Objective An interaction network among PD-1-ligands and other proteins were built to add deeper understanding of PD-1 signal pathway and to supply the theoretical data on the clinical application study of PD-1 and its ligands.Methods Searching the literature about PD-1 and its ligands in the PubMed,the result of which would be used to summarize the proteins that had been reported to have interactions with PD-1 and its ligands,and then,quadratic search would be performed on these proteins.Finally,the software Cytoscape would be used to build and analyze the interaction network and verified by PCR.Results There were 122 and 126 nodes in the PD-1/PD-L1 network and PD-1/PD-L2 network respectively.These proteins were involved in TCR signal path-way,cell adhesion,JAK-STAT signal pathway and interaction between cytokines.Meanwhile,a perspective that PD-L1 may influ-ence on CXCR4 through JAK-STAT pathway based on the network which had been supported by qPCR.Conclusion The bioinfor-matics suggested that there are differences between the mechanism of PD-1/PD-L1 and PD-1/PD-L2.Additionally,the method, which was based on the literature mining and bioinformatics,is good to put the biological literature to rational utilization and to pro-vide guidance for experiments.

Background: Perineural dexamethasone has been regarded as a promising adjunct for prolonging the duration of nerve blocks. However, it is uncertain whether its effects are due to local effects on the nerves or from systemic absorption. This systematic review aimed to compare the duration of postoperative analgesia associated with perineural versus intravenous dexamethasone as an adjunct to peripheral nerve blocks. Methods: A total of 2,216 relevant academic articles were identified after a comprehensive search of PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from 1967 until 2020. All randomized controlled trials that compared perineural and intravenous dexamethasone as adjuncts to peripheral nerve limb blocks were included. Results: Fifteen randomized controlled trials (1,467 cases; 738 perineural dexamethasone, 729 intravenous dexamethasone) were eligible. The primary outcome (duration of analgesia) was significantly longer in the perineural than in the intravenous dexamethasone group (mean difference [MD]: 2.72 h, 95% CI [1.42, 4.01], P < 0.001). Perineural dexamethasone was also found to prolong the sensory block (MD: 3.45 h, 95% CI [1.36, 5.54], P = 0.001) and lower 24 h postoperative pain scores (MD: −0.74 h, 95% CI [−1.40, −0.07], P = 0.03). Conclusions This review confirms the greater efficacy of perineural compared to intravenous dexamethasone in prolonging the analgesic duration of peripheral nerve blocks. However, the extent of prolongation was small and may not represent a clinically meaningful difference.

Objective To investigate the effects of different doses of pituitary adenylate cyclase- activating polypeptide(PACAP)on the functional and morphological outcome in a mice model of Parkinson' s disease(PD)rendered by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Methods Male mice were treated with PACAP 0.02, 0.20 or 2.00 ?g by iv bolus for 7 days after MPTP was administered, and were compared with the saline-treated mice.The immunohistochemistry and Western blot were used to detect the alterations of PD biomarker including tyrosine hydroxylase(TH), dopamine transporter(DAT)and vesicular monoamine transporter2(VAMT2).In addition, monoamine neurotransmitters in the striatum of mice were measured by the high performance liquid chromatography (HPLC).Results TH immunohistochemistry indicated that the number of TH-positive neurons in the substantia nigra was increased in all PACAP-treated mice(PACAP(0.02 ?g/d)group was 93.33?4.87, F=85.85,P

Solid dispersions (SD) as a preparation of intermediates have played an important role in improving the dissolution of insoluble drugs and its bioavailability.SD technique is one of the most promising techniques to improve the dissolution and solubility of insoluble drugs,and the development of SD technique will promote the gradual perfection in preparative field.This review focuses on the carrier materials of SD,various new preparation techniques and their comparisons,application of solid dispersion formulations,and stability problems of SD.The factors influencing the stability of SD are described,and the effective measures to prevent the aging of SD are put forward.Finally,the review puts forward the practical suggestions of the solid dispersion technique.

OBJECTIVETo observe the development of arrhythmia induced by ischemia/reperfusion (I/R) of the right coronary artery in rabbits and the intervening effect of Chinese medicine Qiangxin Fumai Granule (QFG), a Chinese preparation for activating yang and promoting blood circulation, on it.

METHODSRabbit right coronary artery I/R model was adopted. Forty healthy adult rabbits were randomly divided into 5 groups, the sham-operation group, the model group, the atropine group, the high-dose QFG group, and the low-dose QFG group, eight in each group. The drugs were administered via duodenal perfusion 10 min after ischemia. The changes of AA interval before and after medication were observed and the scores of arrhythmia were calculated.

RESULTSDuring ischemia period, AA interval prolonged for more than 40 ms in the model group, and the scores of arrhythmia showed a rising trend along with the prolonging of ischemia, with the presence of atrial-ventricular block (AVB) and aggravating of sinus and atrial arrhythmia; during reperfusion period, the incidence of AVB decreased, and AA interval somewhat decreased. The AA intervals and scores of arrhythmia in the high and low-dose QFG groups were significantly lower than those in the model group respectively (P < 0.01 or P < 0.05).

