Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.

ObjectiveTo review the efficacy and safety in secondary prevention of ischemic stroke with cilostazol or aspirin.Methodswe searched Cochrane Library(the 4th issue, 2009 ), PubMed(1980.1～2009.11), EMBASE(1980.1～2009.11), CBM(1978.1～2009.11), CNKI(1979.1～2009.11) and some other databases, then collected all of the studies describing the outcomes in curing the ischemic stroke after taking cilostazol or aspirin. According to the strict inclusion and exclusion criteria, two reviewers independently selected trials, extracted datas, made cross-checking and methodological quality assessment of the homogeneity studies by using the Cochrane systematic review methods, then made Meta analysis using RevMan 5.0 software.ResultsThis systematic review study included two randomized controlled trials and a cross-over trial, which contained a total of 838 participants. The evidence quality of one of the randomized controlled trials was high, however, the evidence quality of another randomized controlled trial and the cross-over trial was poor. Meta analysis results suggested that the effectiveness of cilostazol and aspirin in the secondary prevention of ischemic stroke performed no significantly statistical difference: primary endpoint(30 d［RR=3.00, 95%CI(0.31,28.70)］; 90 d［RR=1.67, 95%CI(0.40,6.92)］; 180 d［RR=1.25, 95%CI(0.50, 3.13)］; 360 d［RR=0.65, 95%CI(0.33, 1.29)］; 540 d［RR=0.80,95%CI(0.54, 1.18)］); combined endpoint(30 d［RR=4.00, 95%CI(0.45,35.61)］; 90 d ［RR=1.75,95%CI(0.52,5.93)］; 180 d［RR=1.00, 95%CI(0.48, 2.07)］; 360 d ［RR=0.77, 95%CI(0.45, 1.29)］; 540 d［RR=0.66,95%CI(0.40,1.09)］); the recurrence of ischemic stroke: cilostazol group: RR=0.64, 95%CI(0.31,1.30)，aspirin group: RR=0.21, 95%CI(0.04,1.06); PDMP［RR=1.00, 95%CI(0.39, 2.58)］. But in terms of the probability of intracranial hemorrhage (［RR=7.14, 95%CI(0.7,58.33)］) and other safety standards, taking cilostazol performed lower than taking aspirin.ConclusionThe side effects of cilostazol and aspirin in the treatment for ischemic stroke were similar to each other, but in terms of the probability of dizziness, headache, tachycardia and palpitation, taking cilostazol performed higher than taking aspirin, however, taking cilostazol performed lower in the probability of intracranial hemorrhage and other organ hemorrhage than taking aspirin. Since this study included a small amount of studies, in which the evidence quality of one of the randomized controlled trials and the cross-over study was poor, therefore, it would be necessary to make a further validation with lots of high-quality clinical trials.

Cell therapy refers to a method that transplants stem cells or differentiated functioning cells into diseased regions to compensate the losing functions of diseased cells or uses the stem cells for treatment of diseases after in vitro genetic manipulation. After more than 30 years of study, great progress in hepatocyte transplantation technique has been acquired. This technique can acquire in situ liver transplantation effects. Hepatocyte transplantation, as an effective method for treatment of fulminant hepatic failure, has been widely confirmed in the animal model experiments and clinical practice. In addition, application of remedial hepatic stem cells can solve the problems regarding the source, number and immune rejection of hepatocytes, and offers a wide prospect for treatment of acute and chronic liver diseases. There are many problems about the study on hepatic stem cells. Up to date, many manuscripts addressing animal hepatic stem cell transplantation have been found, but few of them focus on the case report of treatment of liver disease by hepatocyte transplantation. Therefore, study on hepatic stem cells is still in its initial stage. The study methods should be developed and improved.

Objective To investigate the expression changes of histidine decarboxylase(HDC)and H+,K+-ATPase in gastric mucosa during the healing of experimental gastric ulcer in rats.Methods The ulcers were caused by applying acetic acid to the serosal surface of the anterior face of the rat gastric body.At different time points during ulcer healing,HDC and H+,K+-ATPase mRNA and protein expressions were studied by using reverse transcription-polymerase chain reaction and Western blot respectively.Results An ulcer crater developed on the anterior face of the gastric body on day 1 after the induction of ulcers,and the ulcer area was biggest on day 3.On day 12,most of the gastric ulcers had healed.Compared with the control group,the HDC and H+,K+-ATPase mRNA expression in the gastric mucosa of ulcer rats showed a decrease on day 1,and increased back to initial level on day 9.The protein expression of HDC and H+,K+-ATPase in gastric mucosa of ulcer rats decreased immediately on day 1,more on day 6,and returned to the initial levels on day 12.Conclusion The mRNA and protein expressions of HDC and H+,K+-ATPase decrease in the healing process of gastric ulcers,resulting in accelerated ulcer healing through inhibiting gastric acid secretion.