ABSTRACT
Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H2O2), which is then used in the Cu+-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.
ABSTRACT
OBJECTIVE： To systematically evaluate the effectiveness and safety of Xingpi yang’er granules（XYG） combined with Clostridium butyricum live powder （CBLP） in the treatment of pediatric dyspeptic diarrhea， and provide evidence-based reference for clinical medication. METHODS： Retrieved from Cochrane Library， PubMed， Embase， CBM， CNKI， VIP and Wanfang database， randomized controlled trials （RCTs） about XYG combined with CBLP（trial group）vs. CBLP alone（control group）in the treatment of pediatric dyspeptic diarrhea were collected. After literature screening， data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0 bias risk evaluation tool， Meta-analysis was performed by using Rev Man 5.3 software. TSA 0.9 software was used for trail sequential analysis. RESULTS： A total of 8 RCTs with 857 participants were included. Total response rate of trial group [RR＝1.20，95％CI（1.13，1.28），P＜0.000 01] was significantly higher than that of control group. Abdominal pain relief time [MD＝－1.18，95％CI（－1.42，－0.94），P＜0.000 01]， abdominal distension relief time [MD＝－1.32， 95％CI（－1.94，－0.70），P＜0.000 1]， diarrhea relief time [MD＝－2.07， 95％CI（－2.38，－1.76），P＜0.000 01]， the time of stool traits returned to normal[MD＝－2.16，95％CI（－2.43，－1.88）， P＜0.000 01] in trial group were significantly shorter than control group. The stool frequency [MD＝－1.72，95％CI（－2.18，－1.24）， P＜0.000 01] in trial group were significantly less than control group. The incidence of ADR in trial group was significantly lower than control group （P＜0.05）， or there was no statistical significance in the incidence of ADR between 2 groups （P＞0.05）， or no significant ADR was founded in 2 groups. Trial sequential analysis showed that the evidence of total response rate of XYG combined with CBLP in the treatment of pediatric dyspeptic diarrhea was accurate. CONCLUSIONS： XYG combined with CBLP is effective and safe for pediatric dyspeptic diarrhea.
ABSTRACT
OBJECTIVE:To provide reference for improving the level of pediatric drug supply and guarantee. METHODS:Questionnaire survey about the situation and causes of pediatric drug shortage was conducted in 13 third-level hospitals of Jiangsu province [directors of pharmacy department(or drug purchasers)and clinical pharmacists of each surveyed hospital]. The survey da-ta were analyzed statistically so as to provide suggestions. RESULTS:A total of 26 questionnaires were distributed,and 26 effec-tive questionnaires were collected with effective recovery rate of 100%. In 13 hospitals,special drugs for children were mostly less than 5% of hospital drug list. There were 82 kinds of special drugs for children(containing hospital preparation),mainly including Chinese patent medicine(35.37%),drugs for respiratory system(12.20%),vitamin,mineral substance and enteral and parenteral nutrient solution(10.98%). The most types of anti-infective drugs,antineoplastics,nervous system drugs and psychotropic drugs, digestive system drugs were in shortage among 126 pediatric drugs in shortage(8.73%). The reasons for pediatric drug shortage mainly included price(38.10%),production break(32.54%),failure to bid or no supply(13.49%). The shortage of cheap drugs with price of 0.01-10.00 was the most serious,accounting for 57.94% of the varieties in shortage supply. Respondents thought that special drug shortage most affected clinical treatment(38.46%),followed by poisoning rescue drugs(30.77%)and orphan drugs(15.38%). CONCLUSIONS:Special drugs for children account for a very small proportion in the hospital drugs list. Pediatric drug shortage is affected by many factors. Cheap drug shortage is the most serious. The shortage of special drugs for children and poison-ing rescue drugs is considered to have a great impact on clinical treatment. It is suggested to establish special drugs for children pro-tective policy,improve drug circulation,promote pediatric drug clinical trial and intensify the research and development of special drugs for children so as to guarantee pediatric drug supply.
ABSTRACT
Abnormal aggregation of α-synuclein(α-Syn) is thought to be a key event in the pathogenesis of Parkinson disease (PD). In recent years, it was shown that above 90% of α-Syn deposited in Lewy bodies in brain tissues from patients with PD is phosphorylated, which suggested that α-Syn phosphorylation be connected with the occurrence of PD. Several kinds of phosphokinases can make α-Syn phosphorylated, however the precise roles of these phosphokinases in PD are less clear.