CONCLUSIONQFG is beneficial for shortening AA interval and preventing arrhythmia induced by I/R.

Animals ; Anti-Arrhythmia Agents ; administration & dosage ; pharmacology ; therapeutic use ; Arrhythmias, Cardiac ; drug therapy ; physiopathology ; Coronary Artery Disease ; complications ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Female ; Male ; Myocardial Ischemia ; complications ; Myocardial Reperfusion Injury ; etiology ; physiopathology ; Phytotherapy ; Rabbits ; Random Allocation ; Treatment Outcome

OBJECTIVETo evaluate the prognostic value of expression of fatty acid synthase (FASE), HER-2/neu, bcl-2 and p53 in stage I non-small cell lung cancer (NSCLC).

METHODSExpression of FASE, HER-2/neu, bcl-2 and p53 protein was detected by immunohistochemical staining in 84 patients with stage I NSCLC who underwent surgery. Multiple clinical parameters and survival were analyzed.

RESULTSThe expression of FASE, HER-2/neu, bcl-2 and p53 was 29.8%, 40.5%, 33.3% and 39.3%, respectively. The local recurrence and bone-metastasis rate were higher in FASE positive patients than in negative patients (28.0% vs 10.2%, P = 0.05; 61.5% vs 23.9%, P = 0.017, respectively). The 5-year survival rate was lower in HER-2/neu and FASE positive patients than in negative patients (37.7% vs 67.7%, P = 0.0083; 35.1% vs 66.1%, P = 0.0079, respectively), which showed that HER-2/neu and FASE expression were associated with significantly poor survival. Patients whose tumors were both HER-2/neu and FASE negative had better outcome, with a 5-year survival rate of 78.2%, compared with 36.3% in those whose tumors were positive for either one (P = 0.002). However, bcl-2 and p53 were not independent prognostic factors for survival.

CONCLUSIONHER-2/neu and FASE are independent prognostic factor in stage I non-small cell lung cancer patients who expressed one or both markers.

Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Bone Neoplasms ; secondary ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; secondary ; surgery ; Fatty Acid Synthases ; metabolism ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; metabolism ; mortality ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Receptor, ErbB-2 ; metabolism ; Smoking ; adverse effects ; Survival Rate ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo study the effect of the Chinese medicine Qiangxin Fumai Granule (, QFG) on electrophysiological functions of the sinoatrial node during ischemia-reperfusion (IR) of the right coronary artery in rabbits.

METHODSThe right coronary artery IR model in rabbits was adopted. The modeled rabbits were randomly divided into 4 groups: the model group, the atropine group, the high-dose QFG group, and the low-dose QFG group, with 8 animals in each group. In addition, twelve rabbits were selected for the sham-operative group. The drugs were administered once via duodenal perfusion after modeling had been stabilized for 10 min. The changes in AA interval, the sinoatrial conduction time (SACT), the sinus node recovery time (SNRT), the corrected sinus node recovery time (CSNRT) and the index of sinus node recovery time (ISNRT) at different time points during ischemia and reperfusion were measured.

RESULTSThe AA interval was prolonged for more than 40 ms in the model group during ischemia. Compared with the model group, the four electrophysiological parameters abovementioned in the high-dose QFG group and the low-dose QFG group were decreased to different extents at each time point (P<0.01 or P<0.05), and no statistically significant differences were found between the QFG groups and the atropine group (P>0.05).

CONCLUSIONQFG is beneficial for accelerating the recovery of sinus node autorhythmicity and conduction function, so as to protect electrophysiological functions of the sinoatrial node. Accelerating the recovery of autorhythmicity and conduction function in the sinus node is considered its electrophysiological mechanism in the treatment of sinoatrial node injury induced by ischemia.

Animals ; Coronary Vessels ; drug effects ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Electrophysiological Phenomena ; drug effects ; Heart Conduction System ; drug effects ; Myocardial Reperfusion Injury ; drug therapy ; physiopathology ; Phytotherapy ; Rabbits ; Sinoatrial Node ; drug effects ; physiopathology ; Time Factors

OBJECTIVETo analyze several methods of wound repair for deep partial thickness burn wounds retrospectively, so as to evaluate the significance of improvement of wound microcirculation on wound healing.

METHODS(1) 2,976 burn patients admitted to our department were enrolled in the study, among them 614 undertook tangential excision, 32, eschar abrasion, 86 allo-skin coverage after debridement, 1836 tropical application of silver sulfadiazine and 408 with traditional Chinese medicine (Jing Wan Hong ointment) with gauze bandage. The results of the management with different methods were compared. (2) Rat model with deep partial thickness burn was reproduced and topical application of silver sulfadiazine was given. The rats were randomly divided into control (n = 10, with normal saline injected via caudal vein within 5 minutes postburn), and treatment (n = 10, with batroxobin injected via caudal vein within 5 minutes postburn) groups. The blood flow perfusion unit in the wound skin was measured before burn and at 0.5 to 72 postburn hours by Laser Doppler. The wound healing rate, contraction rate and wound healing time in each group were calculated on 14 and 18 postburn days (PBDs). The number of hair follicles after wound healing was observed by histological method.

