) in the sy-(novial) fluid(SF) and peripheral blood in children with rheumatoid arthritis(RA) and evaluate its clinical relevance to the disease development.Methods SF and peripheral sera were taken from 26 children with RA and 16 healthy controls,and CXCL-5 was measured by enzyme linked immunosorbent assay(ELISA).CXCL-5 in SF was also measured in RA children after receiving steroid treatment.Results The levels of CXCL-5 was significantly higher than that in the SF of RA children compared with healthy controls(P0.05).Interestingly,CXCL-5 markedly decreased in RA children after steroid treatment(P

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Objective To evaluate the safety and efficacy of direct celiac ganglion irradiation with 125I seeds for pain relief secondary to advanced pancreatic carcinoma (PC).Methods This study enrolled 23 consecutive patients who had moderate to severe pain resulting from advanced PC.All patients underwent EUS-guided direct celiac ganglion irradiation with 125I seeds.Follow-up was conducted at least once weekly until death.Blood parameters,Visual Analog Scale (VAS) score,mean analgesic consumption,and complications were evaluated during follow-up.Results All patients successfully underwent implantation at one attempt.The mean number of seeds implanted in the celiac ganglion per patient was 4 (range 2-6).Immediately after the procedure,pain relief and analgesic consumption showed no significant changes compared with preoperative values.Six patients (26％) reported pain exacerbation.Two weeks later,the VAS score and mean analgesic consumption were significantly less than preoperative values.No procedure-related deaths or major complications occurred.Conclusion EUS-guided direct celiac ganglion irradiation with 125I seeds can reduce the VAS score and analgesic drug consumption in patients with unresectable PC.

Genetic mutations are important molecular biomarkers for cancer diagnosis and surveillance.Therefore,the development of methods for mutation detection characterized with straightforward,highly specific and sensitive to low-level mutations within various sequence contexts is extremely needed.Although some of the currently available methods have shown very encouraging results,their discrimination efficiency is still very low.Herein,we demonstrate a fluorescent probe coupled with blocker and property of melting temperature discrimination,which is able to identify the presence of known or unknown single-base variations at abundances down to 0.1％ within 20 min.The discrimination factors between the perfect-match target and single-base mismatched target are determined to be 10.15-38.48.The method is sequence independent,which assures a wide range of application.The new method would be an ideal choice for high-throughput in vitro diagnosis and precise clinical treatment.

Pneumoconiosis is the most common occupational disease in China, which severely endangers people's health. Depending on the inhaled air pollutants, pneumoconiosis is classified as anthracosis, silicosis, asbestosis, etc., among which silicosis is the most common and serious. Silicosis is a systemic, poor prognostic disease characterized by diffuse fibrosis of lung tissue, which is caused by long-term exposure to dust with high levels of free silicon dioxide (SiO₂) in the occupational environment. Appropriate treatment in time is important for the disease. Unfortunately, no effective drugs have been approved to delay or even reverse pulmonary fibrosis caused by SiO₂. This review briefly classifies potent therapeutic drugs and compounds in term of mechanisms, providing the probability for clinical treatment of silicosis.

Objective To investigate the safety and efficiency of 125I radioactive stents for advanced extra-hepatic cholangio-carcinoma.Methods We retrospectively reviewed data of 15 consecutive patients with advanced and un-resectable extra-hepatic cholangiocarcinoma,who were treated by radioactive stents.Postoperative complications,patency time of stents,and survival of the patients were assessed.Results Fifteen patients underwent 32 endoscopic sessions of radioactive stents placement.Successful operations were achieved in all patients,and there were no life-threatening complications including perforation,bleeding or bone marrow depression.The average patency time of radioactive stents was 117 ± 105 days (8-295 days).The actual radiation dose was 56.55 ± 17.42 Gy (7.86-82.48 Gy).The median survival time was 420 days (90-1175 days) and survival of 6 patients exceeded 12 months.Conclusion The 125I radioactive stent is safe and effective for patients with advanced unresectable extra-hepatic cholangio-carcinoma.

Objective To observe the effects of Dahuangfuzi decoction on the intestine barrier functional of acute necrotizing pancreatitis in rats. Methods The 60 rats were randomly divided into sham operation group ( n = 19 ), ANP group ( n = 21 ), and Dahuangfuzi treatment group ( n = 20). The rats of ANP group were induced by injecting 1 ml/kg of 4% sodium taurocholate into the pancreatiobiliary duct, and jejunal fistula was esablished. The rats of treatment group received Dahuangfuzi decoction (2 ml, repeated at 4 and 8 h)through jejunum distal stoma tube 0. 5 h after ANP induction. The other 2 groups received same amount of normal saline. Blood sample was collected through abdominal aorta, 24 h after ANP induction, and the serum amylase, endotoxin, D-lactate, plasma diamine oxidase (DAO) were detected. Pancreas, small intestine tissue was harvested for pathologic examination, index of intestinal epithelial damage was measured and ultrastructural changes in small intestinal mucosa was observed. Results The expression of serum amylase, endotoxin,D-lactate, DAO in sham operation group was ( 152 ± 32 ) U/L, (6.95 ± 2.10) pg/L, ( 3.96 ± 1.08 ) μg/mland ( 14.26 ± 2.67 ) μg/ml, while the corresponding values were ( 1549 ± 93 ) U/L, (40.48 ± 3.41 ) pg/L,( 12.34 ± 1.23 ) μg/ml and ( 80.28 ± 3.54) μg/ml in ANP group, and they were (655 ± 49 ) U/L, ( 19.55 ±2.50) pg/L, (6.75 ± 1.36 ) μg/mland ( 20.69 ± 7.53 ) μg/ml in treatment group. The values in ANP group were significantly higher than those in sham operation group. The values in treatment group were significantly lower than those in ANP group, but significantly higher than those in sham operation group ( P ＜ 0.05 or P ＜0. 01 ). The thickness and height of intestinal mucosa in ANP group were ( 389.44 ± 29.87 )μm and ( 16.52 ±3.73) μm, which were significantly lower than those in treatment group [(501.95 ± 45.38 )μm, (27.82 ±5.17)] μm, and in sham operation group [( 658.72 ± 57.49 ) μm, ( 35.49 ± 6.43 )μm, Index of intestional epitholial donage in ANP group was 3.72 ± 0.65 which is significently higher than those in theatment (2.12 ±0.37 ) and in sham operation group (0.85 ± 0.24). The intestinal mucosa histological and ultrastructural changes in Dahuangfuzi treatment group were better than those in ANP group. Conclusions Dahuangfuzidecoction can significantly decrease the damage of intestine barrier function in ANP rats.