Tumor microenvironment(TME)is the cellular environment for tumor development,growth,and metastasis.Adenosine(ADO)is an immunosuppressive metabolic product that is continuously upregulated in TME,with various types and wide distribution of receptors.The complex and dynamic interactions between ADO and tumor cells constantly influence tumor progression.ADO can di-rectly or indirectly promote tumor development and progression by promoting tumor generation and metastasis,mediating the immune escape of tumor,and modulating tumor-infiltrating immune cells.Based on the characteristics of ADOs in TME,this article reviews the latest advances in the dynamic alterations of ADO in TME,in order to provide insights into tumor treatment targeting the ADO pathway.

Cholesterol,as an important component of cell membranes,plays a multifaceted role in mediating tumor immunomodulation and drug intervention.In case of cholesterol metabolic imbalance,the accumulation of cholesterol metabolic intermediates,the changes in concentrations,and the regulation of related signaling pathways can affect tumor immunity by promoting inflammation and inhibiting immune cell function.Preclinical and clinical studies have shown that controlling cholesterol metabolism can inhibit tumor growth,re-shape body immune regulation,and enhance antitumor immunity.A deep understanding of the association between immune cells and cholesterol metabolic pathways in the tumor microenvironment can help to develop novel drugs targeting cholesterol metabolism.This article reviews the multifaceted role of cholesterol and its derived metabolites in the tumor microenvironment by regulating various types of immune cells such as myeloid-derived suppressor cells,tumor-associated macrophages,dendritic cells,and T-lymphocytes,as well as the characteristics of tumor immunomodulation mediated by cholesterol metabolism and the advances in pharmaceutical re-search on improving the immune function of the body by intervening against cholesterol,in order to further provide new ideas and a thera-peutic basis for cholesterol modulation and intervention in tumor im-munotherapy.

Pulmonary disease is one of the major threats to human health. However, the current clinical treatment drugs for lung diseases generally have problems such as low lung delivery efficiency, fast clearance rate and obvious toxic side effects. Recently, membrane biomimetic nanocarriers have attracted more and more attention. Due to their advantages of high targeting, long cycle time, good biocompatibility and strong immune escape ability, membrane biomimetic nanocarriers have become a major research hotspot in targeted therapy of lung diseases. In this review, we discuss the main preparation methods of membrane biomimetic nanoparticles, the characteristics of membrane biomimetic nanocarriers from different cell sources and their application in the targeted therapy of lung diseases. At the same time, according to the characteristics of different membranes, the shortcomings, current technical limitations and future prospects are discussed. This review is expected to provide references for the design of membrane biomimetic nanocarriers and their potential applications in the treatment of lung diseases.

Objective The diagnostic efficacy of the two gene methylation indexes was verified by lung biopsy or postoperative disease examination results.Methods A prospective study was conducted to collect 99 patients diagnosed with pulmonary nodules and masses in the Third People's Hospital of Yunnan Province from March 2019 to March 2020.After bronchoscopy and BALF samples were collected,regular follow-up,lung puncture biopsy and post-operative disease examination were performed.Results Ninety-nine patients with pulmonary nodules and masses were divided into lung cancer group(n = 50)and benign lung disease group(n = 49)after pathological diagnosis.The age of patients in the lung cancer group was(62.64±9.71)years,and that of the benign lung disease group was(60.48±13.69)years,and there was a statistical difference between the two groups(P = 0.032).In the diagnosis of lung cancer,the sensitivity and specificity of SHOX2 and RASSF1A genes alone were found to be 72%and 58%,respectively,and 92.3%and 95.9%,respectively.The combined test of the two genes showed a higher sensitivity in the diagnosis of lung cancer,0.84,compared to 0.102 in the benign disease group(P<0.001).ROC curve analysis showed that the sensitivity of the two genes could be increased to 84%when methylation was combined.Conclusion The methylation test of SHOX2 and RASS1A gene in alveolar lavage fluid has a good value in the diagnosis of lung cancer patients with pulmonary nodules and masses and SHOX2 combined with RASSF1A can be an important supplementary tool for early diagnosis of lung cancer when imaging and histological diagnosis are unclear.

WS9326A is a peptide antibiotic containing a highly unusual N-methyl-E-2-3-dehydrotyrosine (NMet-Dht) residue that is incorporated during peptide assembly on a non-ribosomal peptide synthetase (NRPS). The cytochrome P450 encoded by sas16 (P450_Sas) has been shown to be essential for the formation of the alkene moiety in NMet-Dht, but the timing and mechanism of the P450_Sas-mediated α,β-dehydrogenation of Dht remained unclear. Here, we show that the substrate of P450_Sas is the NRPS-associated peptidyl carrier protein (PCP)-bound dipeptide intermediate (Z)-2-pent-1'-enyl-cinnamoyl-Thr-N-Me-Tyr. We demonstrate that P450_Sas-mediated incorporation of the double bond follows N-methylation of the Tyr by the N-methyl transferase domain found within the NRPS, and further that P450_Sas appears to be specific for substrates containing the (Z)-2-pent-1'-enyl-cinnamoyl group. A crystal structure of P450_Sas reveals differences between P450_Sas and other P450s involved in the modification of NRPS-associated substrates, including the substitution of the canonical active site alcohol residue with a phenylalanine (F250), which in turn is critical to P450_Sas activity and WS9326A biosynthesis. Together, our results suggest that P450_Sas catalyses the direct dehydrogenation of the NRPS-bound dipeptide substrate, thus expanding the repertoire of P450 enzymes that can be used to produce biologically active peptides.