RESULTS(1) The burn wound treated by tangential excision healed within 2 to 3 post operation weeks (POWs), with the healing rate of 94.8% in patients with burn covering 50% - 70% TBSA and 93.4% in those with burn of 80% approximately 98% TBSA. The healing time of patients with allo-grafts coverage after eschar abrasion was 13.8 +/- 2.1 days without scar formation. The wound healing time was 18.0 +/- 2.3 day in 82 patients with allo-graft coverage after debridement, and it was 26.0 +/- 3.2 days with subeschar healing in 1658 patients with topical application of silver sulfadiazine. Infection in burn wound was encountered in most patients undergoing traditional Chinese medicine bandage treatment with wound healing time of 26.0 +/- 2.8 days in the lower extremities. (2) The blood flow perfusion unit of the rats in the treatment group was significantly higher than that in the control group (P < 0.01). The wound healing rate in treatment group on 14 and 18 PBD was obviously higher than that in the control group (P < 0.01). But the wound contraction rate in the two groups was similar (P > 0.05). The wound healing time in treatment group was much shorter than that in control group (P < 0.01). A few hair follicles remained in the dermis of the rats in the control group on 30 PBD, and the number was evidently smaller than that in the treatment group (P < 0.01).

CONCLUSIONEarly tangential excision and eschar abrasion remained better methods in the management of deep partial thickness burn wounds, as they could ameliorate burn wound infection, shorten treatment period, raise wound healing rate and quality. Application of batroxobin could accelerate wound healing rate by improving wound microcirculation in deep partial thickness burn wound.

Adult ; Animals ; Batroxobin ; therapeutic use ; Burns ; pathology ; surgery ; therapy ; Female ; Humans ; Male ; Microcirculation ; Rats ; Rats, Wistar ; Retrospective Studies ; Skin ; blood supply ; Skin Transplantation ; methods ; Wound Healing

OBJECTIVETo detect the KChIP2 mRNA level in rheumatic heart disease patients with or without atrial fibrillation (AF) by real-time PCR.

METHODSRight atrial appendage samples from rheumatic heart disease patients with (n = 17) or without AF (n = 13) were obtained during cardiac surgery. Total RNA was extracted from the atrial tissues, and the KChIP2 and Kv4.3 mRNA were detected by SYBR Green I real-time PCR with the GAPDH as the house keeping gene.

RESULTThe ratio of KChIP2/GAPDH (0.1468 +/- 0.0452 vs. 0.2200 +/- 0.0388, P<0.01) and the ratio of Kv4.3/GAPDH (0.3946 +/- 0.1826 vs. 0.5257 +/- 0.1427, P<0.05) were significantly lower in AF patients compared to non-AF patients.

CONCLUSIONDown-regulated atrial KChIP2 and Kv4.3 mRNA expressions in rheumatic heart disease patients with chronic AF might be one of the molecular bases responsible for the down-regulation of the I(to) current density of AF.

Adult ; Atrial Fibrillation ; genetics ; Down-Regulation ; Female ; Humans ; Kv Channel-Interacting Proteins ; genetics ; Male ; Middle Aged ; Myocytes, Cardiac ; metabolism ; RNA, Messenger ; genetics ; Rheumatic Heart Disease ; genetics ; Shal Potassium Channels ; genetics

OBJECTIVEIt has been proposed that genetic polymorphisms in apoptosis-related genes might be associated with sensitivity of cancer cells to platinum-based chemotherapy. This study examined the relationship between p53 and p73 genetic polymorphisms and the response to platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).

METHODSA total of 165 patients with advanced NSCLC treated with platinum-based chemotherapy were genotyped for the p53 codon 72 Pro-->Arg and p73 exon 2 G4C14-->A4T14 polymorphisms using PCR-RFLP and ARMS-PCR assays. Clinical response to the chemotherapy was obtained after 2 to 3 cycles. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model. All statistical tests were two-sided.

RESULTSThe p53 Pro allele carriers had higher response rate than non-carriers (OR = 2.46; 95% CI = 1.11 - 5.45). A higher response rate was also observed for the p73 G4C14/A4T14 or A4T14/A4T14 genotype, compared with the G4C14/G4C14 genotype (OR = 2.22; 95% CI = 1.14 - 4.30). When these two polymorphisms were combined to be analyzed, it was found that the response rate in those carrying the wild-type genotypes at both genes was only 7.7%, whereas the response rates in patients carrying 1, 2, or more than 2 variant alleles of p53 and p73 were 34.8%, 42.2% and 40.7%, respectively.

CONCLUSIONThose results suggest that p53 and p73 polymorphisms may be associated with clinical responsiveness to platinum-based chemotherapy in advanced NSCLC.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; pathology ; Cisplatin ; administration & dosage ; DNA-Binding Proteins ; genetics ; Exons ; Female ; Genotype ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Nuclear Proteins ; genetics ; Paclitaxel ; administration & dosage ; Polymorphism, Genetic ; Tumor Protein p73 ; Tumor Suppressor Protein p53 ; genetics ; Tumor Suppressor Proteins ; genetics