Immune checkpoints (ICs) are the core of immunotherapy. Due to the advantages of strong targeting, long-term efficacy and good patient tolerance, immune checkpoint therapy has become a hot spot for the treatment of some major diseases such as malignant tumors. In this paper, the expression and immune mechanism of immunosuppression receptors and immunostimulatory receptors in recent years are summarized, and list the clinical research data of approved drugs targeting immune checkpoint is listed. It provides reference for future research of immune checkpoint and related drugs.

Meroterpenoids are a class of terpenoid-containing hybrid natural products with impressive structures and various bioactivities, which are reflected in antibacterial, anti-inflammatory, anti-tumor and other aspects, and have become a research hotspot in the field of natural products. Here, meroterpenoids isolated from fungi over the past 5 years are summarized. Their chemical structures and biological activities are summarized according to their biosynthetic origin. This review could provide strong support for developing new meroterpenoid-derived drugs.

Transdermal drug delivery is one of the most commonly used clinical drug delivery methods, but it has some limitations such as low skin permeability, short duration of efficacy and low bioavailability. In order to improve the clinical efficacy of drugs and increase patient compliance, the development of lipid nano drug delivery systems for transdermal drug delivery has been favored by researchers. In this paper, the lipid nano drug delivery systems used in transdermal drug delivery systems were summarized in order to provide reference for the clinical application of transdermal drug delivery preparations and the further study of lipid nano drug delivery systems.

OBJECTIVE An efficient and stable HPLC-LTQ-Orbitrap-MS/MS method was developed to analyze and identify the chemical constituents from Tripterospermum chinense (Migo)H.Smith rapidly. METHODS The chemical components in T.chinense were analyzed by high performance liquid chromatography linear ion trap orbital trap tandem mass spectrometry (HPLC-LTQ-Orbitrap-MS/MS). HPLC-LTQ-Orbitrap-MS/MS was used to analyze the chemical components in T.chinense quickly. The accurate molecular weight, reference substance and multistage fragment ion information of the compounds obtained by HPLC-LTQ-Orbitrap-MS/MS scanning, combined with relevant literature and fragmentation regularity, were used to achieve the accurate qualitative analysis of T. chinense. RESULTS A total of 92 chemical constituents were identified, including flavonoids, terpenoids, organic acids, anthraquinones, saccharide, ester and the others. Among them, compounds 3, 4-di-O-caffeoylquinic acid、(2S, 3S, 4S, 5R, 6S)-6-[2-(3, 4-dihydroxyphenyl)-5-hydroxy-4-oxochromen-7-yl]oxy-3, 4, 5-trihydroxyoxane-2-carboxylic acid、(1S, 4aS, 7S, 7aS)-1-[(2S, 3R, 4S, 5S, 6R)-6-[[(E)-3-(3, 4-dihydroxyphenyl)prop-2-enoyl]oxymethyl]-3, 4, 5-trihydroxyoxan-2-yl]oxy-7-hydroxy-7-methyl-4a, 5, 6, 7a-tetrahydro-1H-cyclopenta[c]pyran-4-carboxylic acid and Glc-Glc-octadecatrienoyl-sn-glycerol were identified for the first time in this plant by GNPS database alignment. CONCLUSION A rapid qualitative analysis method of chemical components in T.chinense is established, which provides a scientific basis for the extraction and isolation of the chemical constituents of T.chinense and its pharmacodynamic material basis, and provides a certain reference significance for its quality evaluation and application development.

OBJECTIVE To compare the differences in the chemical compositionof Succus Bambusae with different processes,analyze the safety of Succus Bambusae produced by dry distillation from theperspectives of acuteand subacute toxiciy and provide data support for the further improvement ofthe process standardization andquality standards ofthe large variety offresh bamboo distillate. METHODS Using GC-MS method, combined with PCA and OPLS-DA mathematical algorithms, the differential components and unique components among the three processes were analyzed, and the HPLC method was used to quantitatively analyze the indicators related to toxicity potential. Toxic potential was assessed using a combined acute and subacute toxicity protocol. RESULTS Relative content and substance types have changed significantly, total of 47 components were identified from different processes of Succus Bambusae, including 16 phenols, 11 ketones, 9 esters, 7 aldehydes, 3 carboxylic acids, and 1 alcohol. The results of quantitative analysis of phenol and guaiacol showed that only phenol and guaiacol were detected in the dry distillation process, and the contents were (0.097±0.004) and (0.150±0.017)mg·mL^-1 respectively. The results of acute toxicity test showed that dry distillation of Succus Bambusae decoction had adverse effects on the body weight and gastrointestinal tract of mice. The subacute toxicity test results are consistent with the acute toxicity test results. The high-dose group of dry-distilled Succus Bambusae had adverse effects on the gastrointestinal tract tissue, and the organ indexes of heart, liver, lung and kidney were also significantly increased, but no adverse effects appeared in the low-dose and middle-dose groups. CONCLUSION The huge difference in the material basis of dry distillation Succus Bambusae does have safety risks, and the correlation analysis shows that the risk factors are irritating phenolic components such as phenol and guaiacol. However, the safety evaluation indicates that dry distillation of Succus Bambusae is generally safer. This paper could provide toxicological data support for the clinical application of Succus Bambusae and its preparations.

OBJECTIVE To investigate the effect of tangeretin (TAN) on neuronal pyroptosis in rats with cerebral ischemia/reperfusion injury (CIRI) and its mechanism. METHODS The CIRI model of rats was established by reperfusion after occlusion of the middle cerebral artery for 2 h using thread occlusion method. Experiment 1: SD rats were randomly divided into sham group, CIRI group, TAN-5 mg·kg^-1, TAN-10 mg·kg^-1, TAN-20 mg·kg^-1, and positive control edaravone group (EDA-10 mg·kg^-1), with 10 rats in each group. The rats in each group were subjected to index detection and pathological sampling 24 hours after reperfusion. Zea Longa method was used to score neurological deficits; the rate of cerebral infarction was detected using the 2,3,5-triphenyl tetrazolium chloride (TTC) method; hematoxylin eosin (HE) staining was used to observe the morphology and structure of brain tissue, and the optimal dosage of TAN was selected; propidium iodide staining (PI) was used to detect the ratio of neuronal focal death; immunofluorescence double staining was used to detect the positive expression rate of LC3-Ⅱ in neurons; Western blot was performed for detection of the expressions of pyroptosis-related proteins, PI3K/Akt pathway-related proteins, and autophagy-related proteins (LC3-Ⅱ/LC3-Ⅰ, p62) in brain tissue. Experiment 2: SD rats were randomly divided into sham group, CIRI group, TAN group, and TAN+PI3K inhibitor group (LY294002), with 10 rats in each group. After 24 hours of reperfusion, indicators were tested and pathological samples were taken from each group of rats. Zea Longa method was used to score neurological deficits; TTC staining was used to detect the rate of cerebral infarction; Western blot was used to detect the expressions of pyroptosis-related proteins and autophagy-related proteins in brain tissue. RESULTS Compared with the CIRI group, the neurological deficit score, cerebral infarction volume ratio, and pathological damage to brain tissue of rats in each dose group were reduced. The TAN-20 mg·kg^-1 was selected as the optimal dose group. Compared with the CIRI group, the rate of pyroptosis of neurons was reduced, and the expressions of pyroptosis-related proteins were downregulated, and the positive cell rate of neuron LC3-Ⅱ and the expression of LC3-Ⅱ/LC3-Ⅰ were reduced, the expressions of p-PI3K/PI3K, p-Akt/Akt, and p62 were increased in TAN-20 mg·kg^-1 group. Compared with the TAN-20 mg·kg^-1 group, the PI3K inhibitor LY294002 inhibited the changes in the above indicators and reverse the neuroprotective effect of TAN on CIRI rats. CONCLUSION TAN can inhibit neuronal pyroptosis via regulating PI3K/Akt-mediated autophagy induced by cerebral ischemia-reperfusion.

OBJECTIVE To investigatte antitumor agent epirubicin hydrochloride loaded in TempSLE in vitro/in vivo antitumor activity and provide evidence in clinical use of transcatheter arterial chemoembolization(TACE). METHODS In this study, the TempSLE was selected as the embolic agent, and epirubicin hydrochloride for injection was used as the chemotherapy drug. Epirubicin hydrochloride TempSLE was prepared and its physical and chemical properties and drug release behavior were investigated. Human liver cancer HepG2 cells were selected. The anti-tumor activity of epirubicin hydrochloride TempSLE was evaluated in vitro HepG2 cells. The anti-tumor efficacy of EPI TempSLE in HepG2 tumor-bearing nude mice was evaluated by singly administered EPI TempSLE via peri-tumoral injection. RESULTS The method for preparation of EPI TempSLE was simple; the added EPI did not affect the temperature-sensitive characteristics of TempSLE. The released EPI from EPI TempSLE was about 80% at 24 h time point, after that, EPI was sustained release for 216h and nearly released 100%; the in vitro antitumor activity of EPI TempSLE in HepG2 cells was similar with that of EPI; the in vivo anti-tumor efficacy of EPI TempSLE was observed in HepG2 tumor-bearing nude mice. CONCLUSION The obtained results would help to support the clinical application of epirubicin hydrochloride TempSLE in TACE.

OBJECTIVE To establish a quantitative analysis of multi-components by a single-marker method (QAMS) for simultaneous determination of protocatechuic acid, 3,4-dihydroxybenzaldehyde, caffeic acid, osmundacetone, and hispidin in Sanghuangporus based on HPLC fingerprint analysis of Sanghuangporus samples. METHODS The analysis was performed on an HPLC system equipped with Wondasil C₁₈ Superb column (4.6 nm×250 mm, 5μm), the mobile phase consisted of acetonitrile and 0.1% formic acid solution, and gradient elution procedure was employed. The flow rate was set at 1.0 mL·min^-1, column temperature was maintained at 25℃, and the sample injection volume was 20 μL. The relative correction factors of protocatechuic acid, caffeic acid, osmundacetone and hispidin were calculated with 3,4-dihydroxybenzaldehyde as the internal reference, and the durability of the established method were also investigated. The contents of these five compounds in ten batches of Sanghuangporus from different producing areas or batches were determined by external standard method (ESM) and QAMS method, respectively. RESULTS SPSS, SIMCA and Origin Pro software were employed for principal components assay, similarity evaluation and cluster analysis. The specificity, precision, repeatability, stability and linear range (r²>0.999 0) of the five components were all good. The average recovery was between 99.74%-102.78% and RSD value was between 1.34%-2.92%, respectively. Then 3,4-dihydroxybenzaldehyde was chosen as the internal reference for calculating the correction factors for the other four components, the average relative correction factors of protocatechuic acid, caffeic acid, osmundacetone, and hispidin were 0.851 9, 1.446 9, 1.615 7, and 0.774 7, respectively. Student's t-test results showed that there was no significant difference between the data analyzed by ESM method and the data obtained from QAMS method. Through data visualization analysis, the cluster analysis indicated that samples from Tibet and samples from Guangdong were clustered in significantly different categories. However, there was still one batch Sanghuangporus sample from Guangdong and one batch from Changbai moutains showing more similarities to Tibet category. This indicated that there was a certain relationship between the quality of Sanghuangporus and the origins of Sanghuangporus samples, but there were still other factors affecting the quality of Sanghuangporus such as the confusing species or unclear basic sources. The contents of hispidin, 3,4-dihydroxybenzaldehyde and osmundacetone in different samples showed significant differences, indicating that these three components might be the main quality markers of Sanghuangporus for giving more contributes to the principal components. CONCLUSION Based on HPLC fingerprint, the method of QAMS established in this study is a simple, economical and practical method with scientific and applicable characteristics for evaluating the quality of Sanghuangporus efficiently and scientifically, which can also provide a certain scientific basis for the quality evaluation of its germplasm resources.

OBJECTIVE To observe the inhibitory effect of cordycepin on platelet aggregation and activation induced by different shear rates. METHODS Polydimethylsiloxane (PDMS)-glass microchannel chips were fabricated by soft lithography. The whole blood of normal people anticoagulated with sodium citrate was collected and incubated with different concentrations of cordycepin in vitro, the blood flowed through the straight microchannel or channel with 80% narrow for 150 seconds at the speed of 14.7 μL·min^-1 and 50 μL·min^-1 respectively. The adhesion and aggregation images of fluorescent labeled platelets on glass surface were photographed with the microscope, and the fluorescent images were analyzed with Image J. The platelet surface coverage percent was used as a quantitative index of platelet aggregation behavior. The effect of cordycepin on platelet calcium mobilization and monocyte-platelet aggregate(MPA) was analyzed by flow cytometry. The risk of cordycepin was assessed through test of blood coagulation. RESULTS Cordycepin inhibits platelet aggregation and the inhibition effect is related to the shear rates. At 14.7 and 50 μL·min^-1, platelet aggregation can be inhibited by cordycepin. Cordycepin inhibits platelet calcium mobilization and MPA effectively. It has no effect on exogenous and endogenous coagulation pathways. CONCLUSION Cordycepin can effectively inhibit shear-induced platelet aggregation and is a potential antiplatelet drug.

OBJECTIVE To review the latest progress of phage therapy in clinical application of multiple multidrug-resistant bacterial pneumonia, in order to provide documentary evidence for the application of phage in pulmonary infection. METHODS The keywords “phage” or “phage therapy” or “phage endolysin” or “engineered phage” and “pneumonia” were used in literature search on CNKI and pubmed, and the retrieved case reports were reviewed according to pathogen classification. RESULTS Clinical studies on randomized controlled trial(RCT) of phage therapy for the treatment of pneumonia had not been publicly reported, but phage had achieved good efficacy in the treatment of pneumonia infected by Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae and Acinetobacter baumannii, and only one adverse reaction had been reported. At the same time, this paper discussed the current difficulties of bacteriophage therapy, such as bacterial resistance, its own safety or the influence of immune system on its efficacy, and the latest development direction of phage endolysin and engineered phage therapy. CONCLUSION Bacteriophages have a promising future in the treatment of respiratory infections, especially those caused by multidrug-resistant bacteria. In the future, more in vivo studies may be needed to answer questions about the efficacy and safety of phage derivatives or engineered phage therapy.

OBJECTIVE To evaluate the capacity of laboratories which participate in the proficiency testing of antigen content inactived COVID-19 vaccines. METHODS Samples of inactived COVID-19 vaccines for proficiency testing were tested for uniformity and stability, and was distributed together with reference and test kits to participating laboratories by cold chain transportation. Three indexes were evaluated: differential test, antigen content detection and laboratory variation. RESULTS The uniformity and stability of the proficiency test samples met the requirements. A total of 14 laboratories participated in this proficiency test and reported the results as required, and the assessment results of three indicators by each laboratory all satisfactory. CONCLUSION China's provincial drug testing institutions and inactivated vaccine manufacturers participating in this proficiency test have good detection capabilities and quality control levels for inactived COVID-19 vaccines.