Objective To investigate the efficacy and safety of enhanced recovery after surgery (ERAS) in the perioperative period of pancreaticoduodenectomy (PD). Methods Chinese and English databases were searched for controlled clinical trials on the application of ERAS in PD published from 2000 to 2021. Screening, quality assessment, and data extraction were performed for the articles, and RevMan5.3 software was used for meta-analysis. This study was registered on PROSPERO with a registration number of CRD42021287931. Results A total of 22 controlled clinical trials were included, with 3531 patients in total. The results showed that the implementation of ERAS in the perioperative period of PD reduced the incidence rates of total complications (odds ratio [ OR ]=0.63, 95% confidence interval [ CI ]: 0.48-0.83, P =0.001), abdominal infection ( OR =0.65, 95% CI : 0.47-0.88, P =0.005), pulmonary complications ( OR =0.57, 95% CI : 0.42-0.78, P =0.000 5), pancreatic leakage ( OR =0.80, 95% CI : 0.67-0.97, P =0.02), and delayed gastric emptying ( OR =0.58, 95% CI : 0.48-0.71, P < 0.001) and effectively shortened the length of postoperative hospital stay (mean difference=-2.76, 95% CI : -3.36 to -2.16, P < 0.001). However, there were no significant differences between the two groups in mortality rate, incision infection, postoperative bleeding rate, reoperation, and rehospitalization (all P > 0.05). Conclusion ERAS has good efficacy and safety in the perioperative period of PD and can significantly reduce the incidence rates of postoperative complications and shorten the length of postoperative hospital stay. Therefore, it holds promise for clinical application.

Antigens, Neoplasm ; genetics ; Apoprotein(a) ; genetics ; Carrier Proteins ; genetics ; Endometriosis ; metabolism ; pathology ; Endometrium ; metabolism ; pathology ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Membrane Proteins ; genetics ; Mutation, Missense ; genetics ; Nuclear Proteins ; genetics ; Ovarian Neoplasms ; metabolism ; pathology ; Proprotein Convertase 5 ; genetics ; Salivary Cystatins ; genetics ; Ubiquitin-Protein Ligases ; genetics ; Whole Exome Sequencing

BackgroundWhen considering the issue of recurrence, perimenopausal women may have more dilemma during management comparing with young women, for example, whether to retain the uterus and ovary during surgery, whether it is necessary to add adjuvant medicine treatment after operation, and there is no evidence for reference about using of gonadotropin-releasing hormone agonist. This study aimed to study the risk factors for the recurrence of ovarian endometriosis (EM) in patients aged 45 and over.

MethodsThis is a retrospective nested case-control study. We reviewed the medical records of patients aged over 45 years who underwent surgical treatments for ovarian EM from 1994 to 2014, in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences. By following up to January 2016, 45 patients were found to have relapses and regarded as the recurrence group. The patients with no recurrence during the same follow-up period were randomly selected by the ratio of 1:4 as the nonrecurrence group (180 patients in total). Stratified Cox regression was used to analyze the risk factors of the recurrence.

ResultsUnivariate analysis showed that there was a significant difference in the postoperative treatment (the percentage of patients who received postoperative treatment in non-recurrence group and recurrence group, 23.9% vs. 40.0%, χ = 4.729, P = 0.030) and ovarian preservation (the percentage of patients who received surgery of ovarian preservation in non-recurrence group and recurrence group, 25.0 % vs. 44.4%, χ = 19.462, P < 0.001) between the nonrecurrence group and the recurrence group. There was no correlation between recurrence and the following factors including patient's age, menarche age, gravidity, parity, CA125 level, ovarian lesions, menopausal status, combined benign gynecological conditions (such as myoma and adenomyoma) and endometrial abnormalities, and surgical approach or surgical staging (all P > 0.05). Multivariate analysis indicated that whether to retain the ovary was the only independent risk factor of recurrence for patients aged 45 years and over with ovarian EM (odds ratio: 5.594, 95% confidence interval: 1.919-16.310, P = 0.002).

ConclusionOvarian preservation might be the only independent risk factor of recurrence for patients aged 45 years and over with ovarian EM.

Case-Control Studies ; Endometriosis ; epidemiology ; etiology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Odds Ratio ; Ovarian Neoplasms ; epidemiology ; etiology ; Ovary ; pathology ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors

OBJECTIVETo study the expression of C3aR and C5aR in trichloroethylene-sensitized mouse liver injury and discuss the pathogenesis of Dermatitis Medicamentosa-like of TCE (DMLT).

METHODS6∼8 w female BALB/c mouse were randomly divided into blank control group, solvent control group and TCE treatment group. TCE was given to the mouse for sensitization at 1th, 4th, 7th, 10th day and challenge at 17th day and 19th day. Before killing mouse, liver weight and body weight were recorded. The livers were separated at 24 h, 48 h, 72 h and 7 d after challenge. And the liver sections were used for immunofluorescence stain and RT-PCR to detect the expression levels of C3aR and C5aR.

RESULTSMicroscopic examination showed no significant change in liver structure or organization in TCE non-sensitized group, while liver cell oedema, cell necrosis and inflammatory cell infiltration were clearly observed in TCE-sensitized groups. The expression levels of C3aR and C5aR in 24 h, 48 h, 72 h and 7 d TCE-sensitized groups were significant higher than blank control group, solvent control group and related TCE non-sensitized groups (P < 0.05).

CONCLUSIONComplement activation was involved in TCE-induced liver injury and C3aR and C5aR might play essential role in the process.

Animals ; Chemical and Drug Induced Liver Injury ; Dermatitis, Occupational ; Edema ; Female ; Liver ; physiopathology ; Mice ; Mice, Inbred BALB C ; Receptor, Anaphylatoxin C5a ; metabolism ; Receptors, Complement ; metabolism ; Solvents ; toxicity ; Trichloroethylene ; toxicity