Erratum: Author correction to "Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy" Acta Pharm Sin B (2022) 4224-4234

[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Emerging trends in organ-on-a-chip systems for drug screening

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.

Sequential delivery of PD-1/PD-L1 blockade peptide and IDO inhibitor for immunosuppressive microenvironment remodeling via an MMP-2 responsive dual-targeting liposome

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

Investigation and Analysis of the Implementation Status and Effect of Electronic Prescription and Remote Pharma- ceutical Care in Social Pharmacy from the Perspective of Consumers / 中国药房

OBJECTIVE：To evaluate the current situation and implementation effect of the pilot project of electronic prescription and remote pharmaceutical care in social pharmacy from the perspective of consumers ，and to provide reference for improving and optimizating the electronic prescription and remote pharmaceutical care in social pharmacy. METHODS ：Totally 264 consumers in 6 counties and 36 drugstores of Chengdu were randomly selected for the questionnaire survey. Descriptive statistics were conducted by using SPSS 23.0 software. Compare the distribution and differences of various. The influential factors in consumer satisfaction based on χ2 test and ordinal multiple Logistic regression analysis. Consumers were randomly selected for semi-structured interviews. Text analysis was conducted by Nvivo 12.0 software to refine the problem of this service . RESULTS ：A total of 271 questionnaires were distributed to consumers in various districts of Chengdu ，and 264 valid questionnaires were collected，with an effective recovery rate of 97.4％. Among 264 respondents，178（67.9％）knew about electronic prescription and remote pharmaceutical care ；197（74.6％）received electronic prescription and remote pharmaceutical care service in pharmacies ； 202（76.5％）said they needed this service ，and 63（23.9％）expressed that they would like to pay for it. Of the 197 respondents who had received the service ，163（82.2％）were satisfied or very satisfied with the service ，and only one （0.5％）was dissatisfied with the service. Waiting time ，satisfaction of drug demand ，staff attitude ，service platform configuration ，the qualifications of tele-practice pharmacists and service quality were the main influential factors of satisfaction ；while the service also suffered from difficulties in electronic prescription circulation ，inadequate service monitoring measures ，insufficient certification of physicians and pharmacists，cultural lag ，and irregular service processes. CONCLUSIONS ：Electronic prescription and remote pharmaceutical care service in social pharmacy is inadequate in terms of technical level ，institutional design and social acceptance. It is recommended that relevant departments implement incentive policies ，optimize technology ；follow up supporting policies in time ，strengthen supervision；and increase social publicity and supervision ，so as to promote the continuous improvement and long-term development of electronic prescription and remote pharmaceutical care in social pharmacy.

Recent advances of microneedles for biomedical applications: drug delivery and beyond

The microneedle (MN), a highly efficient and versatile device, has attracted extensive scientific and industrial interests in the past decades due to prominent properties including painless penetration, low cost, excellent therapeutic efficacy, and relative safety. The robust microneedle enabling transdermal delivery has a paramount potential to create advanced functional devices with superior nature for biomedical applications. In this review, a great effort has been made to summarize the advance of microneedles including their materials and latest fabrication method, such as three-dimensional printing (3DP). Importantly, a variety of representative biomedical applications of microneedles such as disease treatment, immunobiological administration, disease diagnosis and cosmetic field, are highlighted in detail. At last, conclusions and future perspectives for development of advanced microneedles in biomedical fields have been discussed systematically. Taken together, as an emerging tool, microneedles have showed profound promise for biomedical applications.

Long term follow-up and prognostic analysis of 85 cases with primary gastrointestinal diffuse large B cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics, prognostic factors in patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL).</p><p><b>METHODS</b>Long term follow-up of 85 patients with PGI-DLBCL was carried out and the patients clinical data were retrospectively evaluated. The risk factors for survival rate were analyzed by univariate and multivariate Cox regression analysis.</p><p><b>RESULTS</b>The median age of 85 patients was 61 years old (18-87), and male: female ratio was 1.83:1 (55/30). The stomach origin accounted for 63.5% (54/85), intestine origin for 35.3% (30/85) and multiple GI involvements for 1.2% (1/85). Bone marrow involvement accounted for 16.4% (11/64), Helicobacter pylori (HP) infection for 51.4% (19/37). The 5-year overall survival (OS) rates of all patients were 63.9%. The 5-year OS of patients in stomach and intestinal groups were 75.3% and 44.1%, respectively (P=0.005). The 5-year OS of germinal center B cell-like (GCB) group and non-GCB groups were 64.7% and 62.4%, respectively (P = 0.610). Univariated analysis revealed that the factors affecting OS of patients included age, lesion site, tumor size, gastrointestinal clinical Lugano staging system, IPI score (all P values < 0.05). Multivariate Cox regression analysis revealed that IPI score was independent prognosis risk factor affecting OS (RR = 3.609, 95 CI 2.034-6.404, P < 0.01).</p><p><b>CONCLUSION</b>IPI score was independent prognosis risk factor affecting OS of PGI-DLBCL patients.</p>

Effect of donor-specific immature dendritic cells infusion in combination with CsA on differentiation of liver recipient′s Th1/Th2 cell in rats / 中国普通外科杂志

Objective To investigate the effect of donor specific immature dendritic cells infusion in combination with CsA on differentiation of liver recipient′s Th1/Th2 cell in rats. Methods Allograft models of orthotopic rat liver transplantation were established, 88 LEW rats (recipient) and SD rats (donor) were randomly divided into three groups: (1) in control group no immunosuppresive drug was used after liver transplantation. (2) in CsA group 1 mg/100 g body weight of CsA was injected intraperitoneally every the other day for 3 times beginning the 2nd day after liver transplantation. (3) in CsA+DC group additional 1? 10 6 immature DC from donor bone marrow was injected through penile vein at the 8th day after operation, in combination with CsA as in CsA group. Rats were sacrificed for immunopathological examination and detection of INF ?mRNA, IL 6 mRNA of celiac lymph node on 5th, 10th, 15th, and 25th day after transplantation. Results The average recipient survival time in the CsA+DC group was (27 0?1 0) days, significantly longer than that in control and CsA group (